Silent ischemic interval on exercise test is a predictor of response to drug therapy: A randomized crossover trial of metoprolol versus diltiazem in stable angina

Abstract

Background and hypothesis: There is no method available to predict the relative antianginal efficacy of beta blockers and calcium-channel antagonists. The present study was undertaken to assess the role of silent ischemic interval (SII) on exercise treadmill test (ETT) as a predictor of response to therapy with metoprolol and diltiazem in patients with stable angina. Methods: Thirty-four patients with stable angina were divided into two groups depending upon the presence or absence of an SII gap of at least 1 min between onset of ST depression and appearance of angina on ETT. Metoprolol (50-100 mg twice daily) and diltiazem (60-120 mg three times daily) were randomly assigned for 6 weeks to patients in each group, and then patients were crossed over for further 6 weeks after a washout period of 2 weeks. Antianginal efficacy was assessed by clinical and exercise parameters. Results: In patients with SII, the clinical responder rate was better with metoprolol than with diltiazem (90 vs. 60%, respectively), and on ETT, metoprolol produced significant improvement in the total exercise time (p < 0.01), time to 1 mm ST depression (p < 0.01), time to angina (p < 0.01), and a significant decrease in peak rate-pressure product (p < 0.001), whereas diltiazem had no significant effect on exercise parameters. However, in patients without SII, metoprolol and diltiazem had a similar clinical responder rate (57%), and both produced a significant increase in total exercise time (p < 0.01), time to 1 mm ST depression (p < 0.01), and time to angina (p < 0.01). In addition, metoprolol had a significant effect on peak rate-pressure product (p < 0.001). Conclusion: Silent ischemic interval on ETT can be a predictor of response to antianginal therapy in stable angina, as patients with SII respond better to metoprolol and those without SII respond equally to both metoprolol and diltiazem.