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The Classics Series™ | The Classics in Medicine™: Summaries of the Landmark Trials: Online Edition | All Specialties
The Classics Series™ by 2 Minute Medicine is the original and most comprehensive collection of journal landmark trials, summarized by doctors. Since 2012, we have been curating and summarizing the most impactful new and historical landmark trials. In the span of the last 35 years, the evolution from print to digital platforms has catalyzed an immense growth in medical literature. Addressing this surge, 2 Minute Medicine delivers an enhanced and authoritative compilation of physician-authored summaries, capturing the essence of more than 300 pivotal medical trials in this wiki, with continual updates. A deep understanding of these trials is paramount for every physician, healthcare professional, and trainee, as it lays the foundation for evidence-based clinical decisions made daily.
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| Title | Year | Journal | Citations | Key findings |
|---|---|---|---|---|
| The UKPDS: Reducing the risk of diabetes-related morbidity and mortality | 1998 | Lancet | 20,000 | 1. For patients with type 2 diabetes mellitus, pharmacologic blood glucose control with sulfonylureas or insulin significantly reduces the risk of microvascular complications, but not macrovascular complications 2. Metformin therapy is associated with significant reductions in diabetes-related and all-cause mortality; thus, it is considered first-line therapy for type 2 diabetes mellitus 3. Strict control of blood pressure in type 2 diabetes mellitus reduces the risk of both microvascular and macrovascular complications, along with diabetes-related mortality |
| The Women’s Health Initiative: Risks outweigh benefits of combination hormone replacement therapy | 2002 | JAMA | 10365 | 1. Combination estrogen and progestin hormone replacement therapy (HRT) is associated with a 29% increased risk of cardiovascular disease, 110% increased risk of venous thromboembolism and 26% increased risk of invasive breast cancer. 2. Over 1 year, 10 000 women taking combination HRT might experience 7 more cardiovascular events, 8 more strokes, 8 more pulmonary emboli, 8 more cases of invasive breast cancer, 6 fewer colorectal cancers and 5 fewer hip fractures. |
| The HOT trial: Diastolic blood pressure targets in hypertension | 1998 | Lancet | 7133 | 1. In hypertensive patients, there were no significant differences between different diastolic blood pressure (dBP) targets (≤90 mmHg,≤85 mmHg,≤80 mmHg) with regards to the risk of major cardiovascular events. 2. In patients with diabetes, treating to a target ≤80 mmHg led to significantly fewer major cardiovascular events and cardiovascular death compared to those treated to a target ≤90 mmHg. 3. Antihypertensive therapies were generally well tolerated, with common complaints including dizziness, leg edema, and coughing. |
| The CARE trial: Statins in coronary artery disease | 1996 | NEJM | 6321 | 1. Cholesterol-lowering therapy with statins reduces the risk of coronary events and stroke in patients with previous coronary artery disease and low-density lipoprotein levels >125 mg/dL 2. The reduction in coronary events with statin therapy was greater in women and patients with higher pre-treatment levels of cholesterol |
| The RENAAL Trial: Losartan in diabetic nephropathy | 2001 | NEJM | 5646 | 1. In patients with type II diabetes and nephropathy, losartan at a dose of 50-100 mg daily significantly reduced the risk of developing end-stage renal disease compared to placebo 2. While losartan also significantly reduced the degree of proteinuria in these patients, it did not significantly reduce mortality when compared with placebo |
| The Rivers trial: Early goal-directed therapy in severe sepsis and septic shock | 2001 | NEJM | 5603 | 1.Early goal-directed therapy in patients with severe sepsis and septic shock prior to admission to the intensive care unit significantly reduces organ dysfunction and mortality rates compared to standard therapy to achieve parameters for hemodynamic support |
| The SCD-HeFT: ICD vs. amiodarone for congestive heart failure | 2005 | NEJM | 5343 | 1. In patients with congestive heart failure (CHF) and reduced ejection fraction, mortality was significantly lower in patients who received an implantable cardioverter-defibrillator (ICD) compared those who did not receive one. 2. In these patients, amiodarone did not confer a favorable survival benefit as compared to placebo. |
| The RALES trial: Spironolactone decreases all-cause mortality in heart failure patients | 1999 | NEJM | 5191 | 1.Adding 25 mg of spironolactone to standard therapy reduces all-cause mortality in heart failure patients with an ejection fraction <35% |
| The HOPE trial: Ramipril significantly reduces cardiovascular events in high-risk patients with normal ejection fractions | 2000 | NEJM | 5150 | 1.Ramipril significantly reduces cardiovascular events including MI, stroke and death in high risk-patients in the absence of left ventricular dysfunction |
| The CONSENSUS: Enalapril reduces mortality in severe heart failure | 1987 | NEJM | 4909 | 1. In patients with severe heart failure, treatment with enalapril significantly reduced the risk of mortality at 6-months and 1-year when compared with placebo. 2. The reduction in mortality was due to significantly lower risk of mortality resulting from progression of heart failure. 3. Patients on enalapril were significantly more likely to suffer from hypotension compared to those receiving placebo. |
| The Child-Pugh score: Prognosis in chronic liver disease and cirrhosis | 1973 | British Journal of Surgery | 4623 | 1. The Child-Pugh score consists of five clinical features and is used to assess the prognosis of chronic liver disease and cirrhosis 2. The Child-Pugh score was originally developed in 1973 to predict surgical outcomes in patients presenting with bleeding esophageal varices 3. The score is used with the Model for End-Stage Liver Disease (MELD) to determine priority for liver transplantation |
| Angiotensin-receptor blockers in diabetic nephropathy | 2001 | NEJM | 4619 | 1. Irbesartan was associated with a significantly lower risk of doubling of serum creatinine concentration, developing end-stage renal disease, or death from all causes 2. Serum creatinine concentration increased at a slower rate in patients receiving irbesartan compared to amlodipine and placebo groups |
| The SAVE trial: Captopril after acute MI reduces mortality and morbidity | 1992 | NEJM | 4410 | 1.Treating patients with captopril after acute MI with asymptomatic LV dysfunction reduces mortality from cardiovascular causes (i.e., atherosclerotic heart disease, progressive heart failure) 2.The captopril group experienced lower rates of hospitalization due to heart failure and recurrent MI |
| Zidovudine reduces maternal-infant HIV transmission | 1994 | NEJM | 3931 | 1. Among pregnant women with HIV, antepartum, intrapartum and neonatal zidovudine therapy reduced maternal-fetal transmission of HIV by two-thirds. |
| The HMPS I: Adverse events in patients and negligence | 1991 | NEJM | 3800 | 1.It was found that adverse events occurred in 3.7% of hospitalizations 2.Approximately 27.6% of adverse events occurring in hospital were attributed to negligence |
| The OHTS trial: Topical ocular hypotensive medication reduces risk of open-angle glaucoma | 2002 | Archives of Opthalmology | 3684 | 1. At 5 years, the probability of developing open-angle glaucoma was significantly lower in the group that received topical ocular hypotensive medication compared to the observed group 2. Older age, male gender, African-American ethnicity, larger cup-to-disc ratios, higher IOP, greater visual field deficits, heart disease, and reduced cornea thickness were predictors of the development of glaucoma |
| The TNT trial: Intensive statin therapy in coronary heart disease | 2005 | NEJM | 3606 | 1. In patients with stable coronary heart disease (CHD), high-dose atorvastatin significantly reduced the risk of major cardiovascular events when compared to low-dose. 2. Patients in the high-dose group experienced significantly higher rates of adverse events, though the rate of statin-related myalgias were similar in the two groups. |
| The DASH trial: Diet change significantly reduces blood pressure | 1997 | NEJM | 3477 | 1. A “combination” diet rich in fruits and vegetables and low in saturated and total fat reduces blood pressure in comparison to the typical American diet 2. Blood-pressure reductions were observed in the setting of stable weight, unchanged sodium intake, and consumption of no more than two alcoholic drinks per day |
| The MADIT-II: Prophylactic defibrillator improves survival in patients with myocardial infarction and left ventricular dysfunction | 2002 | NEJM | 3319 | 1.This trial found a 31% reduction in risk of death associated with implantation of a defibrillator compared to conventional therapy 2.Rates of hospitalization with heart failure were somewhat higher in the defibrillator group, though this did not reach significance |
| The PROVE IT trial: High-dose statin regimen reduces mortality after ACS | 2004 | NEJM | 2932 | 1. High-dose atorvastatin was associated with a 16% reduction in death or major cardiovascular events compared to standard pravastatin therapy following an acute coronary syndrome 2. The protective effect of intensive lipid-lowering was evident in the first 30 days of therapy and was consistent across pre-specified subgroups |
| The HMPS II: Characterizing adverse events in hospitalized patients | 1991 | NEJM | 2914 | 1. Drug-related complications were the most common type of adverse event in hospitalized patients 2. Adverse events due to negligence in hospitalized patients were more likely to cause serious disability or death than adverse events not attributed to negligence |
| The CURE trial: Clopidogrel in ACS without ST-elevation | 2001 | NEJM | 2911 | 1.The addition of clopidogrel significantly reduced the risk of death from cardiovascular causes, nonfatal myocardial infarction, or other ischemic events in patients with ACS without ST elevation2.Adding clopidogrel is associated with significantly higher risk of major and minor bleeding, but not life-threatening bleeding |
| Periconceptional folic acid for prevention of neural tube defects | 1992 | NEJM | 2875 | 1. Among women seeking pregnancy, those randomized to folic acid supplementation were significantly less likely to develop a fetus with a neural tube defect. |
| The EPHESUS trial: Eplerenone in heart failure after myocardial infarction | 2003 | NEJM | 2875 | 1. Eplerenone significantly reduces all-cause mortality in patients with heart failure and left ventricular dysfunction (LVEF≤40%) after myocardial infarction when compared with placebo 2. Eplerenone treatment in this setting also significantly reduced mortality from cardiovascular causes and hospitalizations for cardiovascular issues |
| V-HeFT II: Enalapril reduces mortality in heart failure when compared to hydralazine and isosorbide | 1991 | NEJM | 2836 | 1. In patients with heart failure, patients treated with enalapril experienced significantly lower mortality at 2-years compared to patients on hydralazine and isosorbide dinitrate. 2. Patients treated with enalapril experienced significantly higher serum creatinine levels and higher potassium levels than patients on the combination of hydralazine and isosorbide dinitrate. |
| The CATIE trial: High rates of medication discontinuation in schizophrenic patients | 2005 | NEJM | 2832 | 1. Approximately 74% of schizophrenic patients discontinued their medications before 18 months, with the median being approximately 6 months 2. Olanzapine was found to have a significantly longer time to discontinuation than quetiapine and risperidone 3. Olanzapine was associated with significantly more weight gain and increases in glycosylated hemoglobin, cholesterol, and triglycerides when compared to the other antipsychotics |
