Aspirin may not be needed in patients with fully magnetically levitated LVAD
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Key takeaways:
- In patients with advanced HF on a LVAD, removing aspirin from the antithrombotic regimen was safe.
- Avoiding aspirin reduced bleeding and did not raise risk for thrombotic events or stroke.
PHILADELPHIA — In patients with advanced HF and a fully magnetically levitated left ventricular assist device, avoiding aspirin was safe and reduced bleeding, researchers reported at the American Heart Association Scientific Sessions.
The ARIES-HM3 trial included 628 patients with advanced HF implanted with the fully magnetically levitated LVAD (HeartMate 3, Abbott) and taking a vitamin K antagonist who were randomly assigned to receive aspirin or placebo.
The HeartMate 3 significantly improved the incidence of pump thrombosis and stroke compared with earlier-generation LVADs, but not nonsurgical bleeding, so it made sense to pursue a trial of medical therapy in the LVAD population, which had never been done before, to determine whether change in medical therapy could improve bleeding, Mandeep R. Mehra, MBBS, MSc, medical director of the Heart and Vascular Center and professor of medicine and William Harvey Distinguished Chair in Advanced Cardiovascular Medicine at Brigham and Women’s Hospital and Harvard Medical School, told Healio.
A vitamin K antagonist plus aspirin has been the standard medical therapy in this population for 40 years, Mehra said in an interview.
“Bleeding is one of the top three reasons for rehospitalization of patients with LVADs,” Mehra told Healio. “Traditionally, we have always focused on testing a device vs. a device in this space. Now we only have one device in this space — the others have become legacy devices — so we had no other option but to start moving our attention to background medical therapy.” It was easier to design a trial around dropping aspirin than one around dropping a vitamin K antagonist, he said, noting that ARIES-HM3 is the first international trial of any kind related to LVADs.
The results were simultaneously published in JAMA.
Of the 589 patients able to be included in the primary analysis, the mean age was 58 years (median, 60 years), 77% were men and one-third were Black. The primary endpoint was survival free from major nonsurgical (> 14 days after implant) hemocompatibility-related adverse events — including stroke, pump thrombosis, major bleeding or arterial peripheral thromboembolism — at 1 year.
Compared with the aspirin group, the placebo group had more patients achieve the primary endpoint (74.2% vs. 68.1%; absolute between-group difference, 6 percentage point improvement in event-free survival with placebo; lower 1-sided 97.5% CI, 1.6%; P for noninferiority < .001), according to the researchers. A time-to-first-event analysis favored placebo at 2 years (HR = 0.73; 95% CI, 0.55-0.97; P = .03), Mehra said.
The placebo group had reduced risk for nonsurgical bleeding events compared with the aspirin group (RR = 0.66; 95% CI, 0.51-0.85; P = .002). Mehra said during the presentation that moderate bleeding, severe bleeding and gastrointestinal bleeding all favored the placebo group.
The researchers reported no differences between the groups in thrombotic events (RR = 0.58; 95% CI, 0.21-1.58), stroke (RR = 0.52; 95% CI, 0.21-1.3) or mortality (HR = 0.9; 95% CI, 0.5-1.62; P = .71) at 2 years, according to the researchers.
“The results were surprising,” particularly the nonsurgical bleeding events outcome, Mehra told Healio. “We thought that at the most we would show safety of pulling out aspirin, so we constructed the trial based on noninferiority. All we wanted to show was that we did not need aspirin. Then we can see if there were a little more strokes and what subgroups those might be in. Not only did we meet noninferiority easily, but we showed evidence of a marked reduction in bleeding — a 34% reduction in bleeding of any cause and a 39% reduction in gastrointestinal bleeding.”
Time in therapeutic range for vitamin K antagonists did not differ between the groups (P = .93), Mehra said during the presentation.
The results were consistent across subgroups, but the benefit of placebo was more pronounced in patients with a history of bleeding compared with those with no history (P for interaction < .01), he said.
Aspirin avoidance was associated with a 47% reduction in days hospitalized due to bleeding events and a 41% reduction in cost of bleeding hospitalization, he said.
“The trial is convincing because we powered it with greater than 90% power to say that it is safe to remove aspirin,” Mehra told Healio. “Also, we showed generalizability across all the subgroups and we had biochemical evidence that the finding was because of aspirin. Aspirin, even in low doses, was having a significant therapeutic effect. This trial shows the community that we need to beat placebo first before we start introducing treatments.”
Reference:
Perspective
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This was an important trial for the HeartMate 3 patient population. The endpoints showed that we probably don’t need aspirin. While it is tempting to call for all of these patients to get off of aspirin, it is important to note that this study started from the beginning, in patients newly implanted with an LVAD. It does not necessarily apply to people who have already been on anticoagulation with aspirin and warfarin who have not had any problems. Whether it gets extrapolated to that population will be patient- and clinician-dependent.
The three biggest problems for patients with LVADs are infections starting with the driveline, thromboembolic complications and bleeding. We do everything we can to minimize the risk for bleeding, including, in rare cases, taking a patient off the vitamin K antagonist. But it is a chronic problem.
We now need to investigate what happens if we remove aspirin in stable patients who were implanted some time ago and have had long-term support with no bleeding complications.
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Mehra MR, et al. LBS.03. Heart failure - VADS, kids, and money. Presented at: American Heart Association Scientific Sessions; Nov. 11-13, 2023; Philadelphia.
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