Comparison of antianginal efficacies and exercise hemodynamic effects of nifedipine and diltiazem in stable angina pectoris

The antianginal efficacies of nifedipine (40 to 120 mg/day) and diltiazem (120 to 360 mg/day) were studied in 21 normotensive patients with chronic stable angina pectoris, using a randomized, double-blind, crossover design. Patients received each agent titrated to maximum tolerated doses for 6 weeks, after a 2-week placebo baseline period. The maximum tolerated dose for nifedipine was 72 +/- 8 (standard error) mg/day and for diltiazem 297 +/- 20 mg/day. Two patients discontinued nifedipine early because of side effects. Duration of symptom-limited treadmill exercise was longer during the nifedipine (556 +/- 43 seconds) and diltiazem periods (546 +/- 39 seconds) compared with placebo baseline (474 +/- 41 seconds, p less than 0.02). Compared with placebo, nifedipine caused a significant increase in heart rate both at rest standing and at peak exercise. Nifedipine decreased resting systolic blood pressure but had no effect at peak exercise. In contrast, diltiazem caused a significant decrease in heart rate at rest but had no effect on blood pressure at rest or at peak exercise. Thus, nifedipine and diltiazem have differential effects on heart rate and systolic blood pressure suggesting different modes of action. However, despite the increase in exercise duration, neither nifedipine nor diltiazem increased the heart rate-systolic pressure product during maximum exercise. This suggests that the antianginal effects of the 2 agents probably are mediated via reduction of myocardial oxygen demand at submaximal exercise. In addition, diltiazem appears to be better tolerated than nifedipine.     

Combination therapy with diltiazem and nifedipine in patients with effort angina pectoris

The antianginal effects of diltiazem and nifedipine alone and in combination were evaluated in a double-blind, randomized, placebo-controlled trial in 11 patients (nine men and two women, 57 +/- 8 years old) with stable effort angina. Each patient received placebo, 30 mg of diltiazem, 10 mg of nifedipine, and 30 mg of diltiazem plus 10 mg of nifedipine four times daily for 1 week each. Antianginal efficacy was assessed by means of a treadmill exercise test. The exercise tolerance time was significantly prolonged from 235.1 +/- 52 (placebo period) to 342.2 +/- 101 sec by diltiazem (p less than .01) and to 325.6 +/- 73 sec by nifedipine (p less than .01). The drug combination further prolonged exercise time to 451.1 +/- 103 sec, which was significantly longer than the interval attained with either diltiazem (p less than .01) or nifedipine (p less than .01) alone. The plasma concentration of diltiazem was unaffected by the addition of nifedipine, whereas the plasma nifedipine concentration was significantly increased from 34.8 +/- 11 to 106.4 +/- 37 ng/ml (p less than .001) by the concomitant administration of diltiazem. These data suggest that exercise tolerance in patients with effort angina is increased by the concomitant administration of diltiazem and nifedipine associated with an increase in the nifedipine plasma concentration.     

Calcium-channel blockers for combined angina pectoris and systemic hypertension

Calcium-channel blockers have been successfully used in the treatment of angina of effort and systemic hypertension. Many patients present with concomitant angina pectoris and hypertension. Controlled clinical trials demonstrate that the calcium-channel blockers are safe and effective as monotherapy in the treatment of these patients, and that their use compares favorably with that of propranolol. The effectiveness of these agents in hypertension appears to be primarily due to their ability to induce systemic vasodilation. Calcium-channel blockers have several therapeutic effects in angina pectoris. Beneficial actions on the major determinants of oxygen consumption, i.e. heart rate, blood pressure and contractility, are generally seen. The potent coronary vasodilating actions of these agents allow for increased coronary blood flow. Improvements in ventricular compliance, regression of left ventricular hypertrophy and cardioprotection appear to be additional effects of the calcium-channel blockers; their contribution to the drugs' overall therapeutic efficacy is presently being evaluated. Calcium-channel blockers are a welcome addition to drug regimens available for the management of patients with coexisting angina pectoris and hypertension.     