| The TRITON trial: Prasugrel vs clopidogrel in ACS | 2007 | NEJM | 2793 | 1. Prasugrel was more effective than clopidogrel in reducing the incidence of recurrent myocardial infarction in patients presenting with acute coronary syndrome, though there was no difference in mortality between the two groups 2. Patients treated with prasugrel had a significantly higher incidence of fatal major bleeding compared to clopidogrel |
| The REMATCH trial: Left ventricular assist devices reduce mortality in heart failure | 2001 | NEJM | 2762 | 1. In patients with end-stage heart failure on optimal medical therapy, treatment with a left ventricular assist device (LVAD) significantly reduced the risk of all-cause mortality when compared with medical therapy alone. 2. The difference in mortality was observed at 1 year, while no significant differences were observed at the 2-year mark. |
| Delayed antimicrobial therapy linked with higher mortality in septic shock | 2006 | Critical Care Medicine | 2676 | 1. Septic shock is a complication of infection with very high mortality rates. 2. This study was one of the first to demonstrate that delaying the provision of effective antimicrobial therapy in septic shock leads to significantly higher mortality rates. |
| No difference in long-term survival after breast-conserving surgery compared to mastectomy | 2002 | NEJM | 2671 | 1.In women with stage I or II breast cancer, there was no significant difference in overall survival in women treated with total mastectomy compared to breast-conserving surgery 2.Adjuvant radiation therapy was associated with reduced ipsilateral recurrence in lumpectomy-treated women |
| Voriconazole superior to amphotericin B for invasive aspergillosis | 2002 | NEJM | 2631 | 1. In immunocompromised patients with invasive aspergillosis, treatment with voriconazole was found to be superior to amphotericin B in achieving successful outcomes. 2. The incidence of serious adverse events was significantly lower in patients in the voriconazole group, as compared with those in the amphotericin B group. |
| The TRICC trial: Restrictive transfusion in intensive care does not increase mortality | 1999 | NEJM | 2625 | 1. Using a restrictive transfusion strategy in critically ill patients did not significantly increase 30-day mortality when compared with a liberal transfusion strategy 2. Subgroup analyses demonstrated that a restrictive transfusion strategy was associated with significantly lower mortality in patients with APACHE II score ≤20 and age <55 years |
| The JUPITER trial: Rosuvastatin decreases the rate of cardiovascular events in healthy men and women with elevated CRP levels | 2008 | NEJM | 2611 | 1.Rosuvastatin significantly decreased the incidence of a first major cardiovascular event compared to placebo 2.Rosuvastatin also significantly decreased the risk of all cause mortality by 20% compared to placebo |
| The Val-HeFT trial: Valsartan reduces morbidity in chronic heart failure | 2001 | NEJM | 2578 | 1. Valsartan, an angiotensin-receptor blocker, significantly reduces morbidity, but not mortality, in heart failure patients when added to background therapy 2. As an exception, valsartan was associated with increased morbidity and mortality in patients already receiving both an angiotensin-converting-enzyme inhibitor and beta-blocker |
| The MERIT-HF trial: Addition of metoprolol reduces mortality in patients with symptomatic heart failure | 1999 | Lancet | 2533 | 1.In patients with symptomatic heart failure and reduced ejection fraction, the addition of metoprolol to standard therapy reduced all-cause mortality by 34% compared to placebo 2.Similar findings were reported by the CIBIS-II trial |
| The MELD score: Predicting survival in end-stage liver disease | 2001 | Hepatology | 2376 | 1. The Model for End-Stage Liver Disease (MELD) is a reliable tool for predicting short-term survival in patients with advanced liver disease 2. The score is generalizable to diverse etiologies and a wide range of disease severity |
| The RELY trial: Dabigatran non-inferior to warfarin in preventing strokes in patients with atrial fibrillation | 2009 | NEJM | 2285 | 1.High-dose dabigatran is superior to warfarin in the prevention of strokes in patients with atrial fibrillation, while low-dose dabigatran is non-inferior to warfarin in preventing strokes in this population 2.There is lower risk of major hemorrhage on low-dose dabigatran compared to warfarin, while there is similar rate of major hemorrhage on high-dose dabigatran as compared to warfarin |
| Nurses’ Health Study: Estrogen associated with lower cardiovascular disease risk | 1991 | NEJM | 2283 | 1. Healthy postmenopausal nurses aged 30-53 years on estrogen therapy had a 44% reduced risk of major coronary disease compared to women not on estrogen. 2. Age-adjusted relative risk of cardiovascular mortality for postmenopausal women on estrogen was 0.72 (CI: 0.55-0.95, p=0.02). |
| The V-HeFT I: Hydralazine and isosorbide dinitrate in heart failure | 1986 | NEJM | 2264 | 1. In patients with congestive heart failure, the combination of hydralazine and isosorbide dinitrate significantly reduced mortality when compared with placebo. 2. This was one of the first large, randomized trials to demonstrate significant mortality benefit in the treatment of congestive heart failure. |
| The AREDS1: Zinc and antioxidant supplementation reduce progression of AMD in high-risk patients | 2001 | JAMA Ophthalmology | 2262 | 1. In patients with advanced age-related macular degeneration (AMD) in one eye only or intermediate AMD in either eye, zinc and antioxidant supplementation reduced the risk of progression to advanced AMD and reduced the risk of moderate vision loss. 2. In patients with early stage AMD, supplementation did not reduce the risk of progressing to advanced AMD. No supplementation is recommended in early stage AMD, as the baseline risk of progression is low. |
| The Bogalusa Heart Study: Childhood weight status and cardiovascular risk factors | 1999 | Pediatrics | 2199 | 1. Children recruited for weight and cardiovascular risk assessment were found to have higher frequencies of cardiac risks factors as their BMIs increased 2. Among the cardiovascular risk factors assessed, overweight youth had the highest odds of having elevated insulin levels |
| The ACCORD trial: Intensive glucose control associated with increased mortality | 2008 | NEJM | 2187 | 1. Previous studies suggest that intensive blood glucose control reduces the risk of microvascular complications, though questions remained regarding the impact on macrovascular complications and mortality 2. This study found that targeting HbA1c <6.0% resulted in higher risk of cardiovascular and all-cause mortality as compared with standard therapy (i.e., targeting hba1c between 7.0-7.9%) |
| The TORCH Trial: Combination of salmeterol and fluticasone in treating COPD | 2007 | NEJM | 2148 | 1. The combination of salmeterol and fluticasone did not significantly reduce all-cause mortality in patients with chronic pulmonary obstructive disease (COPD) 2. When compared with salmeterol alone, fluticasone alone, and placebo, combination therapy significantly reduced the risk of exacerbations and the need for systemic corticosteroids during exacerbations |
| Finasteride significantly reduces incidence of prostate cancer | 2003 | NEJM | 2141 | 1. Finasteride therapy was found to significantly reduce the incidence of prostate cancer compared to placebo 2. Patients treated with finasteride were significantly more likely to have high-grade prostate cancers 3. Patients on finasteride experienced significantly higher rates of sexual side effects, included erectile dysfunction, loss of libido, and gynecomastia |
| Experimental gene therapy results in full clinical reversal of X-linked SCID | 2000 | Science | 2111 | 1. Two patients with X-linked severe combined immunodeficiency were treated with a retroviral-vector containing γc receptor for IL-2 with full clinical reversal after ten months 2. No side effects were reported during the study period |
| The ALLHAT: Thiazide diuretics as first-line antihypertensive therapy | 2002 | JAMA | 2097 | 1. There were no significant differences in the rates of fatal coronary heart disease or nonfatal myocardial infarction when comparing thiazide diuretics with ACE-Is or CCBs in hypertension management 2. Thiazide diuretics are the cheapest option amongst common first-line antihypertensives |
| Antenatal steroids for fetal lung maturity | 1972 | Pediatrics | 2075 | 1. Respiratory distress syndrome (RDS) and perinatal mortality were significantly less common among preterm infants whose mothers received betamethasone prior to delivery. |
| The AVERROES trial: Apixaban vs aspirin in atrial fibrillation | 2011 | NEJM | 1989 | 1. In patients with atrial fibrillation who were unable to receive warfarin for any reason, the use of apixaban reduced the risk of stroke and systemic embolism when compared to aspirin. 2. There were no significant differences between the groups in the risk of major bleeding. |
| The CHADS2 score: Stroke risk in atrial fibrillation | 2001 | JAMA | 1966 | 1.The CHADS2 index is an accurate predictor of stroke in patients with non-rheumatic atrial fibrillation 2.CHADS2 scores can be used to aid decisions regarding the need for anti-thrombotic therapy |
| The CAST trial: Anti-arrhythmic agents increase risk of death in patients after MI | 1991 | NEJM | 1963 | 1.The use of class IC anti-arrhythmic agents flecainide and encainide in patients following myocardial infarction with left ventricular dysfunction increases the risk of death due to arrhythmia and shock |
| The CHARM-Added trial: Adding candesartan to ACE inhibitor reduces mortality in heart failure | 2003 | Lancet | 1929 | 1. Angiotensin-converting-enzyme (ACE) inhibitors had been shown to significantly reduce mortality in patients with heart failure, and it was hypothesized that adding an angiotensin-receptor blocker (ARB) would provide further clinical benefit. 2. The addition of candesartan to ACE inhibitor treatment led to significant reductions in cardiovascular mortality and hospitalization for heart failure when compared to placebo. 3. Patients taking candesartan experienced significantly higher rates of serum creatinine elevation and hyperkalemia. |
| The MIRACL trial: Atorvastatin reduces recurrent ischemia post-ACS | 2001 | JAMA | 1914 | 1. Atorvastatin 80 mg per day reduced the recurrence of ischemic events in the first 16 weeks after the onset of an ACS, defined as unstable angina or non-Q-wave MI 2. There was no statistically significant difference in the incidence of death, nonfatal MI, or cardiac arrest between the atorvastatin and placebo groups after an ACS |
| The iPrEx trial: Preexposure prophylaxis reduces HIV transmission in men and transgender women who have sex with men | 2010 | NEJM | 1907 | 1. In human immunodeficiency virus (HIV)-seronegative men and transgender women who have sex with men, preexposure prophylaxis with antiretrovirals significantly reduced the risk of HIV infection when compared with placebo. 2. There were similar rates of serious adverse events in both groups, though patients taking antiretroviral preexposure prophylaxis were significantly more likely to experience nausea and unintentional weight loss. |
| Interferon beta-1b for relapsing-remitting multiple sclerosis | 1993 | Neurology | 1901 | 1. Treatment with interferon beta-1b reduced the rate of multiple sclerosis exacerbations in patients with relapsing-remitting multiple sclerosis, in a dose-dependent fashion 2. Serial magnetic resonance imaging revealed less multiple sclerosis activity in patients with increasing doses of IFNB 3. There was no difference in disability caused by IFNB treatment |
