HeartMate 3 maintains superiority claim in MOMENTUM 3 final analysis
The superiority of HeartMate 3 centrifugal-flow left ventricular assist device (LVAD) over the previous-generation HeartMate II device held up to the final analysis of the MOMENTUM 3* trial, accentuated by improved survival free of disabling events in patients with advanced heart failure (HF).
At 2 years, 76.9 percent of patients on Heartmate 3 vs 64.8 of those on HeartMate II met the primary endpoint of survival free of disabling stroke or reoperation to replace or remove a malfunctioning device (relative risk [RR], 0.84, 95 percent confidence interval [CI], 0.78–0.91; p<0.001 for superiority). Pump replacement as a secondary endpoint also remained significantly lower with HeartMate 3 than with HeartMate II (2.3 percent vs 11.3 percent, RR, 0.21, 95 percent CI, 0.11-0.38; p<0.001) at 2 years. On top of that, the HeartMate 3 was associated with a lower incidence of ischaemic and haemorrhagic strokes and fewer bleeding events. [N Eng J Med 2019;doi:10.1056/NEJMoa1900486]
The number needed to treat over 2 years to avert at least 1 haemocompatibility-related adverse event (pump thrombosis, stroke, or bleed) is less than 1. “That means for every 100 patients implanted with HeartMate 3 rather than HeartMate II over a 2-year period, 108 such events are averted,” said lead investigator Dr Mandeep Mehra from the Brigham and Women’s Hospital in Boston, Massachusetts, US at ACC.19. These included 20 strokes, 22 pump thromboses, and 68 bleeds, 38 of which were gastrointestinal-related.
Two interim analyses from MOMENTUM 3 – a prespecified 6-month outcome on 294 patients and 2-year data on 366 patients – showed a lower incidence of pump thromboses and nondisabling stroke. [N Engl J Med 2017;376:440-450; N Eng J Med 2018;doi:10.1056/NEJMoa1800866] By comparison, the population in the final analysis was almost thrice larger at 1,028. Mehra described the trial as the largest, fastest-enrolling cohort of patients ever studied for LVAD.
Triad of complications addressed
“The use of LVAD in the setting of advanced HF has always been beleaguered with haemocompatibility-related complications of thrombosis, stroke, and bleeding due to the adverse reactions between the pump and circulating blood elements,” Mehra said. The new HeartMate 3, approved by US FDA in 2018 as a destination therapy for HF patients not eligible for transplant, was engineered with wide blood flow pathways to reduce shear stress and attenuate bleeds, with friction-free movement and intrinsic pulsatility to reduce stasis and avert thrombosis.
True enough, in the final results at 2 years, there was a statistically significant and meaningful reduction in GI bleeds (p<0.001) with the HeartMate 3 pump. There was also a reduction in stroke of any type and severity, thrombosis, and ventricular arrhythmias. These benefits were accompanied by fewer readmissions and days in the hospital.
“We like to highlight the survival, but there are so much more that goes into the lives of these patients more than survival,” said discussant Dr Gurusher Panjrath from the George Washington University School Medicine in Washington, DC, US in a press conference following Mehra’s presentation. “Stroke and days out of the hospital are very meaningful to patients, so is GI bleeding which has come down in the final analysis.”
New pump adding life to patients’ years
“We now have a much more forgiving pump in the LVAD space,” said Mehra. “We have really reached a point with these devices where we have added years to a patient’s life, and now, we are seeing data where we are adding life to these patients’ years because they are not suffering as much from complications such as stroke and GI bleeding.”
MOMENTUM 3 included advanced-stage heart failure patients who were candidates for an LVAD (516 for HeartMate 3 and 512 for HeartMate II) either as a bridge to transplantation or as destination therapy. Panjrath said the next move is to think how to go further with LVADs: “Can we go for a low-risk population?”
More challenges ahead
Another challenge is infection. In the trial, infections affecting the driveline exit site occurred frequently, with no differences between the two pumps. Panjrath said efforts to eliminate the driveline by developing internally powered durable pumps would be a welcome advance.
“As we start to move this information into the less-sick, more-ambulatory population, I think we need to think of more disruption in the technology that reduces the risk of infection. Perhaps that would come from using the wireless powering device where the driveline doesn’t have to exit the body. But we also are curiously noting a significant infection rate after 2 years that is beyond just the driveline, suggesting that we need to do more to understand why that is.”
The team plans to continue follow-up to another 3 years to look at long-term survival.