EDIFY: Ivabradine fails to improve outcomes in HFpEF

In individuals with HF with preserved ejection fraction, heart rate reduction with ivabradine did not improve outcomes, according to findings from EDIFY presented at Heart Failure 2017 and published in the European Journal of Heart Failure.

“[HFpEF] accounts for up to 50% of the incidence of [HF] and its prevalence is rising as a result of the aging populations,” Michel Komajda, MD, of the department of cardiology at the University of Pierre and Marie Curie Paris VI and La Pitié-Salpêtrière Hospital, Paris, and colleagues wrote in the European Journal of Heart Failure. “No treatment has yet been shown to be effective in reducing morbidity and mortality in HFpEF.”

Ivabradine (Corlanor, Amgen) is known to significantly reduce risk for CV death and hospital admission for HF in individuals with HF with reduced ejection fraction, according to the study background.

In the EDIFY study, Komajda and colleagues studied participants with HF in sinus rhythm with a heart rate of 70 bpm, N-terminal pro–B-type natriuretic peptide of 220 pg/mL and left ventricular ejection fraction of 45% (n = 179). Participants were randomly assigned to ivabradine or placebo and followed up for 8 months.

The primary endpoints were echo-Doppler E/e’ ratio, 6-minute walk test and plasma NT-proBNP concentration.

At baseline, median E/e’ was 12.8, median distance on the 6-minute walk test was 320 m, median NT-proBNP was 375 pg/mL and median heart rate was 75 bpm.

Of the 171 patients evaluated for treatment efficacy, median heart rate decreased 13 bpm after 8 months of treatment for the ivabradine group and decreased by 3.5 bpm for the control group (estimated between-group difference, –7.7 bpm; 90% CI, –10 to –5.4).

The researchers found no improvement in any of the endpoints. The median change in E/e’ was +1 for the ivabradine group and –0.6 for the control group (P = .135). The 6-minute walk test and NT-proBNP concentrations showed little difference between the treatment group and the placebo group.

There were no significant safety concerns, according to the researchers.

“Potential explanations for failure are lack of sufficient power since recruitment was interrupted due to difficulties in finding patients, and the idea that heart-rate lowering is beneficial in this condition could be wrong if patients have extensive fibrosis and, thus, no reserve in stroke volume,” Komajda said in a press release. “In that case, changes in cardiac output are totally dependent on heart rate, and reducing heart rate in this context could be detrimental.”

Although the findings were negative, “further studies may look at whether some particular phenotypes of HFpEF may benefit from [heart-rate] reduction,” the researchers concluded. – by Cassie Homer

References:

Komajda M, et al. Late-breaking trials II: Focus on chronic heart failure. Presented at: Heart Failure 2017 and the 4th World Congress on Acute Heart Failure; April 29-May 2, 2017; Paris.

Komajda M, et al. Eur J Heart Fail. 2017;doi:10.1002/ejhf.876.

Disclosure: Komajda reports receiving fees and grants from Laboratoires Servier; and honoraria, consultant fees or speakers’ bureau fees from Amgen, Bristol-Myers Squibb, Merck Sharpe & Dohme, Novartis, Novo Nordisk, Sanofi Aventis and Servier.