| The PLCO trial 1: PSA and digital rectal examination in prostate cancer screening | 2009 | NEJM | 1821 | 1. Subjects undergoing annual prostate-specific antigen (PSA) testing for 6 years and annual digital rectal examination (DRE) for 4 years experienced significantly increased incidence of prostate cancer compared to usual care 2. Screening with PSA testing and DRE does not significantly reduce mortality from prostate cancer compared to usual care |
| The EMGT: Reducing intraocular pressure slows progression of glaucoma | 2002 | JAMA Opthalmology | 1805 | 1. Treatment using laser trabeculoplasty and topical betaxolol hydrochloride to reduce intraocular pressure (IOP) is associated with delayed progression of glaucoma. 2. Treatment to decrease IOP was associated with an increase in nuclear lens opacity grading indicative of cataract formation. |
| The COURAGE trial: PCI does not improve mortality in medically optimized patients with stable coronary artery disease | 2007 | NEJM | 1785 | 1.Addition of percutaneous cutaneous intervention (PCI) to optimal medical therapy for patients with stable coronary artery disease does not improve mortality or cardiovascular outcomes |
| The ECASS-III trial: Administering recombinant t-PA up to 4.5 hours after onset of acute ischemic stroke improves neurological outcomes | 2008 | NEJM | 1777 | 1.Alteplase administered between 3 to 4.5 hours after the onset of acute ischemic stroke improves functional outcomes at 90 days, when compared to placebo |
| The PLATO trial: Ticagrelor vs clopidogrel for ACS | 2009 | NEJM | 1771 | 1. Treatment with ticagrelor significantly reduces mortality in patients with acute coronary syndrome when compared to clopidogrel 2. Ticagrelor does not significantly increase the incidence of major bleeding |
| The AFFIRM trial: Rate-control vs. rhythm-control in atrial fibrillation | 2002 | NEJM | 1765 | 1.Rate-control, along with anticoagulation, should be the main approach to managing patients with atrial fibrillation 2.Compared to rhythm-control, rate-control resulted in a lower incidence of adverse events and no significant difference in mortality |
| The CHARM-Preserved trial: Candesartan in heart failure with preserved ejection fraction | 2003 | Lancet | 1708 | 1. In patients with heart failure and preserved ejection fraction, candesartan does not significantly reduce the rate of cardiovascular death, but does significantly reduce the rate of hospitalization for heart failure as compared with placebo |
| The MADIT-CRT trial: Cardiac resynchronization therapy in heart failure | 2009 | NEJM | 1676 | 1. In patients with heart failure, reduced left ventricular ejection fraction, and prolonged QRS>130 ms, treatment with cardiac resynchronization therapy (CRT), in addition to implantable cardioverter-defibrillator (ICD), significantly reduced the risk of heart failure events when compared with patients only receiving ICD. 2. The rates of device-related complications were similar between the two groups both in short- and long-term follow-up. |
| The ADVANCE trial: Intensive glycemic control reduces risk of nephropathy | 2008 | NEJM | 1637 | 1.Intensive glycemic control was significantly associated with lower rates of new or worsened nephropathy when compared to conventional glycemic control (≤ 180 mg/dL) 2.There was no significant reduction in major macrovascular events associated with intensive blood sugar control |
| Quadrivalent HPV vaccine in young women | 2005 | Lancet | 1602 | 1. Prophylactic use of a quadrivalent vaccine against HPV strains 6, 11, 16, and 18 significantly reduced the incidence of HPV infection and HPV-associated genital disease 30 months after vaccination 2. No significant adverse effects were observed to be due to the vaccinations |
| The CLARITY trial: Adding clopidogrel to STEMI management | 2005 | NEJM | 1598 | 1. The early addition of clopidogrel significantly reduced the incidence of infarct-related arterial re-occlusion within 30 days following myocardial infarction 2. Addition of early clopidogrel improved the outcomes of coronary angiography and decreased the need for early/emergent angiography during the event 3. There were no differences in major or minor bleeding or intracranial hemorrhage incidence between the clopidogrel group and the control group |
| Mild hypothermia improves neurological outcome after cardiac arrest | 2002 | NEJM | 1556 | 1. Initiation of hypothermia protocol for 24 hours after a cardiac arrest significantly improved neurological outcome in surviving patients 2. Patients who underwent the hypothermia protocol had a significantly lower mortality rate at 6 months 3. There were no significant differences in adverse outcomes between the two groups |
| The MDRD trial: Protein intake and blood pressure control in renal insufficiency | 1994 | NEJM | 1545 | 1. Reducing protein intake and lower blood pressure targets did not significantly delay the rate of decline in GFR in patients with renal insufficiency at 3 years 2. In patients with elevated baseline proteinuria (≥1 g/day in moderate insufficiency, ≥3 g/day in severe insufficiency), lower blood pressure targets significantly delayed the progression of renal disease |
| The SHIFT: Ivabradine in congestive heart failure | 1994 | Lancet | 1530 | 1. In patients with congestive heart failure (CHF) and baseline heart rate >70 bpm, ivabradine significantly reduced the risk of heart failure hospitalization and death from heart failure compared to placebo. 2. Compared to those on placebo, patients taking ivabradine experienced significantly higher rates of atrial fibrillation, asymptomatic and symptomatic bradycardia. |
| The Lee index: Risk of perioperative cardiac events | 1999 | Circulation | 1483 | 1.The Lee index is a prospectively validated model that predicts the risk of a cardiac event in patients undergoing noncardiac surgery 2.The six independent predictors are as follows: 1) high-risk surgery, 2) history of ischemic heart disease, 3) history of congestive heart failure, 4) history of cerebrovascular disease, 5) preoperative treatment with insulin, 6) preoperative serum creatinine >2.0 mg/dL (>177 µmol/L) |
| Early retroviral therapy reduces HIV-1 transmission | 2011 | NEJM | 1460 | 1. HIV-1 transmission rates were significantly lower in the early-therapy group compared to the delayed-therapy group 2. Patients in the early-therapy group had lower incidence of HIV-related clinical events with a lower viral load and higher CD4 cell count than those whose therapy was delayed |
| The CHOIR trial: Target lower hemoglobin levels in patients with anemia and chronic kidney disease | 2006 | NEJM | 1451 | 1.In patients with anemia and chronic kidney disease, treating with epoetin alfa to a lower hemoglobin target was associated with significantly reduced incidence of the composite event (death, MI, hospitalization for CHF, and stroke) 2.Achieving the lower hemoglobin target required significantly lower doses of epoetin alfa |
| The Term Breech trial: Cesarean delivery improves perinatal outcome | 2000 | Lancet | 1443 | 1. Among women with term fetuses in breech malpresentation, cesarean delivery was associated with reduction in perinatal and neonatal mortality and morbidity. |
| Dose-response relationship noted between television watching and obesity | 1985 | Pediatrics | 1414 | 1. A dose-response relationship was observed between child and adolescent television watching and obesity in children studied through the National Health Examination Survey 2. In multiple regression analysis, only prior history of obesity was found to be more influential than television watching on obesity prevalence |
| The DIGAMI trial: Insulin-glucose infusion in diabetics with acute MI | 1995 | JACC | 1413 | 1. In diabetic patients with acute myocardial infarction, insulin-glucose infusion with subsequent long-term insulin treatment reduces mortality at 1 year |
| The ARDSNet trial: Lower tidal volume ventilation in ALI/ARDS | 2000 | NEJM | 1410 | 1. The trial was terminated early when the data demonstrated that lower tidal volume ventilator settings in ALI/ARDS patients led to a significant decrease in in-hospital mortality 2. Low tidal volume ventilation also led to an increase in ventilator-free days and a decrease in the number of days with systemic organ failure. There was no change in the incidence of barotrauma between the two groups 3. Patients assigned to lower tidal volume ventilator settings initially required a higher PEEP to maintain arterial oxygenation and were more likely to develop respiratory acidosis, although the difference disappeared by day 7 |
| The COMMIT trial: Metoprolol and clopidogrel in patients with acute MI | 2005 | Lancet | 1400+ | 1. Adding early metoprolol does not further decrease the risk of death post-MI compared to conventional fibrinolytic therapy alone 2. Use of early metoprolol decreases the risk of reinfarction and ventricular fibrillation, but increases the risk of cardiogenic shock 3. Adding clopidogrel to aspirin decreases the combined risk of death, reinfarction, or stroke post-MI, without significantly increasing the risk of major bleeding |
| The NETT: Lung-volume-reduction surgery in emphysema | 2003 | NEJM | 1386 | 1. Lung-volume-reduction surgery significantly improves exercise capacity, but not overall survival, in patients with emphysema when compared with medical therapy 2. Post hoc subgroup analyses showed that in patients with upper-lobe emphysema and low baseline exercise capacity, lung-volume-reduction surgery significantly decreased mortality compared to medical therapy |
| Vena caval filters in pulmonary embolism prophylaxis | 1998 | NEJM | 1365 | 1. Permanent vena caval filter placement in addition to anticoagulant therapy helps prevent short-term occurrence of pulmonary embolism but increases the risk of recurrent DVT in the long-term 2. There is no significant difference in efficacy between LMWH and UFH during early anticoagulant therapy for PE prophylaxis |
| Vena caval filters in pulmonary embolism prophylaxis | 1998 | NEJM | 1356 | 1. Permanent vena caval filter placement in addition to anticoagulant therapy helps prevent short-term occurrence of pulmonary embolism but increases the risk of recurrent DVT in the long-term 2. There is no significant difference in efficacy between LMWH and UFH during early anticoagulant therapy for PE prophylaxis |
| Cervical length indicates risk of preterm delivery | 1996 | NEJM | 1337 | 1. Transvaginal cervical length measured at 24 and 28 weeks gestation was inversely associated with risk of spontaneous preterm delivery in a dose-dependent manner. |
| The SYNTAX trial: CABG superior to PCI in triple-vessel or left main artery disease | 2009 | NEJM | 1293 | 1.In severe coronary artery disease, CABG is superior to PCI in reducing the need for repeat vascularization 2.CABG should remain the standard of care for severe coronary artery disease, despite being associated with a higher risk of stroke |
| The SOLVD trial: Enalapril in heart failure with reduced ejection fraction | 1991 | NEJM | 1286 | 1. Enalapril significantly reduced the risk of all-cause mortality in patients with congestive heart failure and reduced left ventricular ejection fraction (LVEF≤35%) compared to placebo 2. Patients being treated with enalapril had significantly higher risk of developing elevated serum potassium levels and serum creatinine levels |
| PROS network study examines pubertal onset by race/ethnic groups | 1997 | Pediatrics | 1248 | 1. In a study population of girls 3-12 years of age, it was found that African-American females developed secondary sexual characteristics at a significantly earlier age than white girls 2. African-American females had earlier menarche at 12.16 years of age, compared to 12.88 years of age among white females |
