FDA Advisors Mostly Positive on Expanding CRT-D Indications

Shelley Wood

December 08, 2011

December 8, 2011 (Gaithersburg, Maryland) — Indications for cardiac resynchronization therapy defibrillators (CRT-Ds) could be widened to include symptomatic NYHA class 2 patients who meet additional criteria, most of a five-member FDA advisory committee told the FDA yesterday.

The expanded indications sought by the sponsor, Medtronic, include patients with NYHA functional class 2 HF who remain symptomatic despite stable, optimal medical therapy and who have left bundle branch block with a QRS duration >120 ms and a left ventricular ejection fraction (LVEF) <30%.

Medtronic's line of CRT-D devices was first approved in June 2002 for patients with class 3–4 HF, an LVEF <35%, and a QRS duration of >130 ms. As previously reported by heartwire , those indications were later altered to include simply "prolonged QRS duration."

Over the long day's discussion, panel members struggled with the data backing up the proposed indication, drawn from a subset of patients from two trials. Support for the efficacy of CRT-D in patients with less severe LV dysfunction comes from both the Resynchronization Reverses Remodeling in Systolic Left Ventricular Dysfunction (REVERSE) and the Resynchronization/Defibrillation for Ambulatory Heart Failure (RAFT) studies, both previously reported by heartwire . But as briefing documents provided by the FDA prior to today's meeting pointed out, both REVERSE and RAFT included an even wider range of patients than those targeted by today's request for an indication expansion.

Ultimately, on the question of whether Medtronic CRT-Ds are safe for use in patients who meet the criteria specified in the proposed indication, the panel unanimously voted yes. On a second question, addressing efficacy in this group, the vote was split, with three yes votes and two no votes, identical to the vote for the third and final question, which asked whether the benefits in this population exceeded any risks.

Dr Ralph Brindis (Oakland Kaiser Medical Center, CA), who voted yes for all three questions, noted that it was difficult for the panel to make decisions based on subset data. But with the totality of information, he said, "I felt quite comfortable with voting yes on all three issues, and I will congratulate the sponsor and the FDA for thinking about doing postapproval work so we can further home in and define the treatment benefits in these patients and understand our practice patterns going forward."

The two panel members who voted no on the last two questions, Dr Richard Lange (University of Texas, San Antonio) and Dr Michael Ferguson (National Naval Medical Center, Bethesda, MD), both said their only quibble was in the QRS cutoff of >120 ms proposed by the sponsor.

"Had the criteria been >150 ms, it would have been a yes vote [from me]," Lange said. And Ferguson added, "I completely agree. I don't think we determined optimal QRS duration. I think we should study that in some other capacity."