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GW24-e2957 Efficacy of ivabradine in combination with metoprolol versus uptitration of metoprolol in patients after Q-wave myocardial infarction with early left ventricular systolic dysfunction
  1. Yao Xu,
  2. Andrii Bezrodnyi
  1. The Bogomolets National Medical University

Abstract

Objectives The purpose of the study was to evaluate the effect of combination of ivabradine with metoprolol tartrate versus uptitration of metoprolol tartrate on left ventricular (LV) systolic function and plasma levels of N-terminal pro atrial natriuretic peptide (NT-proANP) in patients after first Q-wave myocardial infarction (MI) with early LV ejection fraction (LVEF) < 45%.

Methods This randomized single-blind, parallel-group study included 106 patients with a first Q-wave MI and LVEF < 45%, sinus rhythm > 80 bpm, Killip class I-II, hospitalized within 24 hours of the onset of symptoms. Patients in group 1 (n = 60) from day 1 received metoprolol tartrate, after 5 days the dose of which increased to 25 mg bid (average daily dose 58.8 ± 1.6 mg), and from day 5 received 2.5 mg of ivabradine bid, the dose of which increased to 7.5 mg bid (average daily dose 12.7 ± 0.4 mg). Patients in group 2 (n = 46) received metoprolol tartrate, the dose of which titrated to 75 mg bid (average daily dose 115.4 ± 6.4 mg). The patients of both groups did not differ by age, sex, incidence of such diseases in anamnesis as hypertension, diabetes and the frequency of the localization of MI and Killip class II at admission, as well as in regards of clinical characteristics, reperfusion and initial treatment (all p>0.05). Besides LV end-diastolic index (LVEDI) and LVEF at day 1, day 25 and month 6, and plasma levels of NT-proANP (ELISA) at day 2, day 25 were estimated.

Results Resting heart rate was reduced in both groups (at day 1 – 87.9 ± 1.7 vs. 87.3 ± 1.6 bpm, at day 25 – 61.8 ± 1.5 vs. 63.4 ± 1.6 bpm, after 6 months – 61.5 ± 1.5 vs. 62.7 ± 1.5 bpm, all p>0.05). In group 1, LVEDI at day 25 was improved from 72.5 ± 1.5 to 76.6 ± 1.4 ml/m2 (p<0.05), and after 6 months was 75.8 ± 1.5 ml/m2 (p>0.05 compared with the baseline). In group 2, LVEDI initially was 72.8 ± 1.4 ml/m2, at day 25 increased to 81.4 ± 1.5 ml/m2 (p<0.01) and after 6 months – to 82.4 ± 1.5 ml/m2 (p<0.01). In group 1 at day 25, LVEF increased from 38.9 ± 1.5 to 46.7 ± 1.5%, after 6 months – up to 48.5 ± 1.4% (all p<0.01). Throughout the study period in group 2 LVEF did not change significantly (at day 1 – 38.8 ± 1.4%, day 25 – 39.7 ± 1.4% and after 6 months – 40.9 ± 1.5%, all p>0.05). But the difference in LVEDI and LVEF from 25 day of treatment between the 2 groups was show significantly (p<0.01). Plasma levels of NT-proANP in group 2 did not change significantly up to day 25 (3492.8 ± 278.5 vs. 3546.5 ± 212.7 pmol/l, p>0.05). However in group 1, it was decreased from 3504.2 ± 295.2 to 2315.7 ± 201.5 pmol/l (p<0.01) and significantly lower than in group 2 at day 25 (p<0.01).

Conclusions With the same negative chronotropic effects, the addition of ivabradine to metoprolol tartrate in patients after Q-wave MI with early moderate LV systolic dysfunction, Killip class ≤ II and sinus rhythm > 80 bpm at admission, in comparison with uptitration of metoprolol tartrate, was associated with improvement of LV systolic function, prevention of early (< 1 month) and late (6 months) LV dilatation and decrease of plasma NT-proANP by day 25.

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