| Donepezil and vitamin E in Alzheimer’s disease | 2005 | NEJM | 1242 | 1. High-dose vitamin E supplementation does not slow down progression to Alzheimer’s disease 2. Donepezil, a cholinesterase inhibitor, shows modest reductions in risk of progression to Alzheimer’s disease early in treatment |
| High fertilization rates following intracytoplasmic sperm injection (ICSI) | 1993 | Obstetrics & Gynecology | 1226 | 1. Among infertile couples with poor prognosis and/or severe male factor infertility, intracytoplasmic sperm injection (ICSI) was associated with higher fertilization, implantation, and pregnancy rates. |
| The ARISTOTLE trial: Apixaban vs warfarin in atrial fibrillation | 2011 | NEJM | 1225 | 1. Apixiban is superior to warfarin in preventing stroke in patients with atrial fibrillation 2. Apixaban has a decreased risk of intracranial hemorrhage compared to warfarin 3. There is no difference in GI bleeding risk between apixaban and warfarin |
| The NICE-SUGAR trial: Intensive glycemic control harmful in the ICU | 2009 | NEJM | 1216 | 1.Tight glycemic control (81-108 mg/dL) in critically ill patients is associated with higher mortality when compared to conventional glycemic control (≤ 180 mg/dL) |
| The ACCOMPLISH trial: ACE inhibitors and calcium channel blockers for hypertension | 2008 | NEJM | 1205 | 1. Benazepril plus amlodipine offers the same effect at reducing blood pressure in hypertensive patients as benazepril plus hydrochlorothiazide 2. Benazepril plus amlodipine was more effective than benazepril plus hydrochlorothiazide at reducing cardiovascular events in hypertensive patients at risk for such events |
| Adverse pregnancy outcomes associated with thrombophilias | 1999 | NEJM | 1196 | 1. The incidence of genetic thrombophilias was found to be higher in women with adverse pregnancy outcomes. |
| The ONTARGET trial: Telmisartan is non-inferior to ramipril in improving cardiovascular outcomes in high-risk populations | 2008 | NEJM | 1172 | 1.The angiotensin receptor blocker (ARB) telmisartan is non-inferior to the ACE-inhibitor rampiril in improving cardiovascular outcomes in high-risk populations 2.Telmisartan is significantly less often associated with angioedema and cough compared to ramipril 3.Telmisartan in addition to ramipril in high risk populations does not offer additional benefit, and is associated with increased risk of complications |
| Association of bacterial vaginosis and low birthweight infants | 1995 | NEJM | 1169 | 1. Bacterial vaginosis (BV) is associated with 40% increased odds of preterm delivery of a low birthweight (LBW) infant. |
| Albumin in cirrhotic patients with spontaneous bacterial peritonitis | 1999 | NEJM | 1129 | 1. In cirrhotic patients with spontaneous bacterial peritonitis, albumin infusion on days 1 and 3 of treatment in addition to antibiotics significantly reduces the risk of developing renal impairment and mortality when compared with antibiotics alone |
| The PARADIGM-HF trial: Valsartan-neprilysin inhibitor vs. enalapril in patients with heart failure | 2014 | NEJM | 1127 | 1. LCZ696, a combination of valsartan with a neprilysin inhibitor, significantly reduced the risk of death from cardiovascular causes and hospitalization due to heart failure when compared to enalapril. 2. There were no significant differences between the two groups in the risk of angioedema, though patients treated with LCZ696 experienced significantly higher rates of symptomatic hypotension. |
| The UPLIFT trial: Tiotropium in chronic obstructive pulmonary disease | 2008 | NEJM | 1104 | 1. Tiotropium does not significantly reduce the mean rate of decline in FEV1, a common metric of COPD progression 2. Tiotropium significantly improves patients’ quality of life, mean FEV1, and decreases the incidence of disease exacerbation |
| The SPRINT: Intensive vs. standard blood pressure control | 2015 | NEJM | 1073 | 1. In patients with hypertension and elevated cardiovascular risk, treating to a target systolic blood pressure of 120 mmHg significantly reduced the risk of heart failure and cardiovascular mortality when compared with the standard target of 140 mmHg. 2. Patients in the intensive group experienced significantly higher rates of hypotension, syncope, electrolyte abnormalities, and acute kidney injury compared to those in the standard group. |
| The SAFE trial: Normal saline vs. albumin for fluid resuscitation | 2004 | NEJM | 1071 | 1.There was no significant difference in 28-day mortality when comparing albumin and normal saline for fluid resuscitation in the intensive care setting 2.Compared to normal saline, fluid resuscitation with albumin did not yield any significant benefits in terms of secondary outcomes (i.e., length of ICU/hospital stay, duration of supportive treatment measures) |
| The ENHANCE trial: Simvastatin and ezetimibe in familial hypercholesterolemia | 2008 | NEJM | 1064 | 1. In patients with familial hypercholesterolemia, simvastatin and ezetimibe combination therapy does not result in significant differences in carotid artery thickness when compared to treatment with simvastatin alone 2. Treatment with simvastatin and ezetimibe led to significant greater reductions in LDL cholesterol, triglyceride, and C-reactive protein levels as compared to treatment with simvastatin alone 3. There were no significant differences between the two groups in the rates of adverse events or drug discontinuation |
| The CORTICUS trial: Hydrocortisone in septic shock | 2008 | NEJM | 1051 | 1. There was no significant difference in mortality between patients with septic shock receiving low-dose hydrocortisone compared to placebo 2. Hydrocortisone therapy reversed shock more quickly, but resulted in more cases of superinfection |
| Anastrazole superior to tamoxifen for breast cancer treatment | 2000 | Journal of Clinical Oncology | 1018 | 1. Postmenopausal women with advanced breast cancer randomized to anastrazole as first-line therapy experienced an increase in time to progression and a more favorable side effect profile compared to women randomized to tamoxifen treatment. |
| The ONTT: Intravenous steroids lead to faster visual recovery in optic neuritis | 1992 | NEJM | 1012 | 1. In patients with first presentation of optic neuritis, treatment with intravenous methylprednisolone followed by oral prednisone resulted in faster visual recovery when compared to placebo, though only a small benefit persisted by 6 months. 2. The use of oral prednisone alone demonstrated no benefit in terms of visual recovery and appeared to increase the risk of recurrent episodes of optic neuritis compared to placebo. |
| The CURB-65 score: Risk stratifying patients with community-acquired pneumonia | 2003 | Thorax | 1009 | 1.Patients with community acquired pneumonia (CAP) can be stratified into mortality risk groups using a six-point score (one point for each category present on initial presentation): Confusion, Urea >7 mmol/L, Respiratory rate >30/min, low systolic (<90 mm Hg) or diastolic (<60 mm Hg) Blood pressure, age >65 years (CURB-65) 2.Patients who receive a score of >2 are at a high risk of mortality (>19%) and should be treated in hospital or considered for ICU admission |
| The FREEDOM trial: Coronary bypass graft vs. PCI in diabetic patients | 2012 | NEJM | 992 | 1. In patients with diabetes and multivessel disease, coronary artery bypass grafting (CABG) was shown to be superior to percutaneous coronary intervention (PCI) with drug-eluting stents in reducing the risk of all-cause mortality and nonfatal myocardial infarction. 2. Patients treated with PCI experienced a smaller risk of nonfatal stroke, but also had significantly higher rates of revascularization within a year of their procedure compared to those treated with CABG. |
| The SPAF trial: Warfarin and aspirin reduce the risk of stroke in atrial fibrillation | 1991 | Circulation | 989 | 1. Patients with atrial fibrillation are at higher risk of ischemic stroke and systemic embolism. 2. Compared to placebo, warfarin and aspirin significantly reduced the risk of ischemic stroke and systemic embolism in patients with atrial fibrillation. 3. Today, antithrombotic therapy remains a vital consideration in managing patients with atrial fibrillation, though many more agents are available. |
| IVIg with aspirin linked to reduced coronary aneurysms | 1986 | NEJM | 984 | 1. Children with Kawasaki disease treated with a combined regimen of aspirin and intravenous gamma globulin had significantly lower rates of coronary artery aneurysms when compared to those receiving aspirin only 2. Children treated with the combined regimen had significantly shorter fevers and a greater decrease in inflammatory markers when compared to those treated with aspirin alone |
| The SPARCL trial: Atorvastatin reduces risk of stroke and cardiovascular events in patients with recent stroke or transient ischemic attack | 2006 | NEJM | 972 | 1.In patients with recent stroke or TIA, high-dose atorvastatin significantly reduces the risk of fatal stroke compared to placebo 2.Atorvastatin was also associated with a significant reduction in risk of cardiovascular events |
| The CLOT trial: Dalteparin better than warfarin in preventing recurrent venous thromboembolism in patients with malignancy | 2003 | NEJM | 950 | 1.Dalteparin, a low-molecular-weight heparin, is superior to warfarin in preventing recurrent venous thromboembolism in the setting of malignancy 2.There was no significant difference in risk of major bleeding with dalteparin as compared to warfarin |
| The ATLAS trial: ACE inhibitor dosing in chronic heart failure | 1999 | Circulation | 949 | 1. When compared to a lower dose, high-dose angiotensin-converting-enzyme inhibitor significantly reduced the risk of hospitalization or death in patients with chronic heart failure |
| Progesterone injections reduce recurrent preterm birth | 2003 | NEJM | 946 | 1. In women with a history of preterm birth, weekly progesterone injections reduced the risk of delivery prior to 37, 35, and 32 weeks gestation. 2. Number needed to treat to prevent one preterm birth <37 weeks was six women. |
| The CHARM-Alternative trial: Angiotensin-receptor blockers in heart failure | 2003 | Lancet | 928 | 1. Candesartan reduced cardiovascular death and hospital admission for chronic heart failure in patients with heart failure and reduced ventricular function intolerant to ACE inhibitors 2. Candesartan was well-tolerated in patients with previous intolerance to ACE inhibitors |
| Sleep-disordered breathing associated with poor academics and surgical improvement | 1998 | Pediatrics | 911 | 1. Sleep-associated gas exchange abnormalities were highly prevalent among a first-grade study cohort with poor academic performance. About 18% of participants had oxygenation abnormalities assessed during overnight observation 2. School performance, as gauged by grades, improved significantly among children who received surgical intervention for abnormal breathing patterns during sleep 3. Symptoms of disordered sleep, as assessed by follow-up questionnaire, were significantly worse among children who did not undergo surgical tonsillectomy and adenoidectomy |
| The WARSS trial: Warfarin vs. aspirin in preventing recurrent ischemic stroke | 2001 | NEJM | 908 | 1. Warfarin is not superior to aspirin in preventing recurrent ischemic stroke in patients with a prior noncardioembolic ischemic stroke 2. There was no significant difference in the rates of major hemorrhage when comparing warfarin with aspirin |
| The CNTG trial: Intra-ocular pressure reduction slows progression of normal-tension glaucoma | 1998 | American Journal of Opthalmology | 892 | 1. Reduction of intra-ocular pressure (IOP) with topical medications in normal-tension glaucoma significantly reduced risk of progression to visual field impairment and/or optic disc damage. |
