The expanded indication includes New York Heart Association (NYHA) Class II heart failure patients with a left ventricular ejection fraction (LVEF) of less than or equal to 30%, left bundle branch block (LBBB), and a QRS duration greater than or equal to 130 milliseconds. Nearly 200,000 Americans are considered NYHA Class II, with another 620,000 people worldwide fitting this designation. Medtronic CRT-D devices were previously indicated to treat certain patients with moderate-to-severe heart failure (NYHA Class III and IV), and have safely and effectively been used in these patients for more than a decade.
The FDA’s decision for the expanded indication rests on data from the pivotal REVERSE (Resynchronization reverses remodeling in systolic left ventricular dysfunction) and landmark RAFT (Resynchronization/defibrillation in ambulatory heart failure trial) clinical trials, which showed that CRT-D can benefit mildly symptomatic heart failure patients by reducing mortality and heart failure hospitalisation rates.
“The RAFT and REVERSE study findings provide strong clinical evidence validating the safety, efficacy and lifesaving benefits of CRT-D for treating systolic heart failure patients with milder symptoms,” said Michael R Gold, REVERSE study investigator and steering committee member, Michael E Assay professor of medicine and director of cardiology at the Medical University of South Carolina, USA. “This expanded indication fulfills an unmet need by treating these patients in the earlier stages of heart failure, before their symptoms more significantly impact their quality of life.”
While certain NYHA Class II patients are already indicated for an implantable cardioverter defibrillator (ICD) to protect them from sudden cardiac arrest, they are still vulnerable to experiencing an exacerbation of their heart failure. In fact, sudden cardiac arrest is responsible for more than 60% of deaths among patients with mild-to-moderate heart failure. However, a growing body of clinical research suggests that earlier intervention with CRT-D can decrease the risk of morbidity and mortality in this mildly symptomatic patient population.
About the RAFT trial
Findings from the landmark RAFT clinical trial, published in the New England Journal of Medicine, showed that CRT-D significantly reduced mortality for mildly symptomatic heart failure patients (NYHA Class II) by 29% when compared to patients treated with guideline-recommended implantable ICDs and medical therapy (p=0.006; HR=0.71). The study also demonstrated a significant reduction (27 percent) in combined mortality and heart failure hospitalisations for this population (p=0.001; HR=0.73), consistent with previously published studies. All patients were followed for at least 18 months, and had an average follow-up of 40 months, making it the longest follow-up and largest patient months-of-experience of any study of CRT therapy.
About the REVERSE trial
With 610 patients studied, REVERSE was the first large-scale, global, randomised, double-blind trial to demonstrate the impact of CRT in mild heart failure patients or asymptomatic patients who previously had heart failure symptoms. All randomised subjects received a score of improved, unchanged or worsened, utilising the Clinical Composite Response. For the pre-specified primary endpoint, the results showed that 21% of subjects without CRT worsened, compared to 16% with CRT (p=0.10); however, post-hoc analyses demonstrated that collectively comparing all the classifications of improved, unchanged or worsened was significant (p=0.004).
Importantly, more patients in the trial improved with CRT than without (54% vs. 40%, respectively). Additionally, the analysis of pre-specified secondary endpoints in the REVERSE trial showed that CRT leads to improvement in both cardiac structure and function as measured by echocardiography, meaning the heart size improves and beats more effectively. CRT also delayed the time to first heart failure hospitalisation in this patient group and reduced heart failure hospitalisation or all cause death by 51% (p=0.004, post-hoc).