IMPORTANCE: Left ventricular assist devices (LVADs) enhance quality and duration of life in advanced heart failure. The burden of nonsurgical bleeding events is a leading morbidity. Aspirin as an antiplatelet agent is mandated along with vitamin K antagonists (VKAs) with continuous-flow LVADs without conclusive evidence of efficacy and safety. OBJECTIVE: To determine whether excluding aspirin as part of the antithrombotic regimen with a fully magnetically levitated LVAD is safe and decreases bleeding. DESIGN, SETTING, AND PARTICIPANTS: This international, randomized, double-blind, placebo-controlled study of aspirin (100 mg/d) vs placebo with VKA therapy in patients with advanced heart failure with an LVAD was conducted across 51 centers with expertise in treating patients with advanced heart failure across 9 countries. The randomized population included 628 patients with advanced heart failure implanted with a fully magnetically levitated LVAD (314 in the placebo group and 314 in the aspirin group), of whom 296 patients in the placebo group and 293 in the aspirin group were in the primary analysis population, which informed the primary end point analysis. The study enrolled patients from July 2020 to September 2022; median follow-up was 14 months. INTERVENTION: Patients were randomized in a 1:1 ratio to receive aspirin (100 mg/d) or placebo in addition to an antithrombotic regimen. MAIN OUTCOMES AND MEASURES: The composite primary end point, assessed for noninferiority (-10% margin) of placebo, was survival free of a major nonsurgical (>14 days after implant) hemocompatibility-related adverse events (including stroke, pump thrombosis, major bleeding, or arterial peripheral thromboembolism) at 12 months. The principal secondary end point was nonsurgical bleeding events. RESULTS: Of the 589 analyzed patients, 77% were men; one-third were Black and 61% were White. More patients were alive and free of hemocompatibility events at 12 months in the placebo group (74%) vs those taking aspirin (68%). Noninferiority of placebo was demonstrated (absolute between-group difference, 6.0% improvement in event-free survival with placebo [lower 1-sided 97.5% CI, -1.6%]; P < .001). Aspirin avoidance was associated with reduced nonsurgical bleeding events (relative risk, 0.66 [95% confidence limit, 0.51-0.85]; P = .002) with no increase in stroke or other thromboembolic events, a finding consistent among diverse subgroups of patient characteristics. CONCLUSIONS AND RELEVANCE: In patients with advanced heart failure treated with a fully magnetically levitated LVAD, avoidance of aspirin as part of an antithrombotic regimen, which includes VKA, is not inferior to a regimen containing aspirin, does not increase thromboembolism risk, and is associated with a reduction in bleeding events. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04069156.

Abbott Chicago Illinois

Allegheny Health Network Pittsburgh Pennsylvania

Baptist Health Medical Center Little Rock Arkansas

Baylor University Hospital Dallas Texas

Brigham and Women's Hospital and Harvard Medical School Boston Massachusetts

Columbia University College of Physicians and Surgeons and New York Presbyterian Hospital New York

Duke University Medical Center Durham North Carolina

Emory University Hospital Atlanta Georgia

Henry Ford Hospital Detroit Michigan

Institute for Clinical and Experimental Medicine Prague Czech Republic

Kansas University Medical Center Kansas City

Medical University of Vienna Vienna Austria

Medstar Washington Hospital Center Washington DC

Miami Transplant Institute Jackson Memorial Miami Florida

Montefiore Einstein Center for Heart and Vascular Care New York New York

National Research Center for Cardiac Surgery Kazakhstan

Ochsner Medical Center New Orleans Louisiana

Rigshospitalet University of Copenhagen Copenhagen Denmark

The Cleveland Clinic Foundation Cleveland Ohio

University of Michigan Ann Arbor

University of Minnesota Medical Center Fairview Minneapolis

University of North Carolina at Chapel Hill Chapel Hill

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Metabolic Consequences of Advanced Chronic Heart Failure and its Modification by Implantation of a Durable Left Ventricular Assist Device

Drug therapy and catheter ablation for management of arrhythmias in continuous flow left ventricular assist device's patients: a Clinical Consensus Statement of the European Heart Rhythm Association and the Heart Failure Association of the ESC

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ClinicalTrials.gov
NCT04069156