Comparison of atenolol and nifedipine in chronic stable angina pectoris

The antiangina effects of atenolol, 50 to 200 mg once daily, or nifedipine, 10 to 30 mg 3 times daily, were evaluated in a multicenter, randomized, double-blind, parallel study of 39 patients with known symptomatic coronary artery disease. Treatment was titrated to produce at least a 30% increase in treadmill exercise duration over placebo baseline and then maintained at that dosage for an additional 3 weeks. Both treatments produced significant (p less than 0.001) increases in duration of exercise, total work and exercise capacity when compared with placebo baseline. These improvements in exercise performance were obtained with significant (p less than 0.001) reductions in both ST-segment depression and rate-pressure product for atenolol compared with nifedipine. Furthermore, the total angina attack rate and rate at rest were significantly (p less than 0.01) less frequent with atenolol than with nifedipine. Hence, the antiischemic effects of atenolol exceeded those of nifedipine, based on ST-segment depression and rate-pressure product at comparable workloads.     

Comparison of hydrochlorothiazide and sustained-release diltiazem for mild-to-moderate systemic hypertension

The safety and efficacy of sustained-release diltiazem, 120 to 180 mg twice daily, was compared with those of hydrochlorothiazide, 25 to 50 mg twice daily, in 207 patients with mild-to-moderate hypertension (supine diastolic blood pressure [BP] 95 to 114 mm Hg) using a baseline, placebo, parallel-design study protocol. All patients received placebo for 2 to 4 weeks, followed by either study drug during the double-blind phase, titrated over 8 weeks to achieve a goal of supine diastolic BP reduction of at least 10 mm Hg and/or a diastolic BP of less than 90 mm Hg. Patients not achieving the treatment goal with either drug alone received the other drug in combination. Both drugs produced significant decreases in supine and upright BP throughout the 26-week study. The magnitude of decrease in mean supine diastolic BP was similar for both drugs as monotherapy at week 14 (-11.4 and -12.1 mm Hg, respectively). Hydrochlorothiazide produced significantly greater reductions at week 14 in mean supine systolic BP than sustained-release diltiazem (-19.5 and -12.7 mm Hg, respectively). The difference in mean supine diastolic BP reduction with the 2 drugs diminished when hydrochlorothiazide (50 mg/day) was compared with sustained-release diltiazem. The BP effects were sustained for 6 months with both drugs. The 2 drugs appeared to lower BP more in patients older than 60 years and more in black than in white patients. The combination of the 2 drugs decreased supine diastolic BP to goal levels in about 56% of the patients not achieving goal with either drug alone. Adverse effects were minimal with either drug alone and in combination, except for hypokalemia, which increased with thiazide alone and in combination.     

Usefulness of sustained-release diltiazem for stable angina pectoris

Sustained-release diltiazem, 120 and 180 mg twice daily, was assessed in a multicenter, double-blind, randomized, placebo-controlled trial in 65 stable angina patients with exercise-induced ST depression. Exercise testing was performed 12 +/- 1 hours after the last dose at the end of each of the 3 treatment weeks. Both dose levels of drug reduced spontaneous angina (p less than 0.001) and increased exercise duration (p less than 0.01) and time to 1-mm ST depression (p less than 0.001). No differences were noted between the 2 dose levels. Rate-pressure product at maximal exercise was similar for the 3 groups. Only 1 patient terminated the study because of adverse drug effects; severe adverse effects occurred in 1 placebo and 1 low-dose period. Sustained-release diltiazem is safe and efficacious monotherapy for patients with stable angina.     

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.     

Comparison of acute hemodynamic effects of nitroglycerin versus diltiazem and combined acute effects of both drugs in angina pectoris

Fifteen patients with exertional angina underwent hemodynamic monitoring and measurement of cardiac output during a control treadmill exercise test. They were then randomized to receive sustained-release nitroglycerin, 13 mg (group I) or placebo (group II). Repeat exercise testing revealed that in group I, both maximal oxygen consumption and cardiac output increased significantly. In group II neither maximal oxygen consumption nor cardiac output increased significantly. All patients then received diltiazem, 60 mg, and repeat testing was carried out 1 hour later. In group I maximal oxygen consumption and cardiac output were higher than control, but were no higher than after nitroglycerin. In group II, maximal oxygen consumption increased significantly, but the increase in cardiac output was not significant. Thus, sustained-release nitroglycerin, 13 mg, or diltiazem, 60 mg, both improve exercise performance, but the combination does not improve exercise performance to an extent greater than either drug alone.     

