Nifedipine in the treatment of Prinzmetal's (variant) angina.

The clinical response to therapy with the calcium-blocking agent nifedipine was assessed in 12 patients with variant angina pectoris who were 44 to 67 years old. Five patients had vasospasm of the left anterior descending coronary artery, and seven had spasm of a dominant right coronary artery. Before nifedipine therapy, the frequency of anginal attacks per 24 hour period ranged from 1 to 12, with ventricular tachycardia accompanying ischemic episodes in 7 of 12 patients and high grade atrioventricular block occurring in 2 patients. After therapy with nifedipine, 11 of 12 patients had initial relief of symptoms, and 7 of the 11 had long-term relief. Withdrawal of nifedipine led to recurrence of angina on six occasions in four patients. Provocative testing in the cardiac catheterization laboratory by means of the cold pressor test in one patient and ergonovine maleate in another before and after nifedipine administration showed that this agent can block both alpha adrenergic- and regonovine-induced vasospasm. Nifedipine may have a significant role in the therapy of angina caused by coronary spasm.     

Prinzmetal's angina during cyclophosphamide therapy

The first case of cyclophosphamide-induced myocardial ischaemiawith electrocardiographically documented ST-segment elevation,T-wave inversion, arrhythmias, angina pectoris and cardiac decompensationis reported. The data suggest that cyclophosphamides inducesmyocardial ischaemia by eliciting coronary artery spasm.     

Prinzmetal's angina.

A 23-year-old man had Prinzmetal's variant angina. After strenuous exercise and isoprenaline infusion the electrocardiogram remained normal and the patient asymptomatic. Coronary angiography gave normal results which remained normal after administration of ergometrine. An injection of methacholine induced an attack.     

Prinzmetal's variant angina.

Two patients are described with a typical Prinzmetal's variant angina. Both patients were young, active males with angina of recent onset. They experienced angina only at rest and in one patient the angina had a cyclic character appearing only between 4 and 10 a.m. In both patients there was no correlation whatsoever between the angina pectoris and effort, emotion or change in temperature and the angina reacted promptly to nitroglycerine sublingually. The number of attacks and the intensity of the pain were increasing rapidly over a short period of time in both cases. The stenoses in both patients did not exceed 50% of the lumen of the coronary arteries, but coronary surgery has been performed on clinical grounds because both patients were completely disabled and one of them suffered from life-threatening dysrhythmias. For respectively 18 and 6 months after saphenous vein bypass surgery both patients have been symptom-free and able to resume their work. The problems concerning the diagnosis Prinzmetal's variant of angina pectoris are discussed.     

Prinzmetal's variant angina

Although the prevalence of variant angina pectoris is unknown, it appears to be substantially less common than typical, exertional angina and unstable angina at rest. The patient with variant angina typically complains of a pressure-like, squeezing retrosternal chest discomfort of several minutes duration. The diagnosis is secured by the occurrence of transient ST-segment elevation in association with chest pain, both of which resolve spontaneously or with nitroglycerin. After the diagnosis is made, the patient usually becomes symptom-free on calcium-channel blockers with or without long-acting nitrates. Although the long-term survival of these patients is excellent, an occasional individual with variant angina sustains a complication, most often myocardial infarction, a life-threatening arrhythmia, or sudden cardiac death.     

Absence of rebound from diltiazem therapy in Prinzmetal's variant angina

To determine the frequency of rebound anginal symptoms on abrupt withdrawal of calcium channel blocking agents, anginal symptoms were retrospectively examined in patients with Prinzmetal's variant angina abruptly withdrawn from diltiazem therapy as part of the design of a placebo-controlled multiple crossover trial. Rebound was defined as a return of anginal symptoms to levels exceeding those of the pretreatment baseline state. Values for daily frequency of angina were compared (after subtracting corresponding baseline values) between placebo periods following diltiazem periods and placebo periods following placebo periods. No intergroup differences existed between mean changes in daily frequency of angina from baseline value (-0.61 for placebo following diltiazem versus -1.10 for placebo following placebo) (p greater than 0.4). Furthermore, in 13 (28%) of 46 occurrences when placebo followed placebo, daily frequency of angina exceeded baseline value in the immediate 3 day period following placebo compared with 17 (21%) of 80 occurrences when placebo followed diltiazem. There was no increased rebound occurrence comparing high dose (240 mg/day) with low dose (120 mg/day) diltiazem therapy. No significant symptoms such as myocardial infarction or unstable angina occurred after withdrawal of diltiazem or placebo. The lack of difference in rebound after diltiazem or placebo withdrawal was consistent using paired and unpaired analyses. In conclusion, there appears to be no evidence that abrupt withdrawal of therapy with diltiazem results in rebound anginal symptoms.     

Pheochromocytoma presenting with Prinzmetal's angina

A patient with a pheochromocytoma presented with profound hypertension and the clinical syndrome of coronary artery spasm after the initiation of beta blockade therapy. It is postulated that intense unopposed alpha receptor stimulation can precipitate coronary artery spasm in susceptible persons with this tumor.     

Nifedipine therapy for stable angina pectoris: preliminary results of effects on angina frequency and treadmill exercise response.

Ten patients with stable angina pectoris secondary to atherosclerotic coronary artery disease received nifedipine (10 mg and 20 mg orally three times daily, each for 2 weeks) or placebo (for 2 weeks) in a single-blind manner during a 6 week period. One patient was excluded because nocturnal and resting angina developed while he was receiving placebo. The frequency of anginal attacks in the remaining nine patients decreased from 11.2 ± 2.2 (mean ± standard error of the mean) per patient per week during administration of placebo to 7.1 ± 1.6 during therapy with nifedipine at 10 mg and to 6.3 ±1.7 during administration of 20 mg of nifedipine (P < 0.05 for both doses of active drug versus placebo). Nitroglycerin consumption similarly decreased from 8.9 ± 2.3 tablets per patient per week (placebo) to 4.8 ± 1.4 tablets during administration of 10 mg of nifedipine and to 4.2 ± 1.2 during therapy with 20 mg of the drug (P < 0.05 for both doses of drug versus placebo). Duration of treadmill exercise increased from 368 ± 50 seconds (placebo) to 471 ± 72 seconds at the 10 mg dose of nifedipine and 522 ± 79 seconds at 20 mg (P < 0.05 for both doses versus placebo). Maximal S-T segment shift and product of heart rate × systolic blood pressure did not differ between the placebo period and that of active drug therapy. Treadmill exercise performed during subsequent double-blind, randomized crossover treatment with placebo and nifedipine revealed increased exercise duration after nifedipine therapy (524 ± 49 seconds) compared with that after placebo (462 ± 52 seconds) (P < 0.005) but, again, maximal S-T shift and the product of heart rate × systolic blood pressure did not differ. Side effects from nifedipine were minor and easily tolerable. The results seem to indicate that nifedipine prolongs exercise time by decreasing heart rate × systolic blood pressure product at a given work load, possibly in a manner similar to that of long-acting nitrate therapy.