| The CAPRICORN trial: Beta-blockers in acute myocardial infarction | 2001 | Lancet | 869 | 1. Carvedilol significantly reduced mortality from cardiovascular causes and recurrent non-fatal MI 2. While carvedilol treatment was associated with a 23% relative risk reduction in all-cause mortality, this did not reach statistical significance 3. These findings are consistent with previous trials exploring the benefits of beta-blockers in managing acute MI |
| The CREST trial: Stenting versus endarterectomy for carotid stenosis | 2010 | NEJM | 865 | 1. The rate of stroke, myocardial infarction or death did not differ significantly between patients treated with carotid artery stenting compared to carotid endarterectomy 2. The periprocedural rate of stroke was higher with stenting while the rate of myocardial infarction was higher with endarterectomy |
| The DOSE trial: Loop diuretic strategies in acute decompensated heart failure | 2011 | NEJM | 830 | 1. The use of loop diuretics in acute decompensated heart failure is commonplace, but clinical practice varies widely with regards to the dosage and administration of therapy. 2. This study found that mode of administration (bolus vs. continuous infusion) and dosage (low vs. high) of loop diuretics had no significant effect on the primary endpoints of overall effectiveness or safety of therapy. 3. Higher doses of loop diuretics led to significantly greater diuresis, improved dyspnea, and fewer adverse events than lower doses. |
| The ROCKET AF: Rivaroxaban in atrial fibrillation | 2011 | NEJM | 824 | 1.Rivaroxaban is non-inferior to warfarin in preventing strokes and systemic embolism 2.Although there is no significant difference between the two in the incidence of clinically relevant bleeding, rivaroxaban is associated with significantly lower rates of critical, fatal, and intracranial bleeding |
| Aspirin vs warfarin in atherosclerotic intracranial stenosis | 2005 | NEJM | 813 | 1. There was no difference between warfarin and aspirin in preventing recurrent stroke in patients with significant atherosclerotic intracranial stenosis. 2. Warfarin was associated with a significantly higher incidence of major hemorrhage compared to the aspirin group. |
| The NINDS trial: Tissue plasminogen activator in acute ischemic stroke significantly improves functional outcomes | 1995 | NEJM | 808 | 1.Treatment of acute ischemic stroke with tissue plasminogen activator within 3 hours of symptom onset significantly improves functional outcomes three months after the incident, when compared with placebo 2.Tissue plasminogen activator is significantly associated with higher rates of symptomatic intracerebral hemorrhage |
| Doppler velocimetry of fetal middle cerebral artery predicts anemia | 2000 | NEJM | 797 | 1. Among fetuses at risk for maternal red cell alloimmunization, peak systolic velocity in the middle cerebral artery is a sensitive predictor of moderate or severe fetal anemia. |
| Low maternal serum AFP associated with fetal aneuploidy | 1984 | AJOG | 792 | 1. Compared to matched controls, women with infants affected by aneuploidy were more likely to have low levels of maternal serum a-fetoprotein. |
| Computerized order system linked with increased pediatric mortality | 2005 | Pediatrics | 789 | 1. The use of a computerized physician order entry (CPOE) program in a large, tertiary pediatric hospital was associated with over 3 times increased risk of mortality when compared to patients admitted to the same center prior to CPOE implementation 2. CPOE implementation resulted in increased physician time placing medication orders as opposed to providing patient care and delays in medication administration as medications now were located in the hospital pharmacy, not at the bedside |
| The Rockall score: Risk assessment after acute upper gastrointestinal haemorrhage | 1996 | Gut | 775 | 1. Age, shock, comorbidity, diagnosis, major stigmata of recent haemorrhage, and rebleeding were found to be independent predictors of mortality following acute upper gastrointestinal haemorrhage |
| The CARP trial: Preoperative revascularization prior to elective vascular surgery | 2004 | NEJM | 771 | 1. In patients with stable coronary artery disease undergoing elective vascular surgery, preoperative revascularization does not significantly reduce short- or long-term mortality 2. Patients undergoing revascularization experience significant time delays prior to surgery |
| Parents define children’s oncology-related palliation and pain relief | 2000 | NEJM | 766 | 1. When interviews with parents who lost children to cancer were compared to patient hospital records, researchers found that many children experienced substantial suffering toward the end of life with poorly managed symptoms 2. There was significant discordance between parent and physician reports of patient discomfort, with parents being significantly more likely to report patient symptoms than physicians |
| Antibiotic GBS prophylaxis linked to decreased early-onset neonatal infection | 2000 | NEJM | 758 | 1. During the 1990-1998 study period, which included the 1996 initiation of national Group B Streptococcus guidelines, a significant, 65% decrease in early-onset neonatal disease was observed 2. During the study’s final year, an estimated 3900 early-onset neonatal GBS cases along with 200 early- and late-onset neonatal deaths were believed to have been prevented through the use of recommended antibiotic prophylaxis |
| Glyburide as effective as insulin for gestational diabetes | 2000 | NEJM | 755 | 1. Among women with gestational diabetes requiring treatment, those randomized to glyburide achieved similar glycemic control to women in the insulin control group. |
| Prophylactic penicillin and reduced septicemia in sickle cell patients | 1986 | NEJM | 751 | 1. This randomized, placebo-controlled, double-blinded trial demonstrated an 84% reduction in the incidence of pneumococcal septicemia among patients with sickle cell taking prophylactic penicillin when compared to those taking placebo 2. Fifteen severe, Streptococcus pneumoniae-related infections occurred during the study with 13 occurring in patients taking placebo, 3 of which resulted in death. No patients taking prophylactic penicillin died during the study course |
| Artificial surfactant linked to significant improvement of RDS | 1980 | Lancet | 748 | 1. Among 10 infants treated for respiratory distress syndrome with artificial surfactant in this landmark trial, significant improvements in blood pressure, acid-base status, arterial oxygenation, and radiologic findings were observed 2. Infants also required significantly less oxygen therapy and ventilator pressure following surfactant administration |
| The EMPHASIS-HF trial: Eplerenone in mild systolic heart failure | 2011 | NEJM | 736 | 1. Eplerenone significantly reduces mortality in patients suffering from heart failure with reduced systolic function (LVEF≤30%, or 30-35% if QRS>130 ms) and mild symptoms (NYHA class II) when compared with placebo 2. The incidence of hyperkalemia was significantly higher in the eplerenone group |
| The POISE trial: Perioperative use of beta-blockers | 2008 | Lancet | 722 | 1.The POISE trial was a randomized controlled trial exploring the effect of perioperative beta-blockers on cardiac death, nonfatal MIs, and nonfatal cardiac arrest 2.Perioperative oral extended-release metoprolol was found to reduce the risk of nonfatal MI, while increasing the risk of stroke and mortality when compared to placebo |
| Tenofovir-emtricitabine more effective and safer than zidovudine-lamivudine in HIV treatment | 2006 | NEJM | 714 | 1. A significantly higher percentage of patients taking tenofovir, emtricitabine, and efavirenz had HIV viral load <50 copies/mL than those taking zidovudine, lamivudine, and efavirenz 2. Significantly more patients discontinued medication in the zidovudine-lamivudine group due to adverse events than in the tenofovir-emtricitabine group |
| The ESPRIT trial: Aspirin with dipyridamole after cerebral ischemia | 2006 | Lancet | 686 | 1. The combination of aspirin and dipyridamole was superior to aspirin alone in the secondary prevention of major vascular events 2. Patients on combination therapy were more likely to discontinue trial medication due to adverse effects |
| Adjuvant dexamethasone improves outcomes in adult bacterial meningitis | 2002 | NEJM | 683 | 1.Treatment with dexamethasone reduces morbidity and mortality in adults with bacterial meningitis 2.There is no significant difference in risk of adverse events with corticosteroid treatment |
| The ABCD2 score: Risk of stroke after TIA | 2007 | Lancet | 674 | 1. The ABCD2 score is a validated, seven-point, risk-stratification tool to identify patients at high risk of stroke following a TIA Patients with scores ≥4 are at considerably higher risk of stroke in the 2-day period following a TIA, and may potentially require urgent intervention |
| The TRANSFORMS trial: Fingolimod vs interferon in multiple sclerosis | 2010 | NEJM | 662 | 1. Fingolimod significantly reduced the number of relapses as compared to interferon beta-1a over a one-year period 2. Fingolimod was associated with more transient bradycardia and a higher infection rate as compared to interferon |
| The ORACLE trial: Antibiotics for preterm, prelabor rupture of membranes | 2001 | Lancet | 660 | 1. Among infants born to women with preterm, premature rupture of membranes, those whose mothers were randomized to treatment with erythromycin experienced a lower incidence of adverse neonatal outcomes and prolongation of pregnancy compared to the placebo group. |
| Risks associated with a Trial of Labor after Cesarean Delivery (TOLAC) | 2004 | NEJM | 655 | 1. Uterine rupture occurs in less than 1% of women undergoing TOLAC 2. The absolute risk of permanent neurological impairment in infants born to women undergoing TOLAC is <1% (0.46 per 1000 women) |
| The NLST trial: CT screening reduces lung cancer mortality | 2011 | NEJM | 647 | 1. Low-dose computed tomography screening reduces lung cancer mortality when compared to screening with chest radiography 2. Screening for lung cancer with either modality resulted in very high false positive rates |
| The Wells DVT criteria: Clinical prediction model for deep vein thrombosis | 2003 | NEJM | 643 | 1.The Wells DVT criteria are a validated clinical model for estimating pre-test probability of DVT 2.D-dimer testing in outpatients can help inform the need for venous ultrasonography in the diagnosis of DVT |
| The HAS-BLED score: Bleeding risk in atrial fibrillation | 2010 | Chest | 638 | 1. The HAS-BLED score is an easy to remember and easy to apply tool that has good predictive accuracy for the risk of major bleeding in patients with atrial fibrillation 2. Since its publication, the HAS-BLED score has been validated in a large cohort study of 7,329 patients |
| Behavioral intervention superior for urge incontinence | 1998 | JAMA | 600 | 1. For treatment of urgency incontinence, behavioral intervention was associated with the greatest reduction in incontinence episodes and the highest patient satisfaction rates compared to standard drug treatment with oxybutynin or placebo. |
| Low-lead exposure in childhood associated with worse cognitive performance | 1992 | Pediatrics | 588 | 1. Among children exposed to lead early in life, serum lead levels at 24 months of age were significantly associated with decreased cognitive performance on measures of intelligence and educational achievement at 10 years old 2. Each 0.48 μmol/L (10 μg/dL) increase in serum lead at 24 months of age was associated with a 5.8 point decline in a measure of intelligence quotient and an 8.9 point decline in educational achievement score during cognitive testing at 10 years of age |
| Intravenous omeprazole after endoscopy reduces rebleeding in patients with peptic ulcers | 2000 | NEJM | 583 | 1.After endoscopic treatment, intravenous omeprazole significantly reduces the risk of rebleeding in patients with peptic ulcers at 3, 7, and 30 days |
