[Decrease in the sensitivity to the anti-ischemic effect of propranolol and prospects for correcting it in patients...

To study incidence of low sensitivity to an antiischemic effect of propranolol and feasibility of its correction with a metabolic drug--trimetazidine.

Paired treadmill and bicycle exercise tests were made until depression of segment ST > 1 mm and a typical angina episode. The trial included 147 men with ischemic heart disease, stable angina pectoris (functional class II-III). The antiischemic effect of propranolol single doses 40 or 80 mg were assessed in 117 patients. Single doses of propranolol 40 mg, trimetazidine 20 mg and their combination were examined for an antiischemic effect in 30 patients. The absence of the above effect of propranolol was stated in 20 patients who participated in a double blind, randomised, placebo-controlled study with conduction of 2-week courses of regular administration of propranolol in a dose 120 mg/day, trimetazidine 60 mg/day and their combination. Echo-CG was made initially and in the end of each course.

Propranolol's antiischemic effect of a single dose 40 mg was not found in 45.3% patients, 40-80 mg--in 21%. Among 20 patients without effect of the single propranolol dose, an increment of the threshold load made up 20.7 +/- 15.7 s, after intake of trimetazidine 16.3 +/- 18.6 s. The combination of these drugs significantly increases the increment of the threshold load duration to 90.8 +/- 80.4 s. The same picture was observed in the course treatment. The above increment in the course administration of propranolol was 46.3 +/- 15.3 s, of trimetazidine 22.8 +/- 20.2 s, of their combination 122.7 +/- 21.8 s (p = 0.02). In the absence of propranolol effect, echo-CG registered deterioration of disorder of left ventricular diastolic function. 10 patients with effect of the single propranolol dose this deterioration was not observed in combined use of propranolol and trimetazidine.

The antiischemic effect of propranolol in a single dose 40 mg was not recorded in about half of the examined anginal patients. Combined use of propranolol and trimetazidine in cases with no propranolol effect provides a synergetic effect both in single and course administration.