ARIES-HM3: Aspirin avoidance Is safe and reduces bleeding events in patients with HM3 LVAD on VKA

By Leah Kosyakovsky on

Key Points:

  • Since the advent of novel HeartMate 3 LVAD technology with lower thrombotic risk, the clinical utility of continuing to add aspirin to the antithrombotic strategy has not been established.
  • In the ARIES-HM3 study, an aspirin exclusion strategy (ie, Vitamin K antagonist [VKA] + placebo) was compared with the typical dual VKA/ASA therapy in patients with a HeartMate 3 LVAD. The primary endpoint was survival free of any non-surgical major hemocompatibility related adverse event one year post implant.
  • Aspirin avoidance resulted in fewer bleeding events and hospitalizations for bleeding complications without any concurrent increase in thrombosis or mortality.

The HeartMate 3 LVAD is a centrifugal-flow, magnetically levitated VAD which was designed to minimize hemolysis and thrombosis. While aspirin (ASA) is typically a mainstay of post-VAD implantation, it is unclear whether it is a clinically necessary addition to antithrombotic therapy in HeartMate 3 (HM3) patients. In a breaking presentation at the 2023 AHA Scientific Sessions today, Dr. Mandeep Mehra (BWH, Boston) and his team presented their study: “Aspirin and Hemocompatibility Events with a Left Ventricular Assist Device in Advanced Heart Failure,” or the ARIES-HM3 clinical trial.

The ARIES-HM3 trial (NCT04069156) was a prospective, randomized, double-blinded, placebo-controlled study of VKA therapy and ASA (100 mg/d) vs VKA therapy alone patients undergoing HM3 implantation. Participants were required to have undergone HM3 as their first durable VAD. Key exclusion criteria were pregnancy, the requirement of post implant additional temporary MCS, mandated antiplatelet therapy for other conditions, and those with a known ASA allergy. The primary outcome was a non-inferiority analysis of survival free of any non-surgical major hemocompatibility related adverse event at 1-year post implant. The principal secondary outcome was all non-surgical bleeding.

A total of 628 patients were 1:1 randomized across 51 international centers to either ASA or placebo, in addition to standard VKA therapy. Of those 589 were analyzed. The median age was 60, 22% were women, and there was a similar baseline prevalence of prior stroke (15% vs 12%) and bleeding (6% vs 4%) in the placebo vs ASA groups. More patients were alive and free of hemocompatibility events at 12 months in the placebo group (68%) vs those taking aspirin (74%). In the primary endpoint analysis, placebo was non-inferior to aspirin for survival free of major hemocompatibility-related adverse event at one year (6.0% difference, lower 97.5% CI-1.6% with a non-inferiority margin of -10%; p<0.001). Aspirin use resulted in a higher rate of non-surgical bleeding events (42.4% vs 30.0%, HR 0.67 [0.50-0.92], p=0.001). There were no differences in thrombosis or mortality (all p>0.05). Additionally, there were no differences in time in therapeutic range for VKA between the two groups (55.1% vs 58.9% for placebo vs ASA, p=0.93). In a US-population analysis, aspirin avoidance resulted in a 47% reduction in days hospitalized due to bleeding events, and a 41% reduction in cost of bleeding hospitalizations.

When discussing the clinical implications of the study at the Scientific Sessions, Dr. Mehra stated: “In patients with advanced heart failure receiving support from HeartMate 3 LVAD, aspirin is not required as part of an antithrombotic regimen that includes a Vitamin K Antagonist to preserve outcomes…exclusion of aspirin is associated with a significant decrease in bleeding events with no increase in thrombo-embolism.”