Double-blind, randomized, placebo-controlled comparison of propranolol and verapamil in the treatment of patients with stable angina pectoris.

This study was performed to compare the relative efficacies of propranolol and verapamil in patients with stable angina pectoris. In 18 patients (16 men, two women, mean age 58 years) with coronary artery disease and angina of effort, the results of low (40 mg every 6 hours) and high-dose (80 mg every 6 hours) propranolol therapy were compared to those of low (80 mg every 6 hours) and high-dose (120 mg every 6 hours) verapamil therapy in a double-blind, randomized, placebo-controlled evaluation which lasted eight weeks: two weeks of placebo therapy, two weeks of propranolol or verapamil (one week low-dose, one week high-dose) therapy, three days of down-titration followed by one week of placebo therapy, two weeks of propranolol or verapamil therapy (whichever was not given earlier in the trial) (one week low-dose, one week hgh-dose) and three days of down-titration. During each period the following were quantitated: (1) chest pains/week; (2) nitroglycerin used/week; (3) transient ischemic S-T segment deviations and highest grade of ventricular ectopic activity on two-channel Holter monitor; (4) S-T segment deviations during supine bicycle exercise; (5) left ventricular volumes and ejection fraction at rest and during exercise (assessed by equilibrium gated blood pool scintigraphy); and (6) pulmonary function studies. Propranolol and high-dose verapamil therapy significantly reduced the frequency of angina, and high-dose verapamil therapy diminished both the need for nitroglycerin and the frequency of transient ischemic S-T segment deviations on Holter monitor. Neither agent exerted a clinically-important deleterious influence on left ventricular volumes or the ejection fraction. Forced vital capacity and forced expiratory volume were worsened by propranolol but not by verapamil. Thus, in the patient with angina of effort, verapamil is a satisfactory therapeutic alternative to propranolol.

Ergonovine provocation to assess efficacy of long-term therapy with calcium antagonists in Prinzmetal's variant angina.

In the patient with Prinzmetal's variant angina, the response to therapy with calcium antagonists may be assessed symptomatically, electrocardiographically (that is, by ambulatory electrocardiographic monitoring), or by response to ergonovine provocation. Although some studies have suggested a good relation between anginal frequency and ergonovine responsiveness in these patients, none has compared ambulatory electrocardiographic activity with the results of ergonovine provocation during the long-term administration of calcium antagonists. Therefore, the present study was performed to compare ergonovine responsiveness with both clinical and ambulatory electrocardiographic activity in patients with Prinzmetal's variant angina during long-term therapy with placebo, verapamil, and nifedipine. Accordingly, 27 patients with variant angina (19 men and 8 women, mean age 52 years) received placebo and verapamil for 2 months each, after which 23 of the 27 also received nifedipine for 2 months. All patients kept a diary of chest pains, and all had weekly 24-hour 2-channel ambulatory electrocardiographic (Holter) monitoring, from which episodes of transient S-T segment deviation were quantitated. During the final week of therapy with each agent, ergonovine was administered, beginning at 0.025 mg and incrementally increasing to 0.20 mg. It was discontinued when the patient had chest pain with S-T segment elevation greater than or equal to 0.1 mV or received a total dose of 0.50 mg. Of the 74 tests, 59 were negative; 6 of the negative tests occurred during a treatment period in which the patient had greater than 10 chest pains/week and greater than 25 episodes of S-T segment deviation/week. Of the 15 positive tests, 8 became positive during administration of less than 0.20 mg ergonovine; 5 of the positive tests occurred during a treatment period in which the patient had no chest pain or S-T segment deviation. Thus, in patients with variant angina, disease activity cannot be monitored reliably by ergonovine provocation because some patients have negative ergonovine tests at a time of marked clinical and electrocardiographic activity, whereas others have positive tests at a time of little (or no) disease activity.

Verapamil therapy for Prinzmetal's variant angina: comparison with placebo and nifedipine.

