NEW YORK (Reuters Health) – By lowering heart rate, the selective sinoatrial current inhibitor ivabradine improves outcomes in patients with chronic heart failure and an elevated heart rate, according to findings reported August 29 at the European Society of Cardiology Annual Congress in Stockholm and online in The Lancet.

“As patients with chronic heart failure (CHF) remain at high risk, new therapies are important,” Dr. Karl Swedberg commented via email. “In patients already on an ACE-inhibitor and a beta-blocker (or if not tolerated) and with elevated heart rate, ivabradine provides added benefits above and beyond a beta-blocker.”

Dr. Swedberg, with the Sahlgrenska Academy, University of Gothenburg, in Sweden and colleagues note in their paper that ivabradine does not affect myocardial contractility, even in patients with impaired systolic function. “We designed the Systolic Heart failure treatment with the I-f inhibitor ivabradine Trial (SHIFT),” they write, “with the aim of evaluating the effect of ivabradine in addition to guidelines-based treatment on cardiovascular outcomes, symptoms, and quality of life in patients with chronic heart failure and systolic dysfunction.”

The results are based on 6505 CHF patients with resting heart rates over 70 bpm (mean 79.9 bpm). Most (approximately 90%) of them were on a beta-blocker, but only about a quarter could tolerate the full target dose.

Participants were randomly assigned to ivabradine or placebo. At 1 month, at the end of titration, the mean heart rates in the two groups had fallen to 64.5 and 75.4 bpm, respectively. This 10.9-bpm difference narrowed somewhat to 9.1 bpm at 1 year, and to 8.1 bpm at 32 months.

After a mean follow-up of 22.9 months, the primary endpoint of cardiovascular death of hospitalization for worsening heart failure was reached by 24% of the ivabradine group and 29% of the placebo group (hazard ratio 0.82, p<0.001). “On the basis of this absolute risk reduction, 26 patients would need treatment for 1 year to prevent one cardiovascular death or one hospital admission for heart failure,” Dr. Swedberg and colleagues calculate. Asked if ivabradine should become the standard of care in this setting, Dr. Swedberg responded: “It is safe and simple to titrate. It should be considered in all patients with CHF remaining with high heart rate. Thus, SHIFT has helped to advance clinical medicine further.” “However,” writes Dr. John Teerlink from the University of California, San Francisco, in a commentary, “whether ivabradine can improve outcomes in addition to optimally managed heart failure therapies or its benefits relative to other therapies, especially beta blockers, remains unknown. The results from SHIFT provide the basis for additional trials to test these important and clinically relevant question.” He concludes, “Until these questions are answered, the place of ivabradine in heart failure therapies remains unclear.” Reference:
Ivabradine and outcomes in chronic heart failure (SHIFT): a randomised placebo-controlled study


Lancet 2010;