PHILADELPHIA — Dropping aspirin from the antithrombotic regimen after HeartMate 3 left ventricular assist device (LVAD) implantation appeared safer than the usual combination approach in the ARIES-HM3 trial.
Atop warfarin or other vitamin K antagonist therapy, placebo was noninferior to low-dose aspirin for the primary composite endpoint of survival free of stroke, pump thrombosis, major nonsurgical bleeding, and arterial peripheral thromboembolism over 24 months (68% vs 74%, P<0.001 for noninferiority).
The 6.0 percentage point advantage with placebo was driven by less bleeding, with a relative 34% fewer nonsurgical bleeding events, translating to 14.5 fewer bleeding events per 100 patient-years of follow-up (P=0.002).
The already low thrombotic event risk also numerically favored the placebo group, and no device thrombosis occurred in either group, reported Mandeep R. Mehra, MD, MSc, of Brigham and Women’s Hospital Heart and Vascular Center in Boston, at the American Heart Association (AHA) annual meeting. The findings were simultaneously published in JAMA.
“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,” Mehra and colleagues concluded.
For patients who meet the trial criteria, applicability of the results can be immediate, argued an accompanying editorial by Michael Felker, MD, of the Duke Clinical Research Institute in Durham, North Carolina, and Joseph G. Rogers, MD, of the Texas Heart Institute in Houston.
“Unlike many new developments in cardiovascular therapeutics, which require initiation of novel and often expensive or complex therapies to derive clinical benefit, these data provide an opportunity to immediately improve the outcomes of patients implanted with contemporary LVADs by avoiding aspirin therapy as a new standard of care,” they wrote.
As outcomes have improved steadily with newer generations of LVADs, the antithrombotic recommendations haven’t reflected the now-lower risk of potentially catastrophic thromboembolic complications with contemporary magnetically levitated centrifugal designs, Felker and Rogers noted.
“To my knowledge, this is the first example of a medical therapy trial in patients with mechanical circulatory support that’s truly placebo [controlled] and randomized, and frankly, one of the few positive trials of medical therapy in all of Stage D heart failure,” said AHA study discussant Eric David Adler, MD, director of the Strauss-Wilson Center for Cardiomyopathy at the University of California San Diego.
He called attention to the 47% reduction in hospital days without aspirin in the trial. “We can all agree there are very few good days spent in hospital for our patients. And so by reducing the hospitalization days by 47%, we’re dramatically changing this therapy.”
He predicted that lowering bleeding risk could increase the utility of LVADs overall and increase uptake.
Adler related a conversation with Mehra the night before the presentations: “One of the takeaway points for me is he said, ‘We have to stop calling it baby aspirin. … We should call it monster aspirin.’ I don’t know about that, but I think we can all do away with this adjective, which suggests it’s something benign.”
The trial randomized 628 patients with advanced heart failure who received a HeartMate 3 LVAD to double-blind treatment with either aspirin (100 mg daily) or matching placebo along with their vitamin K antagonist (target international normalized ratio of 2.0-3.0). There was no difference in time in therapeutic range between groups.
Of the participants, 77% were men, 61% were white, and 29% were Black. The U.S. and Canada accounted for 85% of enrollment, while the rest accrued from the Czech Republic, Austria, Italy, France, U.K., Kazakhstan, and Australia.
Subgroup analyses did not suggest heterogeneity, “including in patients who would typically be considered to have another indication for aspirin therapy, such as patients with prior coronary artery bypass grafting (11%), prior percutaneous coronary intervention (25%), and prior stroke (13%),” the editorialists noted. “However, given the modest sample size of these groups, it is important to point out that CIs for these subgroups were wide, and the point estimates for both patients with prior coronary artery bypass grafting and prior percutaneous coronary intervention slightly favored the aspirin group.”
The researchers also cautioned against extrapolation to other LVAD devices, which the editorialists noted carry different risk of thromboembolic complications and, thus, different balance of risks and benefits.
In the trial, thrombotic event components of the primary endpoint came out similar between the study groups (RR 0.58, 95% CI 0.21-1.58), nor was there a difference in ischemic and hemorrhagic stroke specifically (RR 0.52, 95% CI 0.21-1.30). Mortality did not differ between groups.
A key question now is what to do about aspirin in patients with other traditional indications for aspirin therapy, such as prior coronary artery bypass grafting and percutaneous coronary intervention, the editorialists noted. Whether LVAD patients doing well on aspirin therapy should have it discontinued and what to do about those with prior thromboembolic complications from their LVAD need further study for more definitive answers, Felker and Rogers added.
The trial was funded by Abbott.
Mehra disclosed consulting fees paid to his institution from Abbott during the trial and personal fees from Moderna, Natera, Transmedics, Paragonix, NuPulseCV, FineHeart, and Leviticus.
Felker disclosed personal fees from Abbott, Novartis, Cytokinetics, Innolife, Boehringer-Ingelheim, Regeneron, Myovant, Sequana, Windtree, Rocket, WhiteSwell, VWave, and LivaNova and grants from Bayer, BMS, Novartis, Merck, Medtronic, and CSL-Behring. Rogers disclosed no relationships with industry.
Source Reference: Mehra MR, et al “Aspirin and hemocompatibility events with a left ventricular assist device in advanced heart failure: The ARIES-HM3 randomized clinical trial” JAMA 2023; DOI: 10.1001/jama.2023.23204.
Source Reference: Felker GM and Rogers JG “Addition by subtraction in mechanical cardiac support” JAMA 2023; DOI: 10.1001/jama.2023.22490.