New research highlighted how aspirin is unnecessary in antithrombotic regimens for patients with advanced heart failure and fully magnetically levitated left ventricular assist devices (LVADs).
Among patients with advanced heart failure (HF), new research suggests that the use of aspirin is unnecessary for sustaining results when employing a fully magnetically levitated left ventricular assist device (LVAD). Keeping aspirin out of the antithrombotic regimen was also shown to not increase thromboembolism risk and was linked to a decrease in bleeding incidents.
These findings from the international, randomized, double-blind, placebo-controlled ARIES-HM3 trial were published in JAMA.
LVADs improve both the quality and length of life for individuals with advanced HF, but a significant challenge in this context is the high occurrence of nonsurgical bleeding events, which are as a primary source of morbidity. The conventional approach has been to prescribe aspirin as an antiplatelet agent alongside vitamin K antagonists (VKAs) in conjunction with continuous-flow LVADs, even though conclusive evidence regarding their effectiveness and safety is lacking. The goal of this study was to determine whether omitting aspirin from the antithrombotic regimen in patients with a fully magnetically levitated LVAD was safe and led to a reduction in bleeding incidents.
To assess this, researchers compared the effects of 100 mg per day of aspirin with a placebo, both in conjunction with VKA therapy. The study was carried out at 51 specialized centers across 9 countries, with the final analysis group including 589 patients—293 in the aspirin group and 296 in the placebo group—with a median follow-up duration of 14 months. The patient cohort was 77% male and 61% White.
The main primary end point for this study aimed to establish noninferiority of the placebo group with a –10% margin. It focused on the survival of patients without major nonsurgical hemocompatibility-related adverse events—stroke, pump thrombosis, significant bleeding, or arterial peripheral thromboembolism—that occurred more than 14 days after the LVAD implant, with a 12-month follow-up period. The primary secondary end point of the study was the occurrence of nonsurgical bleeding events.
More patients were alive and free of hemocompatibility events at 12 months in the placebo group (68%) compared with those taking aspirin (74%), and noninferiority was demonstrated (absolute between-group difference, 6.0% [lower 1-sided 97.5% CL, −1.6%]; P < .001). According to the study authors, this difference can be attributed to a lower occurrence of bleeding events in the placebo group (22.5%) than the aspirin group (28.2%).
When examining the time to the first event, fewer patients in the placebo group (36.9%) either died or experienced a significant nonsurgical hemocompatibility-related adverse event in comparison to the aspirin group (45.9%) within the 24-month period (HR, 0.73; 95% CI, 0.55-0.97; P = .03). Further, sensitivity analyses of the primary end point, including the randomized population (difference, 6.6% [lower 1-sided 97.5% CL, −1.3%]; P < .01) and the worst-case scenario (P = .02) analyses, support the primary analysis findings.
Avoiding aspirin led to a decrease in significant bleeding incidents without an elevated risk of major thrombotic events. When examining the components of thrombotic events within the primary end point, there were no notable distinctions between the study groups (RR, 0.58; 95% CI, 0.21-1.58; P = .29), and there was no difference between groups regarding ischemic and hemorrhagic strokes (RR, 0.52; 95% CI, 0.21-1.30; P = .16). Importantly, no cases of pump thrombosis were recorded.
There were also no disparities in survival rates or causes of mortality between the 2 groups. Rates of other serious adverse events also exhibited similarity in both groups.
“Importantly, this study also demonstrates that 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 historically associated with increased thrombosis risk,” the study authors said. “Hematological alterations, such as the development of acquired von Willebrand disease, may decrease thrombosis predisposition and VKA therapy may provide sufficient antithrombotic effects without the need for concomitant aspirin use.”
During the median 14 months of follow-up, a higher percentage of patients in the placebo group (71.7%) maintained a hemocompatibility score of 0 compared with the aspirin group (63.1%) (P = .03). Additionally, the rates of hospitalization due to nonsurgical bleeding were significantly lower in patients randomized to the placebo group than those in the aspirin group (13.6 vs. 23.9 events per 100 patient-years; P = .002). Notably, there was a remarkable 41% reduction in the cost of bleeding episodes, resulting in cost savings of $380,092 for the placebo group compared with the aspirin group, and patients assigned to the placebo group spent 293 (47%) fewer days in the hospital due to bleeding-related issues. Importantly, both groups experienced an improvement in their quality of life after implantation, and there were no discernible differences between the study groups.
This study has several limitations that are important to note. First, the study excluded patients with early surgical complications, those needing additional mechanical support devices with the LVAD, and those for whom aspirin was deemed necessary. However, an analysis of the randomized population, which included patients with early complications and those transitioning to open-label aspirin, supported the primary findings. Second, the majority of participants (85%) were from North America, potentially limiting generalizability to other regions, and there was underrepresentation of women with unclear reasons. Third, the study only assessed aspirin avoidance at LVAD implantation, and its effects on patients already prescribed aspirin during chronic LVAD support are uncertain. Finally, the findings may be specific to the LVAD type used and not universally applicable.
Mehra MR, Netuka I, Uriel N, et al; ARIES-HM3 Investigators. Aspirin and hemocompatibility events with a left ventricular assist device in advanced heart failure: the ARIES-HM3 randomized clinical trial. JAMA. Published online November 11, 2023. doi:10.1001/jama.2023.23204