Comparison of nicorandil and atenolol in stable angina pectoris

Abstract

The efficacy of nicorandil was compared with atenolol in 37 patients with chronic stable angina using a randomized, placebo-controlled, parallel study design. After a single-blind placebo phase, patients were randomized to receive nicorandil or atenolol using a double-dummy technique. Patients took nicorandil 10 mg twice daily or atenolol 50 mg once daily for the first 3 weeks, and if no adverse effects were encountered they took nicorandil 20 mg twice daily or atenolol 100 mg once daily, for the final 3-week phase. Treadmill exercise tests were performed at the end of each treatment phase immediately before and 2 hours after the morning dose of medication. Groups were demographically similar. Placebo exercise times were 7.06 (0.60) minutes (mean ± standard error of the mean) in the nicorandil group and 6.81 (0.47) minutes in the atenolol group. After 6 weeks, improvements in exercise time were before dosing: +1.47 (0.40) minutes with nicorandil (p < 0.005) and +1.33 (0.29) minutes with atenolol (p < 0.001). Improvements after therapy was administered were +2.45 (0.41) minutes with nicorandil (p < 0.001) and +2.37 (0.43) minutes with atenolol (p < 0.0001). Whereas, the predose peak exercise double product (heart rate X systolic blood pressure mm Hg/100) was reduced with atenolol (−43.6 units; p < 0.001), an increase (+7.56 units; difference not significant) was noted with nicorandil. One patient taking atenolol and 5 taking nicorandil developed persistent headaches. One subject with severe 3-vessel coronary artery disease had fatal myocardial infarction within 3 days of starting nicorandil, 10 mg twice daily. Nicorandil and atenolol produce comparable improvement in exercise time in patients with stable angina but the former does not reduce myocardial oxygen demand. This new agent may be beneficial in patients with angina in whom β blockers are contraindicated, although headache may be a problem in a significant minority of patients.