The End of the Aspirin Era in Left Ventricular Assist Devices

Despite contemporary treatments for heart failure, a significant number of patients reach the end-stage of this disease every year. Patients with end-stage heart failure have a very poor prognosis, with 1 year mortality rates that exceed 90%. The only hope for these patients is life-prolonging therapy with either a heart transplant or a durable left-ventricular assist device implantation.

While the original left ventricular assist devices (LVADs) were unreliable and only extended life a few years, the current devices offer excellent short-term and medium-term outcomes. While the risk of complications is substantially reduced with contemporary LVADs, many patients will still experience issues with bleeding and clotting (ie, hemocompatibility-related adverse events [HRAE]).

The standard thromboprophylatic regimen for durable LVADs is the combination of aspirin and warfarin. This regimen was chosen arbitrarily by the initial designers of LVAD technology, and it was never tested in a randomized fashion. In this week’s issue of Talking Therapeutics, we evaluate the first trial to do so.

Talking Point: Aspirin is Not Needed

The ARIES-HM3 trial randomized more than 600 patients to aspirin (100 mg/d) vs placebo with vitamin-K antagonist therapy across 51 centers in 9 countries. 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 (including stroke, pump thrombosis, major bleeding, or arterial peripheral thromboembolism) at 12 months.

More patients were alive and free of hemocompatibility events at 12 months in the placebo group (68%) vs those taking aspirin (74%). Aspirin avoidance was associated with reduced nonsurgical bleeding events (relative risk, 0.66 [95% confidence limit, 0.51-0.85]; P=.002) with no increase in stroke or other thromboembolic events. Multiple different subgroup analysis failed to identify a patient subtype who benefited from aspirin therapy.

Talking Point: The End of an Era

The inclusion of aspirin with a vitamin-K antagonist was completed empiric and was likely based on favorable data from mechanical prosthetic heart valves. The original LVADs operated using pulsatile flow, but once the technology evolved to continuous flow, the risk of mucosal hemorrhage drastically increased.

In order to mitigate this risk, clinicians start to omit aspirin from their thromboprophylactic regimens. After publication of several positive case series, the ARIES-HM3 trial was designed to rigorously test the hypothesis that aspirin could be safely dropped.

With these results now published, we can safely transition contemporary LVAD recipients to monotherapy with a vitamin-k antagonist.