Effects of diltiazem during tachycardia-induced angina pectoris

To investigate the mechanism of relief of angina pectoris by diltiazem administration, 14 patients with effort angina were studied using a protocol to control heart rate. Coronary, systemic and left ventricular (LV) hemodynamic function was assessed at rest and during tachycardia stress (atrial pacing)-induced angina before and during diltiazem infusion. Angina occurred in all patients during tachycardia stress before diltiazem administration. During tachycardia stress at the heart rate that produced angina after diltiazem infusion, pressure-rate product, coronary sinus flow and resistance and ST-segment depression were all similar to findings before diltiazem. Although at the onset of angina, systolic pressure was usually slightly lower after diltiazem infusion (138 +/- 11 vs 128 +/- 11 mm Hg, p less than 0.05), the pacing rate at onset of angina was higher in only 3 patients and the pressure-rate product was higher in only 1 patient. After diltiazem, left ventricular end-diastolic pressure increased less frequently after interruption of pacing. The results suggest that diltiazem favorably alters the relation between myocardial oxygen demand and supply at rest, but during tachycardia, anginal threshold and coronary reserve do not change. Diltiazem's potent antianginal action, shown in previous investigations using exercise-induced angina, is not prominent when heart rate is controlled. The major benefit of diltiazem in patients with stress-induced angina is related to reduction of myocardial oxygen demand rather than improved myocardial oxygen delivery.     

Superiority of combined diltiazem and propranolol therapy for angina pectoris

Twenty-four patients with stable angina were evaluated in a 14 week crossover trial. A single-blind placebo period (baseline 1) was followed by two double-blind periods evaluating maximum tolerated doses of diltiazem (up to 360 mg daily) vs placebo. Over the next 1 to 4 weeks, propranolol was started and increased until clinically documented beta-blockade was achieved (baseline 2). The final phase consisted of a pair of evaluation periods comparing propranolol plus the maximum tolerated dose of diltiazem to propranolol and placebo. The daily rate of angina attack was 1.6 during baseline, was unchanged during placebo therapy, but fell during treatment with diltiazem to 0.6 (p less than .005). With the addition of diltiazem to propranolol, the angina rate was improved (0.3) compared with that with either propranolol alone (0.6) or propranolol and placebo (0.5) (p less than .01). Total exercise duration during baseline 1 was 360 sec and increased to 497 sec with diltiazem, 481 sec with propranolol, and 527 sec with the combination of diltiazem and propranolol. Two patients with reduced ejection fractions developed congestive heart failure with propranolol. The combination of diltiazem and propranolol similarly resulted in congestive heart failure in one patient who had tolerated both drugs alone.     

Comparison of combination nifedipine-propranolol and diltiazem-propranolol with high dose diltiazem monotherapy for stable angina pectoris

Patients with chronic stable angina are frequently treated with calcium antagonist-beta-blocker combination drug therapy. However, there is a paucity of data comparing such combination therapies with each other and with high dose calcium antagonist monotherapy. Nineteen patients with chronic stable angina pectoris were studied using a prospective, randomized, Latin-square crossover protocol in an effort to determine the differential effects of nifedipine-propranolol combination therapy, diltiazem-propranolol combination therapy and high dose diltiazem monotherapy on exercise treadmill performance. All patients performed exercise tolerance tests after 4 weeks on each of the 3 therapeutic regimens. Both nifedipine (mean daily dose 70 +/- 23 mg) and diltiazem (mean daily dose 237 +/- 12 mg) in combination with propranolol (mean daily dose 146 +/- 58 mg) resulted in significant increases in total exercise time, time to onset of angina and time to maximal ST-segment depression compared with high dose diltiazem (mean daily dose 347 +/- 38 mg) monotherapy (p less than or equal to 0.001). Double-product at rest and the increase observed from rest to the end of stage 1 were significantly decreased during nifedipine-propranolol and diltiazem-propranolol combination therapy compared with high dose diltiazem monotherapy (p less than or equal to 0.001). In patients with chronic stable angina both nifedipine-propranolol and diltiazem-propranolol combination therapy resulted in significantly greater improvement in exercise performance compared with high dose diltiazem monotherapy.     

