COMPARATIVE EVALUATION OF THE EFFECT OF COMBINATION THERAPY WITH BISOPROLOL BISOPROLOL MONOTHERAPY AND IVABRADINE ON LEFT VENTRICULAR SYSTOLIC FUNCTION, CENTRAL HEMODYNAMICS IN PATIENTS WITH CHRONIC ISCHEMIC HEART DISEASE

Purpose. To assess the impact of monitoring heart rate using a combination of bisoprolol and ivabradine compared with monotherapy with higher doses of bisoprolol on left ventricular systolic function, central hemodynamics in patients with CCHD moderately reduced ejection fraction. Methods: In single-blind, parallel-group study 78 pts aged < 60 years (54±2,3) in sinus rhythm >70 bpm with CAD (stable angina CCS class I-II), documented MI>3 months, mild hypertension and mean EF of 38-45%, treated with ACE inhibitors and Bs 2,5 mg od or BB naive, were randomized into 2 groups. In Group 1 (n=40) Bs was uptitrated to 5mg pd and Iv was added (5mg bid uptitrated to 7,5 mg bid, 12,4±0,49mg pd), in Group 2 (n=38) Bs was uptitrated to 10 mg od (9,1 ±0,35 mg pd). At baseline (M0) and 2 months (M2), symptom-limited treadmill test ? TT (Bruce protocol) was performed and EF, peak systolic velocity, septal mitral annulus site (Slat) and ratio of early mitral flow velocity to annulus velocity (E/E’) by TDI and plasma NT proBNP by ELISA were assessed. Results: Resting HR and systolic BP were similar in both groups at M0 (78,6±3,59 vs 81,4±3,7 bpm and 135,4±5,8 vs 132,4±5,8 mmHg), and at M2 (66,4±2,93 vs 64,9±2,91 bpm and 124,2±5,4 vs 125,2±5,7 mmHg, p>0,05). TT, EF, Slat, E/E’ and NTproBNP results (M±m) see in table. Fatigue and/or dyspnea were predominant reason for TT termination in both groups at M0 (55% vs 47,5%) and at M2 (68,6% vs 60%). Conclusions: 1. Patients <60 years with CCHD and moderately reduced vWF equivalent control heart rate at rest after 2 months, treatment with the combination of ivabradine and bisoprolol, compared with monotherapy with bisoprolol was associated with improved segmental systolic function by tissue Doppler indices in the absence of significant changes in ejection fraction. The use of the combination of ivabradine and bisoprolol has less pronounced vasoconstrictor effects than monotherapy with bisoprolol, which is manifested in the improvement of central hemodynamics, in particular, augmentation pressure, aortic systolic blood pressure, augmentation index, as well as indicators of vascular stiffness. Monotherapy with bisoprolol has a pronounced antiarrhythmic effects in alignment with the combination of ivabradine and bisoprolol, at the same time, leads to a more stringent reduction in heart rate, which can potentially contribute to the development of Brady arrhythmias and requires more in-depth study, while, heart rate dependent effect of ivabradine It makes it softer impact, and reducing the minimum heart rate less pronounced.