PracticeUpdate Cardiology Best of 2018

ESC 2018 23

Percutaneous Reduction of SecondaryMitral Regurgitation in Heart Failure Appears Futile

to more than 10% of those older than age 70 years. 1 In secondary mitral regurgitation of the advanced stages of heart failure, the mitral valve is structurally normal but does not work properly due to a dilated left ventricle. Though associated with a worse progno- sis, reducing secondary mitral regurgitation has not been shown to improve survival. Results of the Cardiovascular Outcomes Assessment of the MitraClip Percutaneous Therapy for Heart Failure Patients with Func- tional Mitral Regurgitation (COAPT) study, including more than 600 patients with mitral regurgitation and systolic heart failure, are expected in September 2018. The outcome should help clarify the use of this procedure. The objective of COAPT is to confirm the safety and effectiveness of the MitraClip device for moderate-to-severe or severe functional mitral regurgitation in patients with symptomatic heart failure who are treated per standard of care and who have been determined to not be candidates for mitral valve surgery. COAPT will provide the opportunity to strengthen or add labeling claims regard- ing safety and clinical benefits of the MitraClip device for patients with sympto- matic heart failure with moderate-to-severe or severe functional mitral regurgitation. Subjects will be enrolled at up to 100 inves- tigational sites. Approximately 305 subjects are targeted to receive the study device. As part of COAPT, a subset of patients are registered in the cardiopulmonary exercise substudy. Its objective is to evaluate exer- cise responses in a subcohort of subjects who receive the MitraClip device vs the control group. The latter do not receive MitraClip device. Subjects in the substudy will contribute to analyses of COAPT pri- mary and secondary endpoints. An extension of COAPT, the COAPT contin- ued access study is evaluating the MitraClip device for clinically significant functional mitral regurgitation in patients with symp- tomatic heart failure who are treated per standard of care and who have been deter- mined not to be candidates for mitral valve surgery. Completion of this study is antici- pated in 2024. Reference 1. Ponikowski P, Voors AA, Anker SD, et al. 2016 ESC guidelines for the diagnosis and treatment of acute and chronic heart failure. Rev Esp Cardiol (Engl Ed) . 2016;69(12):1167. www.practiceupdate.com/c/72632

Percutaneous mitral valve repair does not improve survival or symptoms, nor does it reduce heart failure hospitalizations vs standard medical treatment alone. P ercutaneous reduction of secondary mitral regurgitation appears futile in patients with heart failure.

failure and secondary mitral regurgitation.” He continued, “The reduction in mitral regurgitation that was achieved with the intervention did not translate into a clinical benefit in patients with heart failure. There is therefore no reason to perform this pro- cedure in all patients with heart failure and secondary mitral regurgitation. Other rand- omized trials could examine whether there are subgroups that might be more suitable candidates.” MITRA.FR was designed to determine whether this procedure could reduce the rate of all-cause death or unscheduled hos- pitalization for heart failure over 12 months vs optimal medical treatment alone. A total of 304 patientswith symptomatic heart failure, poor left ventricular function (left ven- tricular ejection fraction 15–40%), and severe secondary mitral regurgitation were enrolled from37 hospitals in France. Patients received optimal medical treatment with an angio- tensin-converting enzyme inhibitor (if not tolerated, an angiotensin receptor blocker was substituted), beta-blocker, mineralocor- ticoid receptor antagonist, and diuretic. Patients were then randomized to percuta- neous mitral valve repair or no intervention (control group). Patients were followed for 12 months. More than 90% of procedures were per- formed successfully with no significant safety concerns. Mitral regurgitation was reduced substantially in patients who underwent the procedure compared with those who received medical therapy alone. Nevertheless, no statistically significant difference was observed in the primary endpoint of death and unscheduled heart failure rehospitalization at 12 months. The latter occurred in 55% of patients receiving the intervention and 52% of those treated with medical therapy alone. The 2017 European guidelines state that percutaneous edge-to-edge repair may be considered in patients with secondary mitral regurgitation and heart failure consid- ered at high risk of open heart surgery. The intervention involves inserting one or more clips through the femoral vein then attach- ing the two mitral valve leaflets together so that they close more effectively. As published in 2016 by Ponikowski et al, approximately 2% of adults in developed countries suffer from heart failure, rising

This outcome of the Multicentre Study of Percutaneous Mitral Valve Repair MitraClip Device in Patients with Severe Second- ary Mitral Regurgitation (MITRA.FR) was reported at ESC 2018. In an ESC press release, Jean-Francois Obadia, MD, of Civil Hospices of Lyon, France, said, “We show for the first time that despite reducing secondary mitral regurgitation, percutaneous repair of the mitral valve does not improve survival or symptoms, or reduce heart failure hospi- talizations compared to standard medical treatment alone. This strongly suggests that this procedure is futile in patients with heart strokes and deaths. After the trial, patients continued to receive routine care. A second aim of the ASCOT was to discover whether a statin would pro- vide added protection against coronary heart disease in patients with high blood pressure and cholesterol levels below 6.5 mmol/L. Patients with a blood cholesterol level of ≤6.5 mmol/L were randomized to atorvastatin or placebo for 3.3 years when the trial was stopped prematurely because atorvastatin prevented more cardiovascular events. Patients were offered atorvastatin for the remainder of the antihypertensive arm of the trial. During this 2.2-year period, approximately two-thirds of patients who had been assigned to either atorvastatin or placebo took atorvastatin. A third aim of ASCOT was to evaluate the newer vs older antihypertensive treat- ment in patients with high blood pressure and high cholesterol (>6.5 mmol/L). These patients did not participate in the randomized lipid-lowering arm of the trial, and all received a statin for 5.5 years. Mark Caulfield, FMedSci, who is Director of the William Harvey Research Institute and did not participate in ASCOT Legacy, said, “This study confirms the importance of low- ering blood pressure and cholesterol to prevent disabling and life-shortening car- diovascular disease.” www.practiceupdate.com/c/72631

VOL. 3 • NO. 4 • 2018