Efficacy of nifedipine therapy for refractory angina pectoris

Nifedipine is a calcium-channel blocking agent that has been effective for patients with angina pectoris when used as single-agent therapy and as part of a combination regimen with conventional antianginal therapy. However, the efficacy of nifedipine in patients with angina refractory to maximum tolerated conventional therapy has not been extensively studied. We present experience using nifedipine in the treatment of three distinct subsets of patients with refractory angina pectoris. One hundred twenty-seven patients with Prinzmetal's variant angina and documented coronary vasospasm were treated with nifedipine after experiencing an inadequate response to conventional therapy. Nifedipine, 40 to 160 mg daily, reduced the mean weekly rate of angina attacks from 16 to 2 (p < 0.001). In 63% of the patients complete control of angina attacks was achieved, and in 87% the frequency of angina was reduced by at least 50%. Nifedipine therapy was well tolerated, and the beneficial response persisted for the 9 months of follow-up. Nifedipine therapy was added to a second group of 11 consecutive patients with refractory episodes of recurrent rest ischemia following acute myocardial infarction. Prior to infarction all the patients had a history of exertional angina only; yet following the infarction, episodes of recurrent ischemia occurred at rest in spite of maximal medical management with beta blockers and/or nitrate preparations. With maximum tolerated conventional therapy the heart rate was lowered to a mean of 65 beats/min and the blood pressure to a mean of $\text{109}\text{70}\text{mm Hg}$. The episodes of rest ischemia were prevented in all but one patient by the addition of nifedipine (mean daily dose 60 mg, range 40 to 120 mg) without causing a change in heart rate or blood pressure. Two patients continued to have myocardial ischemia with minimal exertion, although resting pains were abolished, and they underwent coronary bypass surgery for rellef of exertional pain. Only one patient continued to have episodes of ischemia at rest, and bypass surgery was necessary for pain relief. The other eight patients have been managed medically for a mean of 5.4 months and have remained pain free on combined regimens of nifedipine, beta blockers, and/or nitrate preparations. The third group of patients treated with nifedipine is composed of 239 patients with severe classic exertional angina pectoris without a suspicion of superimposed coronary vasospasm. The anginal episodes in these patients were refractory to maximum tolerated conventional therapy; however, the addition of nifedipine (mean daily dose 60 mg, range 40 to 120 mg) reduced the mean weekly angina attack rate from 20.8 to 6.4 (p < 0.00001). Although only 11% of patients had complete prevention of angina during nifedipine therapy, a total of 70% experienced a reduction in angina frequency of at least 50%. We conclude that the addition of nifedipine therapy may provide further benefit for patients with angina pectoris refractory to maximum tolerated conventional therapy. Randomized, placebo-controlled studies are necessary to confirm the efficacy of nifedipine therapy in patients with refractory angina and to clarify the mechanism of the beneficial response.