Ivabradine in Heart Failure With Preserved Ejection Fraction

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Three deaths were reported in the ivabradine group, but they were determined to be unrelated to treatment.
Three deaths were reported in the ivabradine group, but they were determined to be unrelated to treatment.

Lowering heart rate with ivabradine did not improve exercise capacity or diastolic function in patients with heart failure with preserved ejection fraction (HFpEF), according to the Preserved Left Ventricular Ejection Fraction Chronic Heart Failure With Ivabradine Study (EDIFY) trial results published in the European Journal of Heart Failure.

Half of all new heart failure cases are patients with HFpEF, the prevalence of which is increasing. Having a high heart rate is a risk factor for morbidity and mortality in HFpEF and other types of heart failure. However, there are currently no treatments for HFpEF that reduce the risk for poor outcomes and death.

Ivabradine lowers heart rate via selective blockade of the If current, and its use is associated with a decreased risk for hospital admission, worsening heart failure, and cardiovascular death in patients with heart failure with reduced ejection fraction.

In the EDIFY proof-of-concept trial, investigators evaluated whether ivabradine improved exercise capacity and diastolic function and lowered N-terminal pro B-type natriuretic peptide (NT-proBNP) levels in patients with HFpEF.

A total of 179 patients were randomly assigned to treatment with ivabradine or placebo twice a day for 8 months, and 171 were included in the efficacy analysis. Patient characteristics included New York Heart Association (NYHA) classes II and III, heart rate ≥70 bpm, sinus rhythm, left ventricular EF ≥45%, and NT-proBNP of ≥220 pg/mL (BNP ≥80 pg/mL).

Ivabradine reduced heart rate to a greater extent than placebo (−13.0 bpm vs −3.5 bpm; 90% CI, −10 to −5.4; P <.0001).

However, compared with placebo, ivabradine did not improve diastolic function or exercise capacity, which were measured using echo-Doppler E/e′ ratio (+1.0 vs −0.6; 90% CI, 0.3-2.5; P =.135) and the 6-minute walking test (6MWT; 0.0 m vs +11.0 m; 90% CI, −19.1 to 11.6; P =.882), respectively. There was also no difference between the groups in change in NT-proBNP levels.

Rates of adverse events, including episodes of atrial fibrillation, were similar between the ivabradine and placebo groups. Although 3 deaths occurred in the ivabradine group, they were not considered to be related to treatment.

"These findings do not support the use of ivabradine in this group of patients with HFpEF. Further studies may look at whether some particular phenotypes of HFpEF may benefit from [heart rate] reduction," the researchers concluded.

Reference

Komajda M, Isnard R, Cohen-Solal A, et al; Preserved Left Ventricular Ejection Fraction Chronic Heart Failure With Ivabradine Study (EDIFY) Investigators. Effect of ivabradine in patients with heart failure with preserved ejection fraction: the EDIFY randomized placebo-controlled trial [published online April 30, 2017]. Eur J Heart Fail. doi:10.1002/ejhf.876

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