This study was performed (1) to assess the efficacy and safety of verapamil in patients with variant angina, and (2) to compare verapamil and nifedipine in patients with this clinical syndrome. In 27 patients, placebo and verapamil were administered in a long-term randomized, and double-blind study of 9 months' duration. In comparison to placebo, verapamil reduced the frequency of angina, nitroglycerin usage, transient episodes of electrocardiographic S-T segment deviation (as assessed by 2-channel Holter monitoring), and hospitalizations required for clinical instability. Subsequently, 23 patients were treated with nifedipine in a nonblind fashion for 2 months, and this agent exerted a beneficial effect similar to that of verapamil. Finally, gated equilibrium blood pool scintigraphy, performed in 10 patients at rest and during exercise during treatment with placebo, verapamil, and nifedipine, demonstrated that neither calcium antagonist caused a deterioration of left ventricular performance. Thus, (1) long-term oral verapamil and nifedipine are each superior to placebo and are of similar efficacy in patients with variant angina, and (2) neither agent adversely influences left ventricular performance in patients with relatively normal left ventricular function.

Effect of verapamil and nifedipine on left ventricular function at rest and during exercise in patients with Prinzmetal's variant angina pectoris.

To assess the effects of verapamil and nifedipine on left ventricular function at rest and during exercise in patients with Prinzmetal's variant angina pectoris, 10 patients (6 men and 4 women with a mean age of 52 years) with variant angina were each treated for 2 months periods with placebo, verapamil (400 +/- 80 mg/day, mean +/- standard deviation [SD]) and nifedipine (82 +/- 31 mg/day). During the final week of each 2 month treatment period equilibrium gated blood pool scintigraphy was performed at rest and during exercise. At rest, heart rate during verapamil therapy was lower than during treatment with nifedipine; systolic blood pressure and left ventricular volumes and ejection fraction were similar for the three interventions. The maximal work load achieved was similar during placebo, verapamil and nifedipine therapy. At the maximal work load common to all three exercise studies, heart rate and systolic blood pressure were lower with verapamil than with placebo and nifedipine; ventricular volumes and ejection fraction were similar with the three agents. Thus, in patients with variant angina and a wide range of left ventricular function at rest, neither verapamil nor nifedipine significantly alters left ventricular volumes or ejection fraction at rest or during exercise.

A controlled trial of verapamil for Prinzmetal's variant angina.

To assess the efficacy and safety of verapamil in variant angina pectoris, we entered 16 patients in a double-blind, randomized trial of nine months, duration. During treatment with verapamil, the frequency of angina fell substantially (12.6 +/- 25.9 chest pains per week with placebo, 1.7 +/- 2.8 pains per week with verapamil, mean +/- S.D.; P less than 0.01), as did the use of nitroglycerin tablets (14.4 +/- 34.4 tablets per week with placebo, 2.1 +/- 3.3 tablets per week with verapamil; P less than 0.05). The number of hospitalizations for clinical instability was significantly lower with verapamil (P less than 0.01). The number of episodes of transient ST-segment deviation during treatment with verapamil was reduced (33.1 +/- 39.3 ST-segment deviations per week with placebo, 7.7 +/- 11.7 deviations per week with verapamil; P less than 0.01). Verapamil caused no side effects forcing a reduction in dosage or a discontinuation. We conclude that verapamil is safe and effective in the therapy of variant angina pectoris.

Verapamil administration in variant angina pectoris. Efficacy shown by ecg monitoring.

Six patients with Prinzmetal's variant angina were treated with oral verapamil administration. Before and after the initiation of therapy, ambulatory ECG monitoring was performed to assess objectively the response to therapy. With verapamil administration, the frequency of both chest pain and transient ST-segment deviations was sharply diminished.

Verapamil for unstable angina at rest: a short-term randomized, double-blind study.

