Heart Rhythm Clinical Trials

The RE-LY Trial (Randomized Evaluation of Long-Term Anticoagulation Therapy, 2009): In patients with AF, dabigatran given at a dose of 110 mg was associated with rates of stroke and systemic embolism that were similar to those associated with warfarin, as well as lower rates of major hemorrhage. Dabigatran administered at a dose of 150 mg, as compared with warfarin, was associated with lower rates of stroke and systemic embolism but similar rates of major hemorrhage.
https://doi.org/10.1056/nejmoa0905561

The ROCKET AF Trial (The Rivaroxaban Once Daily Oral Direct Factor Xa Inhibition Compared with Vitamin K Antagonism for Prevention of Stroke and Embolism Trial in Atrial Fibrillation, 2011): In patients with atrial fibrillation, rivaroxaban (factor Xa inhibition) was noninferior to warfarin (vitamin K antagonists) for the prevention of stroke or systemic embolism.
https://doi.org/10.1056/nejmoa1009638

The AVERROES Trial (Apixaban Versus Acetylsalicylic Acid [ASA] to Prevent Stroke in Atrial Fibrillation Patients Who Have Failed or Are Unsuitable for Vitamin K Antagonist Treatment, 2011):   In patients with atrial fibrillation for whom vitamin K antagonist therapy was unsuitable, apixaban reduced the risk of stroke or systemic embolism without significantly increasing the risk of major bleeding or intracranial hemorrhage. 
https://doi.org/10.1056/nejmoa1007432

The ARISTOTLE Trial (Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation, 2011):   In patients with atrial fibrillation, apixaban was superior to warfarin in preventing stroke or systemic embolism, caused less bleeding, and resulted in lower mortality. 
https://doi.org/10.1056/nejmoa1107039

The ENGAGE AF-TIMI Trial (The Effective Anticoagulation with Factor Xa Next Generation in Atrial Fibrillation–Thrombolysis in Myocardial Infarction, 2013):  Edoxaban, an oral, reversible, direct factor Xa inhibitor, was noninferior to warfarin with respect to the prevention of stroke or systemic embolism and was associated with significantly lower rates of bleeding and death from cardiovascular causes. 
https://doi.org/10.1056/nejmoa1310907

The CRYSTAL AF Trial (The Cryptogenic Stroke and Underlying AF, 2014):  ECG monitoring with an ICM was superior to conventional follow-up for detecting atrial fibrillation after stroke without a known cause. 
https://doi.org/10.1056/nejmoa1313600

The EAST-AFNET 4 Trial (Early Treatment of Atrial Fibrillation for Stroke Prevention Trial, 2020): Early rhythm control therapy led to a significant reduction in adverse cardiovascular outcomes when compared to the usual care strategy. 
https://www.nejm.org/doi/full/10.1056/NEJMoa2019422

The ARTESiA Trial (Apixaban for the Reduction of Thrombo-Embolism in Patients with Device-Detected Subclinical Atrial Fibrillation, 2023):   Among patients with subclinical atrial fibrillation, apixaban resulted in a lower risk of stroke or systemic embolism than aspirin but a higher risk of major bleeding.
https://doi.org/10.1056/nejmoa2310234

The AFFIRM Trial (Atrial Fibrillation Follow-up Investigation of Rhythm Management, 2002): A Comparison of Rate Control and Rhythm Control in Patients with Atrial Fibrillation.
https://www.nejm.org/doi/full/10.1056/NEJMoa021328

The CABANA Trial (Catheter Ablation vs Anti-arrhythmic Drug Therapy for Atrial Fibrillation, 2019): Catheter ablation was not significantly more effective than drug therapy at preventing death, disabling stroke, serious bleeding, or cardiac arrest.
https://doi.org/10.1001/jama.2019.0693

The RACE II Trial (Rate Control Efficacy in Permanent Atrial Fibrillation: a Comparison between Lenient versus Strict Rate Control II, 2010): In patients with permanent atrial fibrillation, lenient rate control is as effective as strict rate control and is easier to achieve.
https://www.nejm.org/doi/full/10.1056/NEJMoa1001337
 

