Double-blind randomised placebo-controlled dose-efficacy study of sustained release verapamil in chronic stable...

The efficacy and tolerability of sustained release verapamil (Securon SR) was investigated in twenty-four patients with chronic stable angina. Patients entered four randomised, double-blind treatment periods, each lasting one week of verapamil-SR 240 mg once daily, 360 mg once daily, 240 mg twice daily, and matching placebo. Four patients were withdrawn, but in one instance this was attributable to side effects from verapamil. Among the remaining twenty patients, mean frequency of angina fell from 4.25 episodes during the last five days of placebo to 2.35, 2.6 and 1.3 episodes during respective active treatments (all P less than 0.001). Compared with placebo the median percentage increase in time to 1 mV ST depression during treadmill exercise (12 hours post dose) was significant only with the regimen of verapamil-SR 240 mg given twice daily at +11% (P = 0.04). Total duration of exercise was also significantly longer and maximum ST depression significantly less only with the twice daily treatment (704 + 186 sec vs 648 + 203 sec; P = 0.03, and 1.75 + 0.73 mm vs 2.15 +/- 0.62 mm; P = 0.02). Side effects, predominantly constipation, breathlessness, and swollen ankles, occurred most frequently with verapamil-SR 360 mg. Thus, sustained release verapamil is well tolerated and effective in the treatment of angina. A regimen of 240 mg given twice daily emerges as superior to once daily treatments for 24-hour prophylaxis of angina.