Key Points
Question: Can aspirin be safely avoided as part of an antithrombotic regimen including a vitamin K antagonist with a fully magnetically levitated left ventricular assist device (LVAD), and can such an approach reduce residual risk of nonsurgical bleeding complications?
Findings: In the ARIES-HM3 randomized trial of aspirin (100 mg/d) or placebo, avoidance of aspirin as part of an antithrombotic regimen that included a vitamin K antagonist in patients supported with an LVAD resulted in a significant decrease (34%) in major nonsurgical bleeding events and no significant increase in thromboembolic risk. The benefits of avoiding aspirin are consistent among those with prior vascular disease, including surgical or percutaneous coronary revascularization, obesity, or diabetes, which are characteristics associated with increased thrombosis risk.
Meaning: Aspirin is not required to maintain outcomes with a fully magnetically levitated LVAD in advanced heart failure, and exclusion from antithrombotic therapy is safe and associated with a reduction in bleeding events.
IMPORTANCE: Left ventricular assist devices (LVADs) enhance quality and duration of life in patients with advanced heart failure.
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.
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 at 12 months. The principal secondary end point was nonsurgical bleeding events.
RESULTS: In 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 (68%) vs those taking aspirin (74%).
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
Left ventricular assist devices (LVADs) enhance quality and duration of life in patients with advanced heart failure, irrespective of eligibility for cardiac transplant.
A fully magnetically levitated frictionless pump, engineered with wide blood flow pathways and a pulse in the pump due to fixed rotor speed changes, has demonstrated improved long-term survival by decreasing pump thrombosis and disabling strokes. Mucosal surface bleeding, particularly in the gastrointestinal system, remains burdensome as a leading cause of hospitalization and health care resource use. Patients receiving LVAD support are treated with an antithrombotic regimen that includes aspirin and vitamin K antagonist (VKA) therapy.
The role of aspirin as part of the antithrombotic regimen with VKA in patients using LVADs is controversial and has not been adequately studied. Clinical experience with different LVAD types has shown varying results.
To evaluate the role of aspirin and its clinical impact, the Antiplatelet Removal and Hemocompatibility Events With the HeartMate 3 Pump (ARIES-HM3) trial was conducted in patients with advanced heart failure with the HM3 LVAD.
Total enrollment occurred at 51 sites in North America, Europe, Kazakhstan, and Australia. All patients provided written informed consent and approval by the institutional review board or ethics committees at individual centers, and country-specific regulatory authority approval was obtained as required.
Randomized to the placebo or aspirin groups occurred in a 1:1 ratio in blocks of 4 stratified by study center. Randomization and medication management occurred through a third-party vendor. The primary end point was a composite of survival free of nonsurgical major hemocompatibility-related adverse events at 12 months, analyzed in the primary analysis population, which excluded patients with events occurring within 14 days after LVAD implantation.
In conclusion, this international, randomized, double-blind, placebo-controlled study shows that avoidance of aspirin along with the antithrombotic regimen with VKA in patients with advanced heart failure treated with a new LVAD is safe, associated with less bleeding, and does not increase thromboembolism risk.
