Treatment of Stable Angina with a New Fixed-Dose Combination of Ivabradine and Metoprolol: Effectiveness and Tolerability in Routine Clinical Practice

INTRODUCTION: In this prospective, multicenter, observational cohort study, the effectiveness and tolerability of the first fixed-dose combination (FDC) formulation of the selective heart rate reducing agent ivabradine and the beta-blocker metoprolol was evaluated in stable angina pectoris (AP) patients in a clinical practice setting. METHODS: Stable AP outpatients received a FDC of ivabradine and metoprolol (b.i.d.) for 4 months, in addition to cardiovascular standard therapy. Resting heart rate (HR), number of angina attacks, short-acting nitrate consumption, severity of symptoms (assessed by patient judgment and documented by CCS score) and tolerability were documented. Medication adherence was assessed by a modified four-item Morisky questionnaire. Descriptive statistics were performed on all data. RESULTS: A total of 747 stable AP patients (mean age, 66.4 years, 62% male, 50% and 31% with previous PCI and myocardial infarction, respectively) were included. Apart from ivabradine and beta-blockers as free combination, most frequently used concomitant standard medications at baseline were aspirin (68%), statins (71%), ACEI/AT1-blockers (76%), diuretics (35%), and calcium antagonists (15%). Highly prevalent comorbidities were hypertension (86%), hyperlipidemia (65%), and diabetes (35%). After 4 months, switch to treatment with the FDC was associated with a significant reduction in mean HR by 10 bpm. Proportion of patients with ≥ 1 angina attacks/week decreased from 38 to 7%. Patients in CCS class 1 increased (25 to 63%), while they decreased in CCS class 3 (19 to 5%). Medication adherence was also significantly improved (p < 0.001 for all changes from baseline). Mostly mild adverse events were documented in 5.4% of patients. CONCLUSIONS: In these stable AP patients in a real-life setting, treatment with a FDC of ivabradine and metoprolol was associated with reduced HR and angina symptoms, while exercise capacity (CCS score) was improved. These effects may be mainly mediated by the increased medication adherence of patients observed with use of the FDC formulation. FUNDING: Servier TRIAL REGISTRATION NUMBER: ISRCTN51906157.