WASHINGTON – Early treatment with cardiac-resynchronization therapy with a defibrillator showed a significant survival benefit in patients with mild heart failure, left ventricular dysfunction, and left bundle-branch block, but no benefit was seen among those who did not have bundle-branch block.
In this long-term follow-up analysis of the MADIT-CRT trial, there was a trend toward increased all-cause mortality among those who did not have left bundle-branch block, said Dr. Ilan Goldenberg of the Israeli Association for Cardiovascular Trials and Tel Aviv (Israel) University at the annual meeting of the American College of Cardiology. MADIT-CRT (Multicenter Automatic Defibrillator Implantation Trial – Cardiac Resynchronization Therapy) followed 1,692 surviving patients for a median of 5.6 years, as the first phase, and 854 patients enrolled in registries in the United States and elsewhere, as the second phase, and the data were merged. The primary endpoint was death from any cause.
The results indicate that in patients with mild heart failure (HF) symptoms, left ventricular dysfunction, and left bundle-branch block (LBBB), "early intervention with cardiac resynchronization therapy is associated with a significant long-term survival benefit, whereas currently, there is no evidence for any clinical benefit associated with cardiac resynchronization therapy in mild heart failure patients" without LBBB, he concluded.
In the original study, treatment with a cardiac resynchronization therapy–defibrillator (CRT-D) was associated with a significant 34% reduction in the risk of nonfatal HF events or all-cause mortality over a median 2.4 years follow-up. But the effect of the device on risk of all-cause mortality was neutral, possibly because of the short-term follow-up, so whether treatment could affect long-term survival in this population was unclear, he pointed out. Benefit in the original trial appeared to be restricted to patients with LBBB, he added.
In the long-term study, 7 years after enrollment, cumulative all-cause mortality in those with LBBB was 18% among those patients treated with CRT-D, compared with 29% among those who received defibrillator therapy alone, a statistically significant difference that represented a 41% reduced risk. The separation in event rates appeared after 1 year and continued for 7 years. Based on this difference in survival, nine patients would need to be treated with CRT-D to save one life over 7 years, Dr. Goldenberg said. The survival benefit was present regardless of age, sex, HF functional class I or II, baseline ejection fractions or cardiac volume, or QRS duration.
In patients with LBBB, treatment was also associated with a "pronounced" risk reduction of 62% in heart failure events, with benefits that started to appear after enrollment and continued through follow-up, and a significant 55% reduction in the combined endpoint of heart failure and death.
"In contrast, among patients without LBBB, we see that even after multivariate adjustment, there was no evidence for any clinical benefit associated with cardiac resynchronization therapy, with even a trend to a 57% increased risk of all-cause mortality" in patients without LBBB. In contrast, in patients who did not have left bundle-branch block, "there was no evidence for any clinical benefit associated with cardiac resynchronization therapy during long-term follow-up," for all-cause mortality and for nonfatal HF events, Dr. Goldenberg said.
The earlier results were published in 2009 (N. Engl. J. Med. 2009;361:1329-38).
The current study was published simultaneously with its presentation in the New England Journal of Medicine (2014, March 30 [doi:10.1056/NEJMoa1401426]).
The study was funded by unrestricted research grants from Boston Scientific to the University of Rochester, N.Y., and the Israeli Association for Cardiovascular Trials. Dr. Goldenberg disclosed having received grant support from Boston Scientific outside of this study.