Aspirin and left ventricular assist devices: rationale and design for the international randomized, placebo-controlled, non-inferiority ARIES HM3 trial

Abstract

Aims: Over decades, left ventricular assist device (LVAD) technology has transitioned from less durable bulky pumps to smaller continuous-flow pumps which have substantially improved long-term outcomes and quality of life. Contemporary LVAD therapy is beleaguered by haemocompatibility-related adverse events including thrombosis, stroke and bleeding. A fully magnetically levitated pump, the HeartMate 3 (HM3, Abbott, USA) LVAD, has been shown to be superior to the older HeartMate II (HMII, Abbott, USA) pump by improving haemocompatibility. Experience with the HM3 LVAD suggests near elimination of de-novo pump thrombosis, a marked reduction in stroke rates, and only a modest decrease in bleeding complications. Since the advent of continuous-flow LVAD therapy, patients have been prescribed a combination of aspirin and anticoagulation therapy on the presumption that platelet activation and perturbations to the haemostatic axis determine their necessity. Observational studies in patients implanted with the HM3 LVAD who suffer bleeding have suggested a signal of reduced subsequent bleeding events with withdrawal of aspirin. The notion of whether antiplatelet therapy can be avoided in an effort to reduce bleeding complications has now been advanced.

Methods: To evaluate this hypothesis and its clinical benefits, the Antiplatelet Removal and Hemocompatibility Events with the HeartMate 3 Pump (ARIES HM3) has been introduced as the first-ever international prospective, randomized, double-blind and placebo-controlled, non-inferiority trial in a patient population implanted with a LVAD.

Conclusion: This paper reviews the biological and clinical role of aspirin (100 mg) with LVADs and discusses the rationale and design of the ARIES HM3 trial.

Trial registration: ClinicalTrials.gov NCT04069156.

Keywords: Advanced heart failure; Aspirin; Assist devices; Bleeding; Hemocompatibility; LVAD; Mechanical Circulatory Support; Outcomes.

Figure 1

Residual risk of haemocompatibility‐related adverse effects with the HeartMate 3 (HM3) left ventricular assist device (LVAD). The figure depicts estimated hazard rates for device thrombosis, stroke and bleeding events in the HM3 arm of the MOMENTUM 3 pivotal trial. Hazard rates to first event are calculated using kernel‐smoothed hazard function. With the HM3, pump thrombosis has become a rare event. For stroke and bleeding, >75% of the cumulative hazard occurs within the first year of LVAD support, representing the greatest opportunity to reduce residual risk in HM3 patients.

Figure 2

The ARIES HM3 study flow diagram. ASA, aspirin; EDC, electronic data capture; HM3, HeartMate 3; ICF, informed consent form; INR, international normalized ratio.