Abstract

Mildronate (M; 3-(2,2,2-trimethylhydrazinium) propionate), a competitive inhibitor of carnitine biosynthesis, promotes cellular protection and energy supply during ischemia, including improve­ment of myocardial contractility. The purpose of this double-blind, randomised, placebo- and digoxin-controlled clinical trial was to compare the results of a six-week treatment of 120 patients with chronic heart failure (CHF), functional class II consistent with the classification of New York Heart Association (NYHA), due to coronary heart disease, using three doses of M: 0.5 g daily (M 0.5 group), 1.0 g daily (M 1.0 group), and 1.5 g daily (M 1.5 group), as well as digoxin, 0.5 mg daily (D group) and placebo (P group), by assessing symptoms, exercise tolerance (using bicycle ergometry), myocardial contractility (using EchoCG), and peripheral circulation (using venous oc­clusion pletismography). In all Mildronate-patient groups and in the D group, 59-78 % of patients showed a transition from NYHA II to NYHA I, compared to 27 % in the P group. Maximal workload (ML) in the M 1.0 and M 1.5 groups increased by 15.5±4.4 and 13.3±5.4 W, exercise time (ET) in the M 1.0 group by 1.9±0.4 min, and performed work (PW) in M 1.0 by 11.7±3 kJ, in comparison with the respective baseline (initial value before treatment). In contrast to the D group, mean ST segment deviation (in electrocardiogram) (STdev) at exercise maximum in all M groups did not in­crease. The ejection fraction (EF) in the M 1.0 group increased by 7.3±2 %, in the M 1.5 group by 6.1+1.5 %, in the D group by 6.1±2.1 %, in comparison with the baseline values. Minimal arterial resistance (Rmin) during reactive hyperemia in the M 0.5, M 1.0, and M 1.5 groups was dimin­ished by 1.0±0.3. 0.6±0.26, and 0.7+0.25 peripheral resistance units (PRU), respectively (P<0.05 vs P). No significant differences from the P group in changes of parameters of myocardial contractility and exercise tolerance in M 0.5 group were observed. Mildronate, in doses of 1.0 and 1.5 g per day, improved symptoms, exercise tolerance, and myocardial contractility, diminished the contractile activity of vascular smooth muscles, and it protected myocardium from ischemisation. Therefore, Mildronate could be a useful drug for the treatment of CHF.