The FDA’s Circulatory Systems Devices Advisory Panel determined Dec. 7 in a three-to-two vote that the overall clinical benefits of Medtronic's cardiac resynchronization therapy with implantable cardioverter-defibrillator (CRT-D) devices outweigh the risks in treating certain mildly symptomatic heart failure (HF) patients. The recommendation, which was based on data from the RAFT and REVERSE trials, could pave the way for a potential expanded labeling approval for these devices, if the FDA chooses to accept the panel’s decision.
While CRT-Ds are currently approved for patients with moderate-to-severe HF, the RAFT and REVERSE studies showed their use can benefit mildly symptomatic HF patients by reducing mortality and HF hospitalization rates.
Specifically, the panel voted in favor of the CRT-D devices’ strong safety (yes: five votes, no: 0 votes) and efficacy (yes: three votes, no: two votes) profile in treating a mildly symptomatic patient population. The panel voted in favor of the overall risk-benefit profile (yes: three votes and no: two votes).
The FDA will consider the panel’s feedback as it reviews Medtronic’s request to expand its CRT-D indication to include NYHA Class II HF patients with a left ventricular ejection fraction of less than or equal to 30 percent, left bundle branch block, and a QRS duration greater than or equal to 120 ms.
Findings from RAFT (Resynchronization/Defibrillation in Ambulatory Heart Failure Trial), which was originally presented at AHA.10 and later published in the New England Journal of Medicine, showed that CRT-D significantly reduced mortality for mildly symptomatic HF patients (NYHA Class II) by 29 percent when compared with patients treated with guideline-recommended implantable ICDs and medical therapy. The CRT-D group also has a 25 percent reduction in the rates of death and hospitalization for patients with Class II or III HF, a wide QRS complex and left ventricular systolic dysfunction.
With 610 patients studied, REVERSE (REsynchronization reVErses Remodeling in Systolic left vEntricular dysfunction) was a global, randomized, double-blind trial that demonstrated the impact of CRT in mild HF patients or asymptomatic patients who previously had HF symptoms.
Minneapolis-based Medtronic, which issued a statement on the advisory panel’s ruling, said that the use of Medtronic CRT-D devices for mildly symptomatic HF patients (NYHA Class II) is investigational and not an approved use in the U.S.