| Childhood febrile seizure characteristics associated with epilepsy diagnosis | 1976 | NEJM | 580 | 1. Through the inclusion of infants from the Collaborative Perinatal Project, this large, multicenter, prospective study found that children with febrile seizures, complex febrile seizures (seizures that were longer than 15 minutes in duration, occurred more than once in 24 hours, or had focal neurologic findings), and febrile seizures of earlier onset (before 6 months of age) were at increased risk of developing epilepsy when compared to individuals who had febrile seizures without these features 2. Abnormal performance on neurologic testing was linked to increased epilepsy risk |
| The STAR*D trials II: Switching antidepressants | 2006 | NEJM | 567 | 1.In cases where citalopram fails or cannot be tolerated, approximately 1 in 4 patients will experience remission of their depression symptoms by switching to sustained-release buproprion, sertraline, or extended-release venlafaxine |
| The ACURASYS trial: Neuromuscular blockade in early ARDS | 2010 | NEJM | 566 | 1. In patients with severe acute respiratory distress syndrome (ARDS), treatment with neuromuscular blockade in the first 48 hours significantly reduced 90-day and 28-day mortality when compared to placebo. 2. The group treated with the neuromuscular blocker also experienced significantly lower rates of barotrauma and there were no differences between the groups in terms of ICU-acquired paresis. |
| Early initiation of antiretroviral therapy significantly improves HIV survival | 2009 | NEJM | 564 | 1.The relative risk of death was significantly higher in patients who deferred antiretroviral therapy compared to those who initiated treatment early on 2.This finding remained significant after adjustment for independent risk factors of age, history of injection drug use and HCV infection |
| Hepatocellular carcinoma screening reduces mortality | 2004 | Journal of Cancer Research and Clinical Oncology | 559 | 1. Patients at high risk for hepatocellular carcinoma who underwent biannual screening with serum AFP levels and liver ultrasound were much more likely to be diagnosed with cancer in the earlier stages and receive curative treatment 2. Biannual screening for hepatocellular carcinoma leads to a significant reduction in 5-year mortality |
| The COPERNICUS trial: Carvedilol in severe chronic heart failure | 2002 | Circulation | 557 | 1. Adding carvedilol to the management of patients with severe heart failure (NYHA Class III-IV and LVEF<25%) is associated with a 35% relative risk reduction in mortality 2. In this patient population, carvedilol is also associated with decreased risk of hospitalization and serious adverse effects, as well as improvement in symptoms |
| MMR vaccine not associated with autism | 2002 | NEJM | 550 | 1. Among children born in Denmark during a 7-year study period, no increase in risk of developing autism was seen in those who were vaccinated against measles, mumps, and rubella relative to unvaccinated children |
| The RE-COVER trial: Dabigatran is non-inferior to warfarin in treating acute venous thromboembolism | 2009 | NEJM | 549 | 1.The RE-COVER trial demonstrates that treating acute venous thromboembolism with 6 months of dabigatran 150 mg twice daily is non-inferior to dose-adjusted warfarin to an INR of 2-3 2.Though dabigatran therapy does not require INR monitoring, it is considerably more expensive than warfarin |
| The STAR*D trials I: Medication augmentation for depression | 2006 | NEJM | 541 | 1.In patients who have not experienced remission of depression despite vigorous treatment with an SSRI, augmentation of treatment by adding buproprion or buspirone can achieve remission in approximately 30% of patients 2.There were no significant differences between the two groups in terms of remission rates |
| The Canadian CT Head Rule: A highly sensitive clinical decision rule for patients with minor head injuries | 2001 | Lancet | 524 | 1.The Canadian CT Head Rule consists of 7 predictor variables to assess the need for CT imaging in patients with minor head injuries 2.This study demonstrates that the rule is highly sensitive and may help to reduce the number of CT scans ordered |
| The Magpie trial: Magnesium lowers eclampsia risk | 2002 | Lancet | 518 | 1. Women with pre-eclampsia randomized to magnesium experienced a greater than 50% reduction in eclampsia compared to women on placebo. |
| The NASCET: Carotid endarterectomy for symptomatic stenosis | 1991 | NEJM | 516 | 1. Carotid endarterectomy, in addition to medical therapy, significantly reduces risk of major and fatal stroke in patients with symptomatic, high-grade (70-99%) carotid stenosis |
| The CARESS trial: Dual antiplatelet therapy superior to monotherapy in symptomatic carotid stenosis | 2005 | Circulation | 485 | 1. Dual antiplatelet therapy with clopidogrel and aspirin was associated with a significant reduction in microembolic events in patients with symptomatic carotid stenosis compared to aspirin alone 2. There was no significant difference between the two groups in the risk of bleeding |
| The Symplicity HTN-2 trial: Renal denervation in treatment-resistant hypertension | 2010 | Lancet | 484 | 1. Renal denervation significantly reduces blood pressure in patients suffering from treatment-resistant hypertension 2. Renal denervation was not associated with a significantly higher rate adverse events in comparison to control |
| Laboratory values and treatment associated with DKA-related cerebral edema | 2001 | NEJM | 478 | 1. Among children admitted to 1 of 10 medical centers for diabetic ketoacidosis management, elevated serum urea nitrogen concentrations and low partial pressures of carbon dioxide were associated with significant increases in risk of developing cerebral edema 2. Lack of pronounced serum sodium rise and use of bicarbonate for treatment were also associated with significantly increased cerebral edema risk |
| Endoscopic biliary drainage in acute cholangitis | 1992 | NEJM | 471 | 1. For patients with severe acute cholangitis due to choledocholithiasis, endoscopic biliary drainage reduces hospital mortality compared to surgical decompression 2. Endoscopic biliary drainage is associated with fewer post-treatment complications compared to surgical decompression, although the decrease was not statistically significant for all types of complications |
| Magnesium sulfate in torsade de pointes | 1988 | Circulation | 466 | 1. Intravenous magnesium sulfate was effective at acutely terminating torsade de pointes 2. intravenous magnesium sulfate was not effective in terminating other ventricular tachycardias not associated with QT prolongation |
| Vancomycin superior to metronidazole for severe C. difficile-associated diarrhea | 2007 | CID | 459 | 1. Metronidazole and vancomycin had similar efficacy in treating mild cases of Clostridium difficile-associated diarrhea (CDAD) 2. Vancomycin was superior to metronidazole in treating severe cases of CDAD |
| Fidaxomicin vs. vancomycin in C. difficile infection | 2011 | NEJM | 452 | 1. Fidaxomicin is non-inferior to vancomycin in achieving clinical cure of C. difficile infection 2. Fidaxomicin therapy significantly reduces the rate of recurrence and significantly increases the rate of global cure of C. difficile infection when compared with vancomycin therapy |
| The WOEST trial: Double vs. triple therapy in patients requiring PCI and anticoagulation | 2013 | Lancet | 449 | 1. In patients requiring percutaneous coronary intervention (PCI) and long-term oral anticoagulation, treating with clopidogrel alone (i.e., double therapy) significantly reduced the risk of bleeding when compared to a combination of aspirin and clopidogrel (i.e., triple therapy). 2. There were no differences between the two groups in the risk of myocardial infarction, stroke, target vessel revascularization, or stent thrombosis. |
| The RAVE trial: Rituximab for ANCA-associated vasculitis | 2010 | NEJM | 442 | 1. Rituximab is non-inferior to cyclophosphamide in inducing remission of severe ANCA-associated vasculitis 2. There were no significant differences between the two groups in the rate of total, serious, or non-disease-related adverse events |
| Prone sleeping position and heavy bedding associated with SIDS | 1990 | BMJ | 432 | 1. In a study of sudden death in infants compared to matched controls, a significant increase in risk of death from unknown causes also called sudden infant death syndrome (SIDS) was observed among infants who slept prone as opposed to sleeping on their side or supine 2. A significant increase in SIDS risk was seen among infants who were wrapped in more blankets, wore heavier clothing to bed, or were in a home that was heated overnight when compared to control infants |
| Fecal transplantation in recurrent C. difficile infection | 2013 | NEJM | 428 | 1. Treating recurrent C. difficile infection with infusion of donor feces resulted in significantly higher cure rates than treating with vancomycin-alone or vancomycin with bowel lavage 2. Adverse events immediately after feces infusion included diarrhea, cramping, and belching |
| The DIG trial: Digoxin associated with significant decrease in hospitalizations in patients with systolic heart failure | 1997 | NEJM | 425 | 1.Digoxin significantly reduced hospitalizations but had no significant effect on mortality when used to treat patients with systolic heart failure 2.Digoxin was most beneficial in patients with low ejection fractions (<0.25) and poor functional status (nyha iii-iv) |
| The ACTIVE trial: Dual antiplatelet therapy in atrial fibrillation | 2009 | NEJM | 415 | 1.In patients with atrial fibrillation who require anticoagulation but cannot tolerate warfarin, dual anti-platelet therapy may be a potential alternative 2.Clopidogrel 75 mg PO daily, in addition to daily aspirin, significantly reduced the incidence of stroke and increased the incidence of major bleeding in patients with atrial fibrillation when compared to treatment with aspirin alone |
| The RIVAL trial: Radial vs femoral artery access for PCI | 2011 | Lancet | 414 | 1. The composite outcome of death, myocardial infarction, stroke, and non-CABG-related major bleeding did not differ between radial and femoral access for percutaneous coronary intervention 2. Radial artery access is associated with a significantly lower rate of vascular complications compared to femoral access |
| The COGENT trial: Omeprazole with dual anti-platelet therapy reduces upper gastrointestinal bleeding | 2010 | NEJM | 390 | 1.Concomitant administration of omeprazole decreases upper gastrointestinal bleeding in patients with coronary artery disease receiving dual anti-platelet therapy (i.e., aspirin and clopidogrel) 2.There is no significant increase in the risk of cardiovascular events with concomitant use of clopidogrel and omeprazole, a concern raised by previous observational studies |
| CT scans associated with increased risk of malignancy | 2012 | Lancet | 381 | 1. Through a retrospective cohort analysis of children and young adults without previous malignancy, patients exposed to multiple CT scans were found to be at over 3 times increase risk of developing leukemia and brain tumors |
| The RE-ALIGN trial: Dabigatran vs. warfarin for mechanical heart valves | 2013 | NEJM | 375 | 1. In patients with mechanical heart valves, anticoagulation with dabigatran was associated with significantly higher rates of stroke and major bleeding when compared to warfarin. 2. Based on these findings, patients with mechanical heart valves should be anticoagulated with warfarin, as opposed to dabigatran. |
| Diffusion-weighted MRI highly sensitive, specific vs. CT in acute ischemic stroke | 2002 | Stroke | 363 | 1. Among patients with acute neurologic deficits presenting within six hours of symptoms onset, diffusion-weight magnetic resonance imaging (DWI) was shown to be significantly more sensitive and specific for the diagnosis of ischemic stroke than non-contrast computed tomography (NCCT). |