Comparison of diltiazem at two dose levels with propranolol for treatment of stable angina pectoris

Two dose levels of diltiazem with propranolol were compared in the management of chronic stable angina. Two groups of patients were treated for alternate periods of 4 weeks with each drug in a double-blind crossover with computer-assisted maximal treadmill tests and ambulatory ST-segment monitoring for evaluation of efficacy and safety. In 12 patients who received diltiazem, 180 mg/day, the time to development of angina increased from 5.9 +/- 0.7 minutes (+/- standard error of the mean) during placebo treatment to 8.3 +/- 0.8 minutes during diltiazem treatment and to 9.2 +/- 0.8 minutes with propranolol, 240 mg/day. Three patients became angina-free when they were treated with both drugs. Among 12 patients who received diltiazem, 360 mg/day, 1 patient became angina-free during treatment with both drugs and 1 became angina-free with diltiazem only. The mean exercise time increased from 5.8 +/- 0.7 minutes with placebo to 8.6 +/- 1.0 minutes with diltiazem, 360 mg/day, and to 8.2 +/- 0.6 minutes with propranolol, 240 mg/day. Analysis of variance showed no difference in efficacy between the 2 doses of diltiazem or between the 2 drugs. Ambulatory heart rate was reduced both during the day and at night with both drugs and significantly more with propranolol than with diltiazem treatment. Except for 1 patient in whom a rash developed when given diltiazem, 180 mg/day, and another who had both a rash and first-degree heart block with diltiazem, 360 mg/day, both drugs were well tolerated. Thus, diltiazem in a daily dose of 180 or 360 mg/day is as effective as propranolol for the treatment of chronic stable angina.     

Sustained-release diltiazem versus metoprolol in stable angina pectoris

The efficacy of sustained-release diltiazem (diltiazem-SR) 120 mg b.i.d. was compared with metoprolol 100 mg b.i.d. in 12 patients with stable angina. Following a 1-week placebo period, patients received diltiazem-SR or metoprolol in two 3-week treatment periods, in a randomized double-blind crossover design. Total exercise time was increased more with diltiazem-SR than with metoprolol (1.2 min vs 0.4 min, P = 0.02), although the reduction in frequency of weekly anginal attacks was equal with both drugs (5 +/- 3 with placebo to 1 +/- 1 with both drugs). The difference between diltiazem-SR and metoprolol may, in part, be due to the fact that the tests were performed 12 h after drug administration. The diltiazem plasma levels were in the therapeutic range; metoprolol plasma levels, in contrast, were all below the therapeutic range. In addition, the patients might be tired out earlier during beta-blockade therapy, because a greater increase in exercise time with diltiazem-SR compared with metoprolol was found in those patients in whom the exercise endpoint changed from angina to fatigue. Thus, diltiazem-SR effectively reduces the frequency of anginal attacks when given twice daily, and improves exercise capacity to a greater extent than metoprolol 12 h after last dose.     

Comparison of effects of nisoldipine-extended release and amlodipine in patients with systemic hypertension and chronic stable angina pectoris

The efficacy and safety of nisoldipine-extended release (ER) and amlodipine were compared in a 6-week multicenter, randomized, double-blind, double-dummy, parallel group, titration-to-effect trial in patients with stage 1 to 2 systemic hypertension (90 to 109 mm Hg diastolic blood pressure [BP]) and chronic stable angina pectoris. After a 3-week placebo run-in period, patients (n = 120) were randomly assigned to active treatment with either nisoldipine-ER (20 to 40 mg) or amlodipine (5 to 10 mg) once daily, titrated as necessary after 2 weeks to achieve diastolic BP <90 mm Hg. After 6 weeks, the mean reduction in systolic/diastolic BP from baseline was 15/13 mm Hg with nisoldipine-ER and 13/11 mm Hg with amlodipine (p = NS/p = NS). Both drugs resulted in similar BP responder rates (diastolic BP <90 mm Hg in 87% of patients who received nisoldipine-ER and 78% of patients on amlodipine, p = NS) and anti-ischemic responder rates (increasing exercise time >20% in 20% and 27%, respectively [p = NS], and increasing exercise time >60 seconds in 32% and 29% of patients, respectively [p = NS]. Also, after 6 weeks of active therapy, there was a similar mean increase in total exercise duration (23 seconds in the nisoldipine-ER group and 21 seconