Long-term therapy with ivabradine in combination with beta-blockers in patients with stable angina pectoris and effect of beta-blocker background dose: results from the ADDITIONS 1-year follow-up

Abstract

Objectives: The non-interventional multicenter ADDITIONS study follow-up evaluated the effectiveness, safety, and effect on quality of life (QoL) of ivabradine (iva) in combination with betablockers over one year. Methods: Resting heart rate (HR), the number of angina attacks, nitrate consumption, and concomitant medications were documented in 901 patients with chronic stable angina treated with iva twice daily in flexible doses in combination with betablockers for one year. QoL was evaluated by the EQ-5D patient questionnaire at each visit. A descriptive statistical analysis was performed. Results: 901 patients (intention to treat, mean age 65.4±10.6 years, 58% male) with chronic stable angina were analyzed. 53% of the patients had undergone a PCI or CABG before and 35% had a history of myocardial infarction. All patients received betablockers (e.g. Metoprolol 41%, mean daily dose (mdd) 109.6 mg; Bisoprolol 39%, mdd 6.9 mg; Nebivolol 13%, mdd 4.9 mg; Carvedilol 7%, mdd 28.9 mg) and concomitant standard medication. At baseline, most patients (49%) were classified CCS grade II, mean HR was 86.1±12.6 bpm, a mean of 1.7±2.2 angina attacks per week were reported, consumption of short-acting nitrates was 2.3±3.2 units per week, and the EQ-5D index was 0.66±0.28. After one year, iva (mean dose 12.53±2.84 mg per day) had reduced HR by 20.7±14.0 bpm to 65.4±8.8 bpm, the number of angina attacks by 1.4±2.5 per week (p<0.0001, Wilcoxon signed rank test), and nitrate consumption by 1.9±3.1 units per week (p<0.0001), had improved EQ-5D index by 0.18±0.27 (p<0.0001), and most patients (63%) were classified CCS grade I. HR reduction and improvement of angina symptoms by iva was similar in three subgroups defined by betablocker background dose (<50%, 50% to 99%, and ≥100% of recommended target dose): see table. View this table: Table 1 Conclusion: Over one year the combination of iva with betablockers in clinical practice not only effectively reduced HR, number of angina attacks, and nitrate consumption, but also improved QoL and CCS class in patients with stable angina. Moreover, the treatment effect of iva on HR and angina symptoms was independent of background betablocker dose.