EDMONTON, Alberta -- October 30, 2009 -- A large post hoc subanalysis of a large international study has associated ivabradine with highly significant reductions in major cardiac events among patients with heart failure experiencing angina, according to data presented at the 2009 Canadian Cardiovascular Congress (CCC).
Analysis of ivabradine in this way was not specified in the original design of the Morbidity-Mortality Evaluation of the If Inhibitor Ivabradine in Patients With Coronary Disease and Left Ventricular Dysfunction (BEAUTIFUL) study, but the large and impressive risk reductions in a relatively large patient cohort suggest that ivabradine deserves a second look -- at least in some subgroups with coronary artery disease.
"BEAUTIFUL found no impact of ivabradine on the primary endpoint in the overall population, but our results indicate that this agent can prevent major cardiovascular events in patients with LV [left ventricular] systolic dysfunction who present with angina," reported Jean-Claude Tardif, MD, Montreal Heart Institute, Montreal, Quebec, on October 28.
In the BEAUTIFUL trial, ivabradine, an inhibitor of If channel, did not fulfil the hypothesis that lowering the heart rate could reduce events in the overall LV systolic dysfunction population with coronary artery disease, but there was a benefit observed in those patients who entered the study with a heart rate greater than 70 beats per minute (BPM).
This new subanalysis was limited to the 1,507 (13.8% of the original 10,917 patients) whose limiting symptom at baseline was angina. A further stratification in this new analysis was included for the 712 patients in the angina cohort that had a baseline heart rate of 70 BPM or greater.
Of the 1,507 patients with angina, 734 received ivabradine 5 mg twice-daily, which was uptitrated to a target dose of 7.5 mg twice daily, and 773 patients received placebo. Other than angina at baseline, the characteristics of this subgroup were very similar to those of the BEAUTIFUL trial overall.
At a mean of 18 months of follow-up, ivabradine was associated with a 24% reduction (hazard ratio [HR] 0.76; 95% confidence interval [CI], 0.58-1.0; P = .05) in reaching the primary composite endpoint of cardiovascular death, admission to hospital for acute myocardial infarction (MI), and admission to hospital for new onset or worsening heart failure relative to placebo. The relative reduction for hospitalisation for MI, however, was 42% (HR 0.58; 95% CI, 0.37-0.92; P = .021), and in the subgroup that also had an elevated heart rate, there was a relative 73% reduction (HR 0.27; 95% CI, 0.11-0.66; P = .002) in risk of MI. Patients with angina and an elevated heart rate also had a 59% reduction (HR 0.41; 95% CI, 0.17-0.99; P = .040) in revascularisation.
"The results suggest ivabradine may be helpful to reduce major cardiovascular events in patients with stable coronary artery disease and limiting angina, and this will be tested specifically in the SIGNIFY [Study Assessing the Morbidity-Mortality Benefits of the If Inhibitor Ivabradine in Patients With Coronary Artery Disease] trial," Dr. Tardif concluded.
The CCC is co-hosted by the Canadian Cardiovascular Society and the Heart and Stroke Foundation of Canada.
[Presentation title: Effect of Ivabradine on Cardiovascular Outcomes in Patients With Stable Coronary Artery Disease and Left Ventricular Dysfunction With Limiting Angina: A Subgroup Analysis of the BEAUTIFUL Trial. Abstract 925]
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