“Maximal” drug therapy is not necessarily optimal in chronic angina pectoris

Beta-adrenergic blocking agents, nitrates and calcium channel antagonists are effective in treating angina pectoris, but much remains unknown about how they act in combination. Consequently, treadmill exercise was used to assess the relative efficacy of nifedipine or isosorbide dinitrate, or both, in 19 patients with stable angina receiving propranolol. Propranolol therapy was continued and either placebo, nifedipine (20 mg), isosorbide dinitrate (20 mg) or both drugs were given randomly 1'/z hours before exercise in a double-blind trial. In 16 patients who completed the protocol, heart rate at rest during propranolol therapy was 53.7 ± 1.9 beats/min (mean ± standard error of the mean); it increased 4.6 ± 1.2 beats/min with the addition of nifedipine (p < 0.01), but was unchanged with isosorbide dinitrate or both combined. Compared with values during treatment with propranolol alone, systolic blood pressure at rest decreased with each vasodilator individually and when combined. Rate-pressure product at maximal exercise was the same with all combinations. Exercise duration was 467 ± 50 seconds with propranolol, increased to 556 ± 47 seconds with isosorbide dinitrate (p < 0.05) and to 636 ± 50 seconds with nifedipine (p < 0.001). Exercise duration with all three drugs was 597 ± 47 seconds (p < 0.01 compared with propranolol alone). The improvement with nifedipine was greater than with isosorbide dinitrate (p < 0.05) but exercise duration was not significantly different with the combination of these drugs than when either drug was used alone. Exercise duration was actually worse in 9 of 16 patients when all three drugs were given than with the two drug combination of propranolol and nifedipine. Thus, in an individual patient, combining all three agents does not necessarily optimize therapy.