To assess the efficacy of verapamil in individuals with unstable angina at rest, 11 patients (five men and six women, average age 55 years) with recurrent chest pain at rest and transient ST segment deviation (elevation or depression greater than or equal to 0.1 mV) on continuous ECG monitoring were enrolled in a 3-day double-blind, randomized study. The day before randomization (day 1), all received single-blind placebo. On day 2 they were randomized to placebo (n = 6) or verapamil, 320 mg per day (n = 5). On placebo, the number of chest pains (day 1, 2.8 +/- 2.1; day 2, 2.2 +/- 2.5; NS), nitroglycerin used (day 1, 2.7 +/- 4.4 tablets; day 2, 2.2 +/- 3.5 tablets; NS), and ST segment deviations (day 1, 8.5 +/- 5.9; day 2, 5.3 +/- 7.1; NS) did not change. On verapamil, the number of chest pains (day 1, 5.4 +/- 2.2; day 2, 1.6 +/- 2.1; p less than 0.01), nitroglycerin used (day 1, 5.0 +/- 4.5 tablets; day 2, 1.6 +/- 2.6 tablets; p = 0.057), and ST segment deviations (day 1, 12.6 +/- 4.7; day 2, 6.2 +/- 6.2; p less than 0.05) fell. Since five of six placebo patients had frequent chest pain and ST segment deviations on day 2, they were changed blindly to verapamil, 320 mg per day. Of the five verapamil patients, three had no chest pain or ST segment deviations on day 2, but two had continued chest pain and ST segment deviations and were increased blindly to 480 mg verapamil per day. Of the eight patients given verapamil (320 mg per day) on day 3, five had chest pain or ST segment deviations and were increased blindly to 480 mg verapamil per day on day 4. Of the seven who received 480 mg verapamil per day on day 4, three had chest pain and ST segment deviations similar in frequency to that occurring on day 1. Thus in patients with unstable angina at rest, verapamil exerts an initial beneficial effect, but in some individuals this salutary influence is not sustained.

Concomitant calcium antagonist plus isosorbide dinitrate therapy for markedly active variant angina.

The present study was performed to assess the efficacy of concomitant calcium antagonist/isosorbide dinitrate therapy in patients with frequent episodes of variant angina and to compare such combination therapy with isosorbide dinitrate alone. We enrolled nine such patients (six men and three women, aged 47 +/- 9 [mean +/- standard deviation] years) in a long-term comparison of (1) oral isosorbide dinitrate (117 +/- 63 mg per day) alone, (2) verapamil (453 +/- 75 mg per day) + isosorbide dinitrate (given in the same dose as stated above), and (3) nifedipine (71 +/- 14 mg per day) + isosorbide dinitrate (also given in the same dose as stated), each administered for 2 months. During isosorbide dinitrate therapy, these nine patients averaged 23.7 +/- 37.3 chest pains per week, consumed 24.4 +/- 47.4 sublingual nitroglycerin tablets per week, and demonstrated 46.5 +/- 43.2 episodes per week of transient ST segment deviations on calibrated two-channel Holter monitoring. During therapy with verapamil/isosorbide dinitrate and nifedipine/isosorbide dinitrate, the frequency of angina and ST segment deviations was dramatically reduced (verapamil/isosorbide dinitrate, 3.9 +/- 3.6 chest pains per week and 3.5 +/- 2.6 ST segment deviations per week, p less than 0.05; nifedipine/isosorbide dinitrate, 3.1 +/- 4.0 chest pains per week and 5.5 +/- 6.6 ST segment deviations per week, p less than 0.05). In all respects, verapamil/isosorbide dinitrate and nifedipine/isosorbide dinitrate were similar to one another.(ABSTRACT TRUNCATED AT 250 WORDS)

Oral verapamil for paroxysmal supraventricular tachycardia: a long-term, double-blind randomized trial.

