AHA: RAFT suggests widening ICD-CRT indications for lesser HF
CHICAGO—Adding cardiac resynchronization therapy (CRT) to an implantable cardioverter-defibrillator (ICD) reduce rates of death and hospitalization by 25 percent for patients with class II or III heart failure, a wide QRS complex and left ventricular systolic dysfunction, based on the results of the late-breaking RAFT study presented today at the American Heart Association (AHA) Scientific Sessions.

RAFT (Resynchronization/defibrillation for Ambulatory heart-Failure Trial) is a multicenter randomization trial, which followed 1,798 patients for a mean of 40 months.

Patients with N.Y. Heart Association class II or III heart failure, a QRS duration of 120 msec or more, and a left ventricular ejection fraction of 30 percent or less were randomly assigned to receive either an ICD or an ICD plus CRT; both groups also received optimal medical therapy. On average, all patients were followed for more than 3 years.

The primary outcome occurred in 33.2 percent of the patients in the ICD–CRT group and 40.3 percent of patients in the ICD group, reported principal investigator Anthony S.L. Tang, MD, from the Island Medical Program, University of British Columbia in Vancouver. In the ICD–CRT group, 186 patients died, as compared with 236 in the ICD group, and 174 patients were hospitalized for heart failure, as compared with 236 in the ICD group.

However, at 30 days after device implantation, the investigators found the adverse events had occurred in 124 patients in the ICD-CRT group, as compared with 58 in the ICD group.

Tang said that the all-cause mortality with an absolute reduction of 6 percent over a treatment period of five years, and 14 patients would need to be treated for five years to prevent one death. Also, 11 patients would need to be treated for five years to prevent one hospitalization for heart failure.

However, in an accompanying editorial in the New England Journal of Medicine, where the study was published simultaneous to this morning’s presentation, Arthur J. Moss, MD, from the University of Rochester School of Medicine in Rochester, N.Y., wrote, “It is interesting that improved survival did not become evident until about two years after the initiation of therapy in the ICD–CRT group, which suggests that the reduction in heart-failure events preceded the diminution in mortality.”

Moss also asked three questions, which he suspects will be answered by upcoming secondary studies:
  • Does CRT prevent or reduce recurrent heart failure?
  • Does CRT inhibit ventricular tachycardia and ventricular fibrillation?
  • Since there are many subdivisions of the coronary veins, does the branch of the coronary vein in which the left ventricular pacing lead is located influence the efficacy of CRT?

He concluded that “recent findings documenting the use of CRT in preventing heart failure in minimally symptomatic patients are indeed breathtaking.”

As a discussant to RAFT this morning at the AHA conference, Clyde W. Yancy, MD, medical director at Baylor Heart and Vascular Institute in Dallas, took Moss’ comments one step further. “While we previously had a dearth of positive information or significant clinical data, these data, along with several other recent trials, give us a reason for renewed enthusiasm about heart failure,” he said.

Examining MADIT-CRT and REVERSE along with the findings of RAFT, Yancy pointed out some “consistency in [patient] response, in addition to some important differences.” The differences include different HF classes, based on left ventricular ejection fraction; QRS duration; endpoints; and outcomes.

“Despite these differences, it is significant to see the consistency of response that ICD added to CRT in patients with mild to moderate HF is beneficial,” Yancy said. “Therefore, it is clearly evident that CRT-ICD works well in this patient population, and we will need to incorporate these findings into clinical practice.”

Yancy called for an expansion of the indications from those patients with class III or IV HF to those patients with a lesser degree of HF. “Importantly, we should anticipate clinical practice to change,” but he also cautioned that the cost-effectiveness data has not yet been released for RAFT.

Both Tang and Yancy commented on the subgroup analysis in RAFT, the results of which are not definitive, but female patients and those with a left bundle branch block pattern, appear to reap the greatest benefits from the combination of ICD and CRT.

The Canadian Institutes of Health Research and Medtronic of Canada provided financial support for the RAFT trial.