Aspirin and Hemocompatibility Events in Chronic Advanced Heart Failure Patients with Assist Device

Overview

Heart failure is a world epidemic. LVADs are increasingly used as they have demonstrated improved survival rates compared to optimal medical management. Improving outcomes have been seen with the newer LVAD technology, the HeartMate 3 (Abbott, Chicago, IL), however, hemocompatibility related adverse events, including thrombosis and bleeding, are still a major cause of morbidity and mortality. The recent ARIES trial showed that in patients with advanced heart failure treated with a HeartMate3 LVAD, avoidance of aspirin as part of an antithrombotic regimen, which includes vitamin K antagonist (VKA), is not inferior to a regimen containing aspirin, does not increase thromboembolism risk, and is associated with a reduction in bleeding events. This clinical investigation is a prospective, randomized, controlled study of advanced heart failure patients supports with the HeartMate3 for more then 3 months with two different antithrombotic regimens: VKA with and without aspirin. The objective of this investigation is to study the safety and efficacy of an antithrombotic regimen without antiplatelet therapy.

Objective: To study the safety and efficacy of an anti-platelet-free antithrombotic regimen in patients with advanced heart failure who are chronically supported with the HeartMate 3 LVAD. Hypothesis: The withdrawal of aspirin from the antithrombotic regimen of HeartMate3 LVAD patients will not adversely affect safety and efficacy and may reduce non-surgical bleeding. Clinical Investigation Design: This is a prospective, randomized, controlled clinical investigation of advanced heart failure patients who are chronically supported with the HeartMate 3 LVAD. The study will compare two different antithrombotic regimens: VKA with aspirin versus VKA without aspirin. End points: Primary end point: * Composite of Survival free of any major hemocompatibility related adverse event at 1-year post randomization. 1. Major Hemocompatibility Related Adverse Event: Stroke, Pump Thrombosis (suspected or confirmed), major non surgical Bleeding (moderate or severe) (including intracranial bleeds that do not meet the stroke definition), Arterial Peripheral Thromboembolism Secondary end point: * Non-surgical Major Hemorrhagic Events * Non-surgical Major Thrombotic Events * Survival * Stroke Rates * Pump Thrombosis Rates * Bleeding Rates, including: * Non-surgical Bleeding * Moderate Bleeding * Severe Bleeding * Fatal Bleeding * GI Bleeding Descriptive endpoints * Hemocompatibility score: a tiered hierarchal score that weighs each hemocompatibility related adverse event by its escalating clinical relevance⁸ * Rehospitalizations * Economic Cost Implications * Subgroup analysis (patients with increased bleeding/thrombotic risk (i.e prior HRAE events) Number of Subjects Required for Inclusion in Clinical Investigation: Based on ARIES results, 58 patients will need to be enrolled in each arm (116 total) to achieve 80% power to prove that the non-aspirin group is non-inferior to the aspirin group using a non-inferiority margin of 15% with the Farrington-Manning risk difference approach to non-inferiority at a one-sided alpha = 0.05. To account for an expected 10% dropout rate, up to 128 patients will be randomized in the trial.