MITRA-FR at 2 Years: MitraClip Still No Better Than Med Therapy

Patrice Wendling

September 03, 2019

PARIS — An additional year of follow-up in the MITRA-FR trial confirm no added benefit of percutaneous repair of functional mitral regurgitation (MR) with the MitraClip (Abbott) compared with optimal medical therapy alone.

"In the group of patients defined by the inclusion criteria of MITRA-FR, the percutaneous correction of the MR does not improve the prognosis," principal investigator Jean-François Obadia, MD, Civil Hospices of Lyon, France, said during a hotline session here at the European Society of Cardiology (ESC) 2019 Congress.

Exactly 1 year ago at the ESC congress, MITRA-FR first reported that the addition of the MitraClip to medical therapy did not decrease the rate of the composite primary end point of all-cause death and unplanned heart failure (HF) hospitalization at 1 year.

Within weeks, however, the COAPT trial reported a strikingly significant reduction in HF hospitalizations at 2 years with the MitraClip device and optimal medical therapy.

Several hypotheses have been proposed to account for the contradictory results, but "very few debates in our community have created such a controversy, with close to 200 citations of those two studies last year and no less than 17 editorials," observed Obadia.

Although some hypothesized that a MitraClip advantage would emerge with longer follow-up, the 24-month per-protocol analysis shows that rates of the composite end point did not differ significantly for the MitraClip and medical-therapy group (64.2% and 68.6%).

Secondary outcomes at 24 months with the MitraClip and medical therapy are:

  • All-cause death: 33.9% vs 35% (hazard ratio[HR], 0.99; 95% CI, 0.64 -1.52)

  • Cardiovascular death: 31.2% vs 32.1% (HR, 0.99; 95% CI, 0.63 - 1.55)

  • Unplanned HF hospitalization: 58.7% vs 63.5% (HR, 1.03; 95% CI, 0.74 - 1.43)

  • Major Adverse CV Events: 66.1% vs 68.6% (HR, 1.09; 95% CI, 0.80 - 1.48)

Results of an intention-to-treat analysis were similar, as were safety analyses, in the study, simultaneously reported in the European Journal of Heart Failure.

A Signal, Perhaps?

Although mortality remained clearly unchanged, Obadia pointed out that event curves for time to first unplanned HF hospitalization began to diverge between 12 and 24 months, showing a lower rate with percutaneous repair. The difference was even more visible in a post hoc repeat-event analysis using cumulative incidence of HF hospitalization, the main end point in COAPT, although the difference was not statistically significant at 24 months (HR, 0.87; 95% CI, 0.56 - 1.35).

"Therefore, a different benefit of percutaneous repair may be possible during the second year, even if the hazard ratio does not show any difference over the total period of 2 years," acknowledged Obadia. Nevertheless, "as an exploratory analysis of a secondary end point, the interpretation of this finding should be viewed cautiously and requires confirmation."

Reached by theheart.org | Medscape Cardiology, COAPT coprincipal investigator Gregg Stone, MD, said: "The emergence of a possible reduction in all heart failure hospitalizations in MitraClip-treated patients between 1 and 2 years is intriguing, but must be interpreted cautiously in the face of a negative trial."

Still, the overall 2-year results are confirmative of those observed in the 1-year data and provide other insights.

"An important fact that emerged was that in comparing the two trials, the 2-year mortality in the control group was 46% in COAPT vs 34% in MITRA-FR, confirming the fact that the patients in COAPT were higher risk, likely due to the greater severity of MR," Stone said. "I continue to believe that COAPT and MITRA-FR provide complementary evidence as to which patients with heart failure and secondary MR are likely to benefit, and not benefit, by the MitraClip. Patients are likely to benefit if they have truly severe secondary MR without excessive LV dilatation, and remain symptomatic despite maximally-tolerated guideline-directed medical therapy."

Speaking to theheart.org | Medscape Cardiology, Obadia said: "The populations are different, but we don't know today exactly what are the real differences between the two populations. To say that the MITRA-FR patients are too severe, it's not true: 46% of deaths after 2 years in COAPT and 34% in MITRA-FR."

He said the protocols were designed differently in the two trials and that medical treatment in the COAPT control group also must be taken into account. "If you don't treat perfectly, it's not surprising that the control group had a worse evolution." That said, Obadia also acknowledged that interpretation of the two trials is more complex than initially thought.

Mariell Jessup, MD, chief science and medical officer for the American Heart Association, said the COAPT investigators "really went out of their way" to ensure that patients were optimally medically treated, and suggested that several factors may go into why some patients don't benefit from percutaneous repair.

"It may be complicated," she told theheart.org | Medscape Cardiology. "It may require some sort of precision-medicine approach: let's look at the LV size, your maximally tolerated medical therapy, let's look at the size of your annulus, whether you have coronary disease or not, and how much regurgitation is left after the clip goes on. The surgeons have always felt very strongly that if the patient was coming out of the operating room and had significant MR, that it wasn't going to be a success. So it may be four, five factors that we don't know yet. So we're going to need a lot more individual patient data and an analysis that is going to be willing to think it may require more things."

Obadia said they will continue to follow the MIRTA-FR patients up to 5 years to see if the hospitalization trend is confirmed and that, last but not least, a patient-level meta-analysis is being planned with the COAPT team "to better understand this complex disease."

The study was supported by funding from the French Ministry of Health and Abbott Vascular. Obadia reports relationships with Delacroix-Chevalier, Edwards, Landanger, Medtronic, Abbott, and Sorin. Jessup reports no relevant conflicts of interest.

European Society of Cardiology (ESC) Congress 2019. Presentation 4200. Presented September 2, 2019.

Eur J Heart F. Published online September 2, 2019. Abstract

Follow Patrice Wendling on Twitter: @pwendl. For more from theheart.org | Medscape Cardiology, join us on Twitter and Facebook.

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