| The ICTUS trial: Early invasive or selectively invasive management for ACS | 2005 | NEJM | 352 | 1. There was no significant difference in the composite rate of death, nonfatal myocardial infarction, or rehospitalization for angina in patients with acute coronary syndromes treated with early invasive versus selectively invasive strategies 2. Myocardial infarction was significantly more frequent in the early invasive management group but rehospitalization was significantly less frequent in this group |
| Early infant CF diagnosis associated with improved nutritional status | 2001 | Pediatrics | 327 | 1. Among infants randomized to undergo either newborn screen with cystic fibrosis (CF) testing included or undergo normal pediatric surveillance, those who underwent newborn screen were diagnosed significantly earlier 2. Infants diagnosed based on surveillance were significantly more likely to be severely malnourished compared to those diagnosed by newborn screen |
| Worse side effects following transobturator sling | 2010 | NEJM | 324 | 1. Retropubic tension free vaginal tape (TVT) and transobturator tape (TOT) were associated with similar success rates for treatment of stress urinary incontinence at one year. 2. TOT was associated with worrisome side effects like obturator neuropathies, while TVT was associated with more readily preventable and treatable side effects of urinary retention and urinary tract infections. |
| The SOAP-II trial: First-line vasopressor for shock management | 2010 | NEJM | 320 | 1. There were no significant differences in 28-day, 6-month, or 12-month mortality when comparing dopamine and norepinephrine as first-line vasopressors in managing shock 2. Dopamine was associated with a significantly higher rate of arrhythmias, as well as severe arrhythmias that required stopping the study drug, when compared to norepinephrine |
| The EINSTEIN-DVT trial: Rivaroxaban in acute deep-vein thrombosis | 2010 | NEJM | 320 | 1. Rivaroxaban is non-inferior to standard therapy of enoxaparin and vitamin K antagonist in treating acute, symptomatic deep-vein thrombosis 2. The risk of major and clinically relevant nonmajor bleeding was not significantly different when comparing rivaroxaban with standard therapy |
| The DAPT trial: Extended dual antiplatelet therapy after drug eluting stents | 2014 | NEJM | 319 | 1. After 12 months of dual antiplatelet therapy in patients who received drug eluting stents (DES), patients who continued on a thienopyridine in addition to aspirin for 18 months experienced significantly lower rates of stent thrombosis and myocardial infarction compared to those taking placebo. 2. The risk of bleeding was significantly higher in patients who continued on thienopyridine therapy. |
| Prednisolone vs placebo in severe alcoholic hepatitis | 1992 | NEJM | 312 | 1. Compared to placebo, treating patients with severe alcoholic hepatitis with 28 days of prednisolone significantly improved the short-term survival up to 6 months. 2. There remains significant controversy surrounding the use of glucocorticoids in managing severe alcoholic hepatitis, as numerous other trials have demonstrated no mortality benefit, but significantly higher risk of infection with glucocorticoid therapy. |
| Ceftriaxone vs. norfloxacin for prophylaxis in patients with cirrhosis and gastrointestinal bleeding | 2006 | Gastroenterology | 300 | 1. In cirrhotic patients who presented with gastrointestinal bleeding, patients treated with ceftriaxone were significantly less likely to develop proved or possible infections when compared to those treated with norfloxacin. 2. The ceftriaxone group was also significantly less likely to developed proved infections or spontaneous bacteremia and bacterial peritonitis. 3. There were no significant differences between the two groups in 10-day or hospital mortality. |
| Vaginal progesterone for sonographic short cervix decreases preterm birth | 2011 | Ultrasound in Obstetrics & Gynecology | 293 | 1. Among women with a sonographic short cervix, those randomized to receive daily vaginal progesterone were 45% less likely to experience preterm delivery prior to 33 weeks gestation (NNT=14). 2. Adverse neonatal outcomes including respiratory distress syndrome (NNT=22), low birthweight and neonatal mortality were significantly less common in the vaginal progesterone group. |
| The PANTER trial: Open necrosectomy vs step-up approach for necrotizing pancreatitis | 2010 | NEJM | 284 | 1. A minimally invasive step-up approach significantly reduced the rate of major complications as compared to open necrosectomy in patients with necrotizing pancreatitis |
| The PROSEVA trial: Proning in severe ARDS | 2013 | NEJM | 280 | 1. In patients with severe acute respiratory distress syndrome (ARDS), prone-positioning significantly reduced 28-day and 90-day mortality when compared with patients remaining in supine position. 2. Proned patients were also successfully extubated at higher rates and required fewer days of ventilation when compared to supine patients. |
| The RACE-II trial: Lenient vs. strict rate-control in atrial fibrillation | 2010 | NEJM | 262 | 1. Lenient rate-control was found to be non-inferior to strict rate-control in managing patients with atrial fibrillation 2. Compared to strict rate-control, lenient rate-control could be achieved with lower doses of medication and fewer medications |
| Dexamethasone effective as initial therapy for immune thrombocytopenic purpura | 2003 | NEJM | 259 | 1. Of 125 patients with newly diagnosed immune thrombocytopenic purpura, 106 (85%) had an initial response to high-dose dexamethasone therapy 2. Half of the 106 patients with an initial response to high-dose dexamethasone had a sustained response after six months of follow-up |
| Omeprazole before endoscopy in patients with gastrointestinal bleeding | 2007 | NEJM | 254 | 1. Compared to placebo, treating patients with omeprazole bolus and infusion prior to endoscopy significantly reduces the need for endoscopic therapy, the rate of post-endoscopy active bleeding, and shortens hospital stays. 2. Treating patients with omeprazole pre-endoscopy did not significantly reduce the need for emergency surgery and did not reduce 30-day mortality as compared with placebo. |
| Cesarean delivery for term breech not associated with long-term benefit | 2004 | AJOG | 252 | 1. At 2-year follow-up, planned cesarean delivery was not associated with reduction in neurodevelopmental delay compared to planned vaginal delivery for term breech malpresentation. |
| The AMPLIFY trial: Apixaban for treatment of venous thromboembolism | 2013 | NEJM | 238 | 1. Apixaban was found to be non-inferior to conventional therapy (i.e., enoxaparin followed by warfarin) in the treatment of acute venous thromboembolism. 2. Major bleeding was found to be significantly less common in patients treated with apixaban as compared with conventional therapy. |
| Magnesium reduces cerebral palsy in infants delivered early preterm | 2008 | NEJM | 238 | 1. Among women with imminent delivery between 24 and 31 weeks gestation, those randomized to receive magnesium sulfate experienced a decreased risk of moderate or severe cerebral palsy. 2. Risk of fetal death did not differ between groups. |
| Early TIPS in cirrhosis and variceal bleeding | 2010 | NEJM | 231 | 1. In patients with severe liver disease and variceal bleeding, early transjugular intrahepatic portosystemic shunt (TIPS) significantly reduced the rate of treatment failure, length of hospitalization, and mortality 2. Early TIPS was not associated with a difference in the rate of adverse events compared to control |
| The EVAR I trial: Endovascular vs. open abdominal aortic aneurysm repair | 2010 | NEJM | 227 | 1. The EVAR I trial compared the safety and efficacy of endovascular and open abdominal aortic aneurysm repair 2. There were no significant differences in all-cause mortality between the two groups 3. The endovascular group experienced significantly higher rates of graft-related complications and reinterventions |
| Worse side effects following transobturator sling | 2010 | NEJM | 225 | 1. Retropubic tension free vaginal tape (TVT) and transobturator tape (TOT) were associated with similar success rates for treatment of stress urinary incontinence at one year. 2. TOT was associated with worrisome side effects like obturator neuropathies, while TVT was associated with more readily preventable and treatable side effects of urinary retention and urinary tract infections. |
| Cerclage prevents recurrent preterm birth in women with short cervix | 2009 | AJOG | 205 | 1. In women with a history of prior preterm birth less and midtrimester cervical length <25mm, cerclage reduced perinatal morbidity and preterm delivery at less than 24 weeks. 2. In women with midtrimester cervical length <15mm, cerclage reduced preterm birth less than 35 weeks. |
| Initial trial of conservative management of splenic injury | 1971 | Journal of Pediatric Surgery | 202 | 1. The conservative, symptomatic management of 16 patients following assumed splenic injury from blunt abdominal trauma resulted in normalization of hemodynamic stability within 2 days of hospital admission, complete normalization of clinical examination by 2 weeks post-discharge, and no hospital readmissions 2. This approach to splenic injury management was later supported by future investigations, eventually leading to the acceptance of conservative management as standard of care |
| Antibiotic prophylaxis not associated with UTI prevention in children | 2008 | Journal of Urology | 201 | 1. Among children recruited following febrile urinary tract infection (UTI) and randomized to receive either antibiotics or no medication, no significant difference in UTI recurrence was noted between groups 2. Male children and those with grade III vesicoureteral reflex had significant reductions in subsequent UTIs if treated with prophylactic antibiotics |
| Prediction rules for children at low risk of clinically-important traumatic brain injury | 2009 | Lancet | 192 | 1. Absence of six established predictors was found to have close to 100% negative predictive value for clinically-important traumatic brain injury (ciTBI) when applied to head trauma patients under 18 years of age 2. An algorithm was proposed, applying these predictors, in order to prevent physicians from using unnecessary computed tomography (CT) in pediatric patients at low risk for ciTBI |
| The CRASH-II trial: Tranexamic acid in trauma patients | 2010 | Lancet | 190 | 1. Tranexamic acid significantly reduces all-cause mortality in trauma patients with significant hemorrhage 2. There were no significant differences between the tranexamic acid and placebo groups with regards to the incidence of vascular occlusive events or the need for transfusion or surgery |
| Preterm infants benefit from delayed umbilical cord clamping | 1993 | BMJ | 186 | 1. Preterm infants randomized to delayed cord clamping for 30 seconds after birth required less cardiorespiratory intervention, less supplemental oxygen and fewer blood transfusions compared to controls. |
| The ATLAS trial: Duration of adjuvant tamoxifen in ER-positive breast cancer | 2013 | Lancet | 171 | 1. Among women with early ER-positive breast cancer, continuing adjuvant tamoxifen for 10 years versus stopping at 5 years after diagnosis significantly reduced breast cancer recurrence, breast cancer mortality, and overall mortality 2. Patients treated with adjuvant tamoxifen for 10 years had significantly higher risk of endometrial cancer and pulmonary embolism |
| The PRECOMBAT trial: PCI vs. CABG in left main coronary artery stenosis | 2011 | NEJM | 162 | 1. For patients with left main coronary artery stenosis, angioplasty with sirolimus-eluting stents was noninferior to coronary artery bypass grafting with respect to subsequent cardiovascular or cerebrovascular events 2. PCI patients experienced a significantly higher incidence of ischemia-driven target vessel revascularization compared to CABG patients 3. Because of low event rates, the study was underpowered |