The MADIT Trial (Multicenter Automatic Defibrillator Implantation Trial, 1996): In patients with a prior MI who are at high risk for VT, prophylactic therapy with an implanted defibrillator leads to improved survival as compared with conventional medical therapy.
https://doi.org/10.1056/nejm199612263352601

The MUSTT Trial (Multicenter UnSustained Tachycardia Trial, 1999 ) Electrophysiologically guided antiarrhythmic therapy with implantable defibrillators, but not with antiarrhythmic drugs, reduces the risk of sudden death in high-risk patients with coronary disease. 
https://doi.org/10.1056/nejm199912163412503

The MADIT II Trial (Multicenter Automatic Defibrillator Implantation Trial II, 2002): Implantable cardioverter-defibrillator (ICD) therapy is superior to conventional medical therapy in reducing the risk of death among patients with prior myocardial infarction and reduced ejection fraction.
https://www.nejm.org/doi/full/10.1056/NEJMoa013474

The SCD-HeFT Trial (Sudden Cardiac Death in Heart Failure Trial, 2005): In patients with heart failure and reduced ejection fraction, implantation of an ICD reduces all-cause mortality.
https://www.nejm.org/doi/full/10.1056/NEJMoa043399

The DAVID Trial (Dual Chamber and VVI Implantable Defibrillator Trial, 1996) For patients with standard indications for ICD therapy, no indication for cardiac pacing, and an LVEF of 40% or less, dual-chamber pacing offers no clinical advantage over ventricular backup pacing and may be detrimental by increasing the combined end point of death or hospitalization for heart failure. 
https://doi.org/10.1001/jama.288.24.3115

The MOST Trial (Mode Selection Trial in Sinus-Node Dysfunction, 2002):  For sinus-node dysfunction, while dual-chamber pacing does not improve stroke-free survival compared with ventricular pacing, dual-chamber pacing does reduce the risk of atrial fibrillation, signs and symptoms of heart failure, and slightly improves the quality of life.
https://doi.org/10.1056/nejmoa013040

The COMPANION Trial (Comparison of Medical Therapy, Pacing, and Defibrillation in Heart Failure, 2004):  In patients with advanced heart failure and a prolonged QRS interval, cardiac-resynchronization therapy decreases the combined risk of death from any cause or first hospitalization and, when combined with an ICD, significantly reduces mortality.
https://doi.org/10.1056/nejmoa032423

The CARE-HF Trial (Cardiac Resynchronization — Heart Failure, 2005):  In patients with heart failure and cardiac dyssynchrony, CRT improves symptoms and the quality of life and reduces complications and the risk of death. These benefits are in addition to those afforded by standard pharmacologic therapy. The implantation of a cardiac-resynchronization device should routinely be considered in such patients.
https://doi.org/10.1016/S1388-9842(01)00176-3

The MADIT-CRT Trial (Multicenter Automatic Defibrillator Implantation Trial–Cardiac Resynchronization Therapy, 2009):  CRT combined with ICD decreased the risk of heart-failure events in relatively asymptomatic patients with a low ejection fraction and wide QRS complex.
https://doi.org/10.1056/nejmoa0906431

The RAFT Trial (Resynchronization-Defibrillation for Ambulatory Heart Failure Trial, 2010): In patients with mild to moderate heart failure and a wide QRS complex, the addition of CRT to an ICD reduced rates of death and hospitalization.
https://www.nejm.org/doi/full/10.1056/NEJMoa1009540

The BLOCK-HF Trial (Biventricular versus Right Ventricular Pacing in Heart Failure Patients with Atrioventricular Block, 2013): Biventricular pacing was superior to conventional RV pacing in patients with AV block and LV systolic dysfunction with NYHA class I, II, or III heart failure. 
https://doi.org/10.1056/nejmoa1210356

The CAST Trial (Cardiac Arrhythmia Suppression Trial, 1989): Antiarrhythmic drugs flecainide and encainide may actually increase mortality in post-MI patients with asymptomatic ventricular arrhythmias. 
https://www.nejm.org/doi/full/10.1056/NEJM199103213241201