The effectiveness and safety of orally administered verapamil was tested in 11 patients with frequent paroxysmal supraventricular tachycardia. In a 4-month randomized, double-blind, placebo-controlled trial, the frequency of paroxysmal supraventricular tachycardia fell from 0.3 +/- 0.3 (mean +/- SD) to 0.1 +/- 0.1 episodes per day by patient diary (p less than 0.05) and from 0.7 +/- 0.7 to 0.3 +/- 0.5 episodes per day by Holter monitor (p less than 0.05) for placebo and verapamil treatment periods, respectively. Verapamil caused a decrease in the duration of paroxysmal supraventricular tachycardia (in minutes per day): placebo 27 +/- 51 by dairy, 67 +/- 111 by Holter; verapamil, 3 +/- 3 by diary, 1 +/- 2 by Holter (p less than 0.05). Five patients required a total of 35 pharmacologic cardioversions for sustained tachycardia: two during verapamil and 33 during placebo (p less than 0.001). No verapamil treatment period was shortened due to unacceptable paroxysmal supraventricular tachycardia, but five of 22 placebo treatment periods were shortened (p equal to 0.02). Verapamil was well-tolerated, causing mild constipation in five patients and headache in one. Oral verapamil is both safe and effective in the long-term treatment of patients with paroxysmal supraventricular tachycardia.

Ventricular ectopic activity with spontaneous variant angina: frequency and relation to transient ST segment deviation.

This study was performed (1) to assess the frequency of ventricular ectopic activity (ventricular bigeminy, couplets, or ventricular tachycardia) during spontaneous variant angina; (2) to assess the relation between ventricular ectopy and the severity and duration of ischemia; and (3) to evaluate the precise temporal relation between episodes of ischemia and ventricular ectopy. Fifteen ambulatory patients with variant angina (12 men, 3 women, aged 50 +/- 8 [mean +/- SD] years) had Holter monitoring for 24 hours/week for 10 months (total, 10,238 hours of monitoring), from which the following were measured during each episode of ST deviation (elevation or depression): duration of ST deviation (minutes), maximal ST deviation (millivolts), presence of ventricular ectopic activity, and timing of ventricular ectopy in relation to ST deviation. Of 645 episodes of ST deviation, 79 (12.2%) had associated ectopy, almost all of which occurred in three patients. The 79 episodes of ST deviation with ectopy lasted 4.6 +/- 3.3 minutes and averaged 0.16 +/- 0.12 mV, whereas the 566 episodes of ST deviation without ectopy lasted 4.7 +/- 6.1 minutes and averaged 0.17 +/- 0.11 mV (NS in comparison to the 79 episodes with ectopy). Of 489 episodes of ST elevation, 72 (14.7%) were accompanied by ventricular ectopy; of 156 episodes of ST depression, only seven (4.5%) had ectopy (chi 2 = 11.531, p less than 0.001). Of the 79 episodes of ventricular ectopy, almost all appeared during a period of increasing or maximal ST deviation, whereas only two appeared as ST deviation was resolving.(ABSTRACT TRUNCATED AT 250 WORDS)

Continuous electrocardiographic monitoring in patients with unstable angina pectoris: Identification of high-risk subgroup with severe coronary disease, variant angina, and/or impaired early prognosis.

We assessed the value of two-channel Holter monitoring during the initial hours of hospitalization in patients with unstable angina pectoris (UAP) to identify those with severe coronary artery disease (CAD), variant angina, and/or poor prognosis over the next 3 months. Accordingly, 116 UAP patients had Holter monitoring for 27 +/- 7 (mean +/- SD) (range 12 to 50) hours following hospitalization. Of these, 24 evolved myocardial infarction (MI) during monitoring and 92 did not. Transient ST segment alterations occurred in 21 of the 92. Of these 21, 4 had variant angina, were treated with calcium antagonists, and did well. Each of the remaining 17 had severe fixed CAD (left main or three-vessel) (n = 12) and/or poor prognosis over the 3 months after discharge as manifested by death (n = 1), MI (n = 3), and/or severe angina (n = 3). In contrast, 71 patients did not demonstrate transient ST segment alterations: none had variant angina (p less than 0.001), nine had left main or three-vessel CAD (p less than 0.001), and 50 were alive and well 3 months after discharge (p less than 0.001). Ventricular tachycardia (VT) was demonstrated by Holter monitor in 5 of the 92 patients: four had three-vessel CAD and the other had severe persistent angina. Thus in patients hospitalized with unstable angina, transient ST segment alterations and/or VT on Holter monitor are specific predictors of "high-risk" subgroup UAP patients with left main or three-vessel CAD, variant angina, and/or impaired 3-month prognosis.