| The PIVOT trial: Radical prostatectomy versus observation | 2012 | NEJM | 160 | 1. Prostatectomy did not significantly reduce all-cause mortality or prostate-cancer mortality when compared to observation 2. These findings support conservative management for men with localized prostate cancer, especially for those with PSA values less than 10 ng/mL and low-risk disease |
| The ICAP trial: Colchicine in acute pericarditis | 2013 | NEJM | 157 | 1. Colchicine has been commonly used in the treatment of inflammatory conditions, including gout and serositis. 2. This study demonstrated that colchicine, in addition to standard therapy, significantly reduced the risk of incessant or recurrent pericarditis compared to placebo. 3. There were no significant differences between colchicine and placebo in the risk of gastrointestinal side effects. |
| The AREDS2: No benefit from additional carotenoid and omega-3-fatty acid supplementation to original AREDS formulation | 2013 | JAMA | 154 | 1. There was no added benefit observed with adding lutein and zeaxanthin, omega-3-fatty acids (DHA and EPA), or the combination to the original AREDS formulation in reducing progression to advanced age-related macular degeneration (AMD) in high-risk patients. 2. Because of the suspected association between beta-carotene and increased lung cancer risk in smokers, beta-carotene can be replaced by lutein and zeaxanthin in recent and current smokers requiring AREDS supplementation. |
| Decrease in symptom severity linked to infliximab Crohn’s treatment | 2000 | Journal of Pediatrics | 152 | 1. The severity of Crohn’s disease as assessed by the Pediatric Crohn’s Disease Activity Index in patients recruited from 3 pediatric specialty centers decreased significantly over the course of a 12-week treatment regimen with infliximab 2. All patients were on corticosteroids at the start of the study; however, steroid administration decreased significantly over the course of the investigation |
| The PLCO trial 2: Flexible sigmoidoscopy in colon cancer screening | 2012 | NEJM | 151 | 1. Screening with flexible sigmoidoscopy is associated with a significant decrease in colon cancer incidence in the distal and proximal colon 2. Screening with flexible sigmoidoscopy is associated with a significant decrease in colon cancer mortality in the distal colon only |
| The EINSTEIN-PE trial: Rivaroxaban to treat pulmonary embolism | 2012 | NEJM | 148 | 1. Rivaroxaban, an oral factor Xa inhibitor, was non-inferior to standard anticoagulation therapy (i.e. low-molecular weight heparin and a vitamin K antagonist) in the prevention of recurrent thromboembolism following a pulmonary embolism 2. The rate of major bleeding was significantly lower with rivaroxaban than with standard anticoagulant therapy |
| RSV positivity associated with reduced serious bacterial infection risk | 2004 | Pediatrics | 126 | 1. RSV-positive infants were significantly less likely to have an SBI than those who tested negative (7% vs. 12.5%, RR 0.6, p < .05) and at reduced risk for SBI (OR 0.58) 2. Infants <28 days old were significantly more likely to have an SBI than older infants (10.1% vs. 5.5%) |
| Clinical prediction rule stratifies pediatric bacterial meningitis risk | 2002 | Pediatrics | 126 | 1. A Bacterial Meningitis Score of 0 accurately identified all children with aseptic meningitis in the study’s validation group 2. The negative predictive value of a BMS score of 0 was 100% with a specificity of 73% in predicting bacterial meningitis. A BMS score of >2 was found to have a sensitivity and positive predictive value of 87% in predicting bacterial meningitis |
| Symptom-triggered benzodiazepine treatment for alcohol withdrawal | 2002 | Archives of Internal Medicine | 119 | 1. For patients withdrawing from alcohol, a symptom-triggered pharmacologic therapy may decrease detoxification time without compromising the safety or comfort of the patient 2. Symptom-triggered individualized benzodiazephine administration reduces the intensity and duration of oxazepam use during withdrawal treatment |
| HPV triage is optimal management for ASCUS | 2003 | AJOG | 118 | 1. A single human papillomavirus (HPV) test identified 92.4% of women diagnosed with CIN-III. 2. A strategy of HPV triage testing detected high-grade intraepithelial lesion (HSIL) with 72% sensitivity, compared to 54% with immediate colposcopy and 55% with conservative management strategies. 3. In the HPV triage arm, 56% of women were referred for colposcopy whereas 100% and 12% of women in the immediate colposcopy and conservative management arms, respectively, underwent cervical biopsy. |
| Initial guidelines for prolonged fever in children | 1975 | Pediatrics | 112 | 1. Among 100 children presenting to one children’s hospital for prolonged febrile illnesses, the majority of cases were of an infectious etiology (52 cases) 2. Significantly more febrile illnesses in younger children were due to infectious causes, while those due to inflammatory conditions were significantly more likely to occur in older children |
| The LACTATE trial: Early lactate-guided therapy in intensive care patients | 2010 | AJRCCM | 110 | 1. Therapy aimed at reducing lactate levels by 20% every 2 hours during the first 8 hours of ICU admission led to decreased in-hospital mortality and shorter ICU stays 2. Patients in the early lactate-guided therapy group received more fluids and started on vasopressors earlier than in the control group, but did not have a faster reduction rate of lactate levels |
| Transcutaneous bilirubinometry linked to decreased serum testing and costs | 1997 | Pediatrics | 69 | 1. In a 2 year study period, researchers observed a significant decrease in the number of infants undergoing bilirubin serum testing after introduction of a transcutaneous bilirubinometer in one hospital’s newborn nursery 2. The use of the transcutaneous instrument decreased hospital costs by $1625 each year when compared to serum bilirubin measurements |
| The DEFINE trial: BG-12 reduces relapse rate in multiple sclerosis | 2012 | NEJM | 63 | 1. BG-12 (dimethyl fumarate) significantly reduces relapse rates, disability progression, and image detectable lesion load over a two-year period 2. BG-12 is associated with higher rates of transient flushing and gastrointestinal events |
| The EVAR II trial: Endovascular approach when unfit for open aortic aneurysm repair | 2010 | NEJM | 50 | 1. The EVAR II trial compared endovascular abdominal aortic aneurysm repair with no intervention in patients unsuitable for the open procedure 2. There were significantly fewer aneurysm-related deaths in the endovascular group, compared to no intervention 3. The rates of complication and reintervention were similar to the rates observed in EVAR I |
| The BRIDGE trial: Periprocedural bridging in patients with atrial fibrillation | 2015 | NEJM | 44 | 1. Patients with atrial fibrillation are often treated with long-term oral anticoagulation, and may require interruption of their anticoagulation for elective surgeries or invasive procedures. 2. This study demonstrated that periprocedural bridging with dalteparin did not significantly reduce the risk of arterial thromboembolic disease when compared to placebo. 3. Patients treated with bridging dalteparin experienced significantly higher risk of major and minor bleeding. |
| Twin vaginal delivery as safe as cesarean | 2013 | NEJM | 39 | 1. Among women with cephalic-presenting diamniotic twins at term, those randomized to planned cesarean delivery were not more likely to experience adverse neonatal outcomes compared to those randomized to planned vaginal delivery. 2. Compared to planned vaginal delivery, scheduled elective cesarean delivery conferred no more than a 23% reduction and no more than a 74% increase in the odds of neonatal death or serious morbidity. 3. There was no difference in the incidence of the composite outcome for maternal morbidity and mortality between women assigned to planned Cesarean compared and those randomized to planned vaginal delivery. |
| Isolated thrombocytopenia uncommon in children treated for ALL | 1989 | Pediatrics | 39 | 1. Among 2239 pediatric patients diagnosed with acute lymphoblastic leukemia, no child met criteria for isolated thrombocytopenia as evidenced by complete blood count, peripheral blood smear, and hepatosplenomegaly on physical exam |
| The EVS: Vitrectomy results in better visual outcomes for light-perception patients | 1995 | JAMA Ophthalmology | 20 | 1. In patients with endophthalmitis after recent lens implantation, immediate vitrectomy significantly improved visual outcomes for patients presenting with light-perception visual acuity compared to vitreous tap. In patients with better than light-perception vision at the time of presentation, there was no benefit with vitrectomy. 2. Systemic antibiotics do not provide any further benefit when added to intraocular antibiotics in either vitrectomy or vitreous tap. |
| The SOME trial: Screening for occult malignancy in unprovoked venous thromboembolism | 2015 | NEJM | 16 | 1. Patients with a first unprovoked venous thromboembolism were randomized to either limited-screening for occult malignancy or limited-screening plus computed tomography (CT) of the abdomen and pelvis. 2. There were no significant differences between the two strategies in the number of occult malignancies diagnosed, and the number of occult malignancies missed by the initial screen. |
| Letrozole superior to clomid for ovulation induction in PCOS | 2014 | NEJM | 12 | 1. Women with polycystic ovary syndrome (PCOS) randomized to receive letrozole had more live births than women randomized to clomiphene (27.5% vs. 19.1%, p=0.007). 2. Cumulative ovulation rates were higher in women on letrozole compared to those on clomiphene (61.7% vs. 48.3%, p<0.001). |
| Most ovarian cysts resolve, sonographic surveillance recommended | 2013 | Obstetrics & Gynecology | 6 | 1. The majority (>60%) of ovarian abnormalities, even complex, solid or bilateral cysts, resolved with serial ultrasounds. 2. Complex-appearing cysts resolved more quickly than simple-appearing cysts (8.7 weeks vs. 53.0 weeks, to resolution, respectively, p<0.01). 3. The positive predictive value associated with serial ultrasounds is 24.7% compared to 8.1% with a single ultrasound. |
| Clinical decision rule associated with 40% decrease in ALTE-related hospital admissions | 2012 | Pediatric Emergency Care | 5 | 1. Abnormal physical exam findings, prematurity, cyanosis, absence of upper respiratory infection (URI), and absence of choking were significant predictors of the need for significant intervention among study participants admitted for hospitalization following apparent life-threatening events (ALTEs) 2. A clinical decision rule (CDR) was designed and validated that would have reduced ALTE-related hospital admission in this sample by 40% |
| The BHAT: Propranolol after acute myocardial infarction | 1982 | JAMA | 0 | 1. Beta-blockers were commonly used in the treatment of coronary artery disease in the 1980s, though prior studies were inconclusive due to limitations in study design and small sample sizes. 2. This was the first large, randomized trial to demonstrate that propranolol significantly reduced mortality after acute myocardial infarction when compared with placebo. |
| The LRC-CPPT 1: Cholestyramine and coronary heart disease | 1984 | JAMA | 0 | 1. In the 1970s, observational data suggested a direct link between serum cholesterol levels and the risk of coronary heart disease (CHD). 2. This trial was one of the first large, randomized studies to demonstrate that reducing lipid levels with cholestyramine could significantly lower death from CHD and nonfatal myocardial infarction, when compared to placebo. |