Ivabradine (Procorala), a heart-rate-lowering medication, considerably lowers cardiovascular death and hospitalization risk when added to standard treatment in patients suffering from heart failure and a high heart rate (pulse rate), an Article reveals in the medical journal The Lancet. Details of a clinical trial were presented at the European Society of Cardiology Annual Congress 2010, Stockholm, Sweden.
The researchers reported that for patients with systolic heart failure and reduced left ventricular function who were stable on beta blocker medication, the heart-rate-reducing effects of ivabradine lowered death and heart failure hospitalization risk considerably, when compared to a placebo.
The Systolic Heart Failure treatment with the If ivabridine Trial (SHIFT) involved 6,505 patients from 27 countries. They were randomly selected to receive:
- Ivabradine – initial 5 mg dose, up to a maximum of 7.5 mg twice daily (3,241 patients)
- A placebo (3,264 patients)
In both cases they also received standard heart failure treatments.
The researchers report that major heart failure outcomes were 18% lower for those on ivabradine compared to participants on the placebo.
21% of the placebo patients were hospitalized with worsening heart failure, versus 16% in the ivabradine group.
5% of patients in the placebo group died of heart failure, compared to 3% in the eivabradine group.
The researchers add that ivabradine was found to be safe and generally well tolerated. In fact, 3,847adverse events reported in the placebo group compared to 3,388 in the ivabradine group.
The authors concluded:
Our results support the importance of heart-rate reduction with ivabradine for improvement of clinical outcomes in heart failure and confirm that heart-rate modulation can interfere with progression of disease.
Michael Böhm, Universitätsklinikum des Saarlandes, Germany, along with the SHIFT authors, examined whether raised resting heart rate at the beginning of the study was a risk factor for subsequent cardiovascular events. Analysing data from the SHIFT study, they worked out the probability of cardiovascular death and hospitalization for worsening heart failure in patients with highest (≥87 bpm) and the lowest (70-72 bpm) pretreatment heart rates, and after one month of treatment with ivabradine.
Patients on the placebo with the most elevated heart rates had more than double the risk of dying or experiencing a cardiovascular event. Each 5 pmn increase from the start of the study correlated with a 16% increased risk of cardiovascular death or hospitalization.
The researchers also found a direct link between heart rate at 28 days after treatment with ivabradine and cardiac outcomes. 17.4% of the participants with heart rates below 60 bpm at 28 days had fewer events during the study, compared to 32.4% ofpatients with heart rates.
The authors said:
There is a continuous direct association between baseline heart rate and outcomes. The risk is modified and significantly decreased by ivabradine. The effect of ivabradine on heart rate is most pronounced in patients with high baseline values and correspondingly high reductions in heart rate due to ivabradine treatment.
(conclusion) The lowest heart rates achieved on treatment are associated with the best outcomes, and because the incremental benefit of ivabradine was obtained by titration of the drug to heart rates lower than 60 bpm, we estimate that this target, when tolerated, should be pursued by patients with chronic heart failure.
John Teerlink from the University of California, San Francisco, USA, in a Comment in The Lancet, said:
Ivabradine therapy might reduce heart-failure hospitalisations when added to contemporary heart-failure therapies. However, 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 questions.. Until these questions are answered, the place of ivabradine in heart failure therapies remains unclear.
Prof Karl Swedberg MD, Prof Michel Komajda MD, Prof Michael Böhm MD, Prof Jeffrey S Borer MD, Prof Ian Ford PhD, Ariane Dubost-Brama MD, Guy Lerebours MD, Prof Luigi Tavazzi MD.
The Lancet, Early Online Publication, 29 August 2010
doi:10.1016/S0140-6736(10)61198-1
Comment:
John R Teerlink
The Lancet, Early Online Publication, 29 August 2010
doi:10.1016/S0140-6736(10)61314-1
Written by Christian Nordqvist