[New opportunities to improve the treatment effectiveness of patients with stable angina]

Aim To study the antianginal and heart rate slowing effects in patients with stable angina (SA) who failed to achieve the heart rate (HR) goal and were switched from the beta-blocker (BB) metoprolol tartrate to a combination of metoprolol tartrate and ivabradine.Materials and methods The study included 54 patients with SA not higher than functional class (FC) III (35 (64.8 %) men and 19 (35.2 %) women) aged 59 [48; 77] years. Prior to the study start and at 4 and 8 weeks of follow-up, electrocardiography (ECG) and 24-h ECG monitoring (24h-ECGM) were performed for all patients. The follow-up period duration was 8 weeks. The antianginal and heart rate slowing effects of therapy were clinically evaluated by a decrease in frequency of anginal attacks and patients' requirement for nitrates, a decrease in HR, and the effect on 24h-ECGM indexes characterizing myocardial ischemia. At the first stage, all patients were prescribed metoprolol tartrate (Egilok®, Egis, Hungary) 25 mg twice a day. Patients with resting HR still higher than 70 bpm after 4 weeks of treatment were switched from metoprolol tartrate to a fixed ivabradine/metoprolol combination (Implicor®, Servier, France) 5 / 25 mg twice a day. Thus, based on achieving/ non-achieving the HR goal, two groups of patients were formed. Statistical analysis was performed with a STATISTICA 10,0 software package.Results After 4 weeks of therapy with metoprolol tartrate 25 mg twice a day, 18 (33.3%) patients of group 1 achieved the HR goal of 70 bpm, while  36 (66.7%) patients of group 2 did not achieve the goal. For further correction of HR, patients of group 2 were switched from metoprolol tartrate to ivabradine/metoprolol 5 / 25 mg twice a day. After 4 weeks of the ivabradine/metoprolol treatment, 31 (86.1 %) patients achieved the HR goal with median resting HR of 62 [56; 70] bpm. The number of angina attacks decreased from 6 [3; 8] to 2 [1; 3] per week (р<0.001). 24hECGM showed that the mean diurnal HR decreased from 81 [76; 96] to 66 [56; 76] bpm (р<0.001); mean night HR decreased from 69 [73; 80] to 52 [43; 60] bpm (р=0.012); and the ischemic ST segment depression was absent.Conclusion Only 33.3% of patients with stable angina achieved the HR goal on metoprolol tartrate 25 mg twice a day. Supplementing the beta-blocker metoprolol tartrate at the same dose with ivabradine allowed 86.1% of patients to achieve the HR goal and exerted a pronounced anti-anginal effect.