COAPT at 3 years: Sustained HHF reduction with mitral-valve repair over medical therapy
The efficacy of transcatheter mitral-valve repair with the MitraClip device plus guideline-directed medical therapy (GDMT) over GDMT only in reducing hospitalizations for heart failure (HHF) among patients with HF and secondary mitral regurgitation (MR) was sustained at 3 years, including in patients who crossed over from GDMT alone at 2 years, updated results of the COAPT* trial show.
“At 36 months, transcatheter mitral leaflet approximation with the MitraClip was safe, provided durable reduction in MR, reduced the rate of [HHF], and improved survival, [quality of life], and functional capacity compared to GDMT alone,” presented Dr Michael Mack, Medical Director of Cardiothoracic Surgery for Baylor Scott & White Health, Dallas, Texas, US, at TCT 2019.
Participants were 614 patients (mean age 72.2 years, 36 percent female) with HF and moderate-to-severe or severe secondary MR who were symptomatic despite maximally-tolerated GDMT. They were randomized to undergo transcatheter mitral-valve repair with the MitraClip in addition to GDMT (n=312) or GDMT only (n=302). [N Engl J Med 2018;379:2307-2318] Those in the GDMT-only arm were permitted to cross over to the device arm after 24 months; 53 patients crossed over between month 24 and 36 (median time at cross over, 25.5 months).
In the overall cohort (including crossovers), there was a significant reduction in HHF at 3 years in the MitraClip vs the GDMT-only arm (annualized rate, 35.5 percent vs 68.8 percent; hazard ratio [HR], 0.49, 95 percent confidence interval [CI], 0.37–0.63; p=0.00000006), corresponding to a number needed to treat (NNT) of 3.0 to prevent one HHF. [TCT 2019, Late-Breaking Trials 3]
The first HHF incident also occurred at a lower rate in the MitraClip vs the GDMT-only arm (46.5 percent vs 81.5 percent; HR, 0.43, 95 percent CI, 0.34–0.54; p=0.00000000000004; NNT=2.9).
All-cause mortality at 3 years was also lower in the MitraClip vs the GDMT-only arm (42.8 percent vs 55.5 percent; HR, 0.67, 95 percent CI, 0.52–0.85; p=0.001; NNT=7.9), as was a composite of all-cause mortality and HHF (58.8 percent vs 88.1 percent; HR, 0.48, 95 percent CI, 0.39–0.59; p=0.0000000000001; NNT=3.4), and the requirement of LVAD** or heart transplant (7.3 percent vs 11.4 percent; HR, 0.49, 95 percent CI, 0.25–0.94; p=0.03).
Crossover arm findings mirror that of MitraClip arm
The 1-year rate of first HHF incident among the 58*** patients who crossed over was 13.8 percent, lower than that of patients in the MitraClip and GDMT-only arms. The curve for all-cause mortality or HHF more closely mirrored that of patients who initially received the MitraClip than GDMT-only recipients.
“GDMT-only-assigned patients who crossed over and received a MitraClip experienced fewer [HHF] and deaths or [HHF] within 12 months than those who did not cross over, with rates comparable to patients originally assigned to the MitraClip,” said Mack.
Identifying the optimal patient population
In the GDMT-only arm, MitraClip (HR, 0.42; p=0.009) and beta-blocker use (HR, 0.52; p=0.006) were among factors associated with a reduced risk of first HHF at 36 months, while vasodilator use was associated with an elevated risk (HR, 2.70; p<0.0001). Similar findings were noted pertaining to risk of mortality or HHF at 36 months ie, lower risk with MitraClip (HR, 0.43; p=0.006) and beta-blocker use (HR, 0.57; p=0.01) and elevated risk with vasodilator use (HR, 1.91; p=0.0001).
“We are getting smarter at defining a responder population,” said Mack. “The responder population is patients who are maximally treated with GDMT first and … patients with … disproportionate MR. In other words, the more severe the MR, the less dilated the ventricle, the greater the chance you’re going to respond to MitraClip or other therapies,” said Mack. “There’s no question that acute procedural success and durability of the MitraClip are also predictors of [long-term success].”