Aspirin and Hemocompatibility After LVAD Implantation in Patients With Atherosclerotic Vascular Disease: A Secondary Analysis From the ARIES-HM3 Randomized Clinical Trial

Abstract

Importance: The Aspirin and Hemocompatibility Events With a Left Ventricular Assist Device in Advanced Heart Failure (ARIES-HM3) study demonstrated that aspirin may be safely eliminated from the antithrombotic regimen after HeartMate 3 (HM3 [Abbott Cardiovascular]) left ventricular assist device (LVAD) implantation. This prespecified analysis explored whether conditions requiring aspirin (prior percutaneous coronary intervention [PCI], coronary artery bypass grafting [CABG], stroke, or peripheral vascular disease [PVD]) would influence outcomes differentially with aspirin avoidance.

Objective: To analyze aspirin avoidance on hemocompatibility-related adverse events (HRAEs) at 1 year after implant in patients with a history of CABG, PCI, stroke, or PVD.

Design, setting, and participants: This was an international, multicenter, prospective, double-blind, placebo-controlled, randomized clinical trial including patients implanted with a de novo HM3 LVAD across 51 centers. Data analysis was conducted from April to July 2024.

Interventions: Patients were randomized in a 1:1 ratio to receive aspirin (100 mg per day) or placebo, in addition to a vitamin K antagonist (VKA) targeted to an international normalized ratio of 2 to 3 in both groups.

Main outcomes and measures: Primary end point (assessed for noninferiority) was a composite of survival free of any nonsurgical (>14 days after implant) HRAEs including stroke, pump thrombosis, bleeding, and arterial peripheral thromboembolism at 12 months. Secondary end points included nonsurgical bleeding, stroke, and pump thrombosis events.

Results: Among 589 of 628 patients (mean [SD] age, 57.1 [13.7] years; 456 male [77.4%]) who contributed to the primary end point analysis, a history of PCI, CABG, stroke, or PVD was present in 41% (240 of 589 patients). There was no interaction between the presence of an atherosclerotic vascular condition and effect of aspirin compared with placebo (P for interaction= .23). The preset 10% noninferiority margin was not crossed for the studied subgroup of patients. Thrombotic events were rare, with no differences between aspirin and placebo in patients with and without vascular disease (P for interaction = .77). Aspirin treatment was associated with a higher rate of nonsurgical major bleeding events in the group with prior vascular condition history compared with those without aspirin (rate ratio for placebo compared with aspirin, 0.52; 95% CI, 0.35-0.79).

Conclusions and relevance: Results of this prespecified analysis of the ARIES-HM3 randomized clinical trial demonstrate that in patients with advanced heart failure who have classical indications for antiplatelet therapy use at the time of LVAD implantation, aspirin avoidance was safe and not associated with increased thrombosis risk. Importantly, elimination of aspirin was associated with no increased thrombosis but a reduction in nonsurgical bleeding events in patients with a history of PCI, CABG, stroke, or PVD.

Trial registration: ClinicalTrials.gov Identifier: NCT04069156.

Figure 1.. Flow Diagram of the Study Detailing Patients With and Without a History of Percutaneous Coronary Intervention (PCI), Coronary Artery Bypass Grafting (CABG), Stroke, or Peripheral Vascular Disease (PVD)

Patients who were enrolled and randomized in the Aspirin and Hemocompatibility Events With a Left Ventricular Assist Device in Advanced Heart Failure (ARIES-HM3) study were identified by the presence of at least one of the following prior conditions: PCI, CABG, stroke, or PVD. HM3 indicates HeartMate 3 (Abbott Cardiovascular); LVAD, left ventricular assist device.

Figure 2.. Incidence of the Primary End Point and Thrombotic Events in Patients With and Without a History of Percutaneous Coronary Intervention (PCI), Coronary Artery Bypass Grafting (CABG), Stroke, or Peripheral Vascular Disease (PVD) Assigned to Aspirin or Placebo

A, With respect to the primary end point, there was no interaction between presence of any of the arterial vascular conditions and effect of aspirin compared with placebo (P for interaction = .23). The vertical dashed line indicates the noninferiority margin. B, Thrombotic events during follow-up were rare in both groups, and there was no indication of a difference between aspirin and placebo (P for interaction = .77). The primary end point was the survival free of hemocompatibility-related adverse events: stroke, pump thrombosis, major nonsurgical bleeding, and arterial peripheral thromboembolism. This excluded patients who were withdrawn from study drug treatment before experiencing primary end point.

Figure 3.. Cumulative Hazard Rates for Moderate or Severe Nonsurgical Bleeding Events Stratified by History of Percutaneous Coronary Intervention (PCI), Coronary Artery Bypass Grafting (CABG), Stroke, or Peripheral Vascular Disease (PVD)

Although the cumulative incidence of nonsurgical major bleeding events was higher in the group with a prior history of PCI, CABG, stroke, or PVD, the increased rate of bleeding events in the group with a history of vascular disease was due to randomization to aspirin: the rate ratio (RR) for placebo compared with aspirin was 0.52 (95% CI, 0.35-0.79), whereas the difference in bleeding between aspirin and placebo was attenuated for patients without a history of PCI, CABG, stroke, or PVD with an RR of 0.76 (95% CI, 0.54-1.06).

Figure 4.. Time-to-Event Analysis of the Primary End Point Stratified by History of Percutaneous Coronary Intervention (PCI), Coronary Artery Bypass Grafting (CABG), Stroke, or Peripheral Vascular Disease (PVD)

The survival free from death and nonsurgical hemocompatibility-related adverse event analysis reported a significant reduction in hazard ratio (HR) between aspirin and placebo for patients with prior indication for aspirin (HR, 0.63; 95% CI, 0.41-0.98; P = .04) but not in patients without such indication (HR, 0.79; 95% CI, 0.54-1.15; P = .22).