AGE-RESPONSE EFFECTIVENESS OF GALLOPAMIL FOR THE TREATMENT OF MYOCARDIAL EXERTIONAL ISCHEMIA - MEDIUM-TERM RANDOMIZED CROSS-OVER DOUBLE-BLIND PLACEBO-CONTROLLED TRIAL

We evaluated the efficacy and safety of gallopamil 150 mg daily in mid dle-aged and elderly patients with stable exertional ischemia, using a medium-term randomized double-blind cross-over placebo-controlled tri al. Twenty middle-aged patients (52.8+/-6 years; range 38-61 years) an d 14 elderly patients (67.4+/-2.8 years; range 65-73 years) with stabl e exertional ischemia underwent a bicycle exercise test. After a run-i n period, both groups received treatment with either placebo or gallop amil 50 mg tid for 28 days. At the end of this time, each patient cros sed over to the alternate regimen. Gallopamil significantly reduced he art rate, blood pressure and rate pressure product (from 15.37+/-2.7 t o 13.65+/-4.16 Ux10(-3), p<0.01) in elderly patients at submaximal exe rcise, but had no effect in middle-aged patients (from 14.52+/-4.45 to 13.49+/-3.77 Ux10(-3); p=NS). At peak exercise, none of the hemodynam ic parameters was modified with gallopamil in either group. At peak ex ercise, both middle-aged and elderly patients achieved rate-pressure p roducts similar to those reached during placebo at higher work loads. Exercise duration and maximal work load significantly increased in bot h groups. Electrocardiographic signs of ischemia were favorably influe nced by gallopamil in both groups (from 1.39+/-0.5 mm to 0.76+/-0.73 m m; p<0.001 in the middle-aged patients and from 1.5+/-0.34 mm to 1+/-0 .76 mm; p<0.01 in the elderly patients). Time of onset of ST segment d epression greater than or equal to 1 mm was prolonged (from 363+/-143 sec to 530+/-138 sec; p<0.001 in the middle-aged patients and from 306 +/-131 sec to 415+/-152 sec; p<0.001 in the elderly patients), while S T segment depression at submaximal and peak exercise was reduced. Only 2 patients in each group reported side effects, one had palpitations, and one headache. One patient in the elderly group showed a Ist degre e atrio-ventricular block after gallopamil. No dropout runs recorded, Our data suggest a relationship between age and mechanism of action of gallopamil in patients with exertional ischemia. Gallopamil exerted i ts anti-ischemic action in elderly patients through a prevalent reduct ion in rate pressure product (an indirect measure of myocardial oxygen consumption), while in the middle-aged patients through an improvemen t in myocardial oxygen supply (no change in rate pressure product).