Sustained release verapamil, a once daily preparation: Objective evaluation using exercise testing, ambulatory monitoring and blood levels in patients with stable angina

The efficacy of a once daily, sustained release formulation of verapamil (Verapamil SR, 360 mg) was evaluated in 19 patients with chronic angina pectoris using a double-blind placebo-controlled crossover protocol. Evaluation by exercise testing, 24 hour electrocardiographic ambulatory monitoring and blood drug level assays was performed at the end of each 2 week phase, 21 to 23 hours after the last dose. After the crossover protocol, all patients were given sustained release verapamil for 4 weeks and the evaluation was repeated. Exercise time (mean ± SEM) increased from 7.4 ± 0.6 minutes with placebo to 9.6 ± 0.8 minutes with verapamil (p < 0.001) and to 9.5 ± 0.7 minutes (p < 0.001) after 4 weeks of therapy. The mean time to 1 mm ST depression also increased significantly, from 4.5 ± 0.4 and 4.8 ± 0.5 minutes in bipolar leads CM5and CC5, respectively, with placebo, to 5.5 ± 0.6 (p < 0.05) and 6.2 ± 0.5 minutes (p < 0.01) with verapamil. Maximal ST depression and rest and peak heart rates were not altered significantly. The mean rate-pressure product was 208 ± 9.9 with placebo and decreased to 189 ± 7.7 (p < 0.05) with verapamil but rose to 200.6 ± 10.4 (p = NS) after 4 weeks of therapy.The mean hourly heart rates were lower with the drug than with placebo throughout the 24 hour period but there was no significant bradycardia, arrhythmia or heart block. Episodes of ambulatory ST segment depression were also decreased by sustained release verapamil. Blood levels at 21 to 23 hours after the last dose were within the therapeutic range. The data indicate that this formulation of verapamil is effective when administered once daily