European Journal of Heart Failure | 2019
A tale of two trials; chapter 2
Abstract
Last year witnessed the simultaneous publication of two randomized trials attempting to determine the benefits (if any) of the correction of moderate to severe or severe secondary (functional) mitral regurgitation (MR) with the MitraClip device (Abbott Inc, Santa Clara, CA, USA) in addition to guideline-directed medical therapy (GDMT) in patients with heart failure (HF). One trial, the COAPT trial, was unequivocally positive demonstrating clear benefit in the primary effectiveness endpoint of all HF hospitalizations within 24 months.1 Also demonstrated in this trial was a mortality benefit and the trial met all 10 of the pre-specified and powered secondary endpoints. However, the other trial, MITRA-FR, conducted in approximately the same time frame in a similar study cohort of patients, found a diametrically opposite result with no demonstrable benefit in the primary effectiveness endpoint of death and HF hospitalization at 12 months.2 These discordant outcomes obtained using the same device to treat the same disease at roughly the same time has led to much debate and conjecture as how to explain these seemingly irreconcilable differences. A number of possible explanations have been proposed including the use of different primary endpoints (all HF hospitalizations vs. death and HF hospitalizations), different number of subjects enrolled (614 vs. 304) and longer duration of follow-up (24 vs. 12 months) in COAPT vs. MITRA-FR, respectively. In addition, patients treated in the COAPT trial had better acute procedural success and greater durability defined as less recurrence of MR. Other plausible explanations for the discordance in outcomes include less severe grades of MR included in MITRA-FR based upon different echocardiographic definitions of severity of secondary MR in the European and the American guidelines which were used in the trial and greater degrees of left ventricular (LV) dilatation in MITRA-FR.3,4 Furthermore, COAPT required detailed documentation of maximally tolerated medication doses over 3 months prior to entry into the trial, which had to be adjudicated on a conference call by a committee of HF specialists. In contrast, titration of GDMT was allowed after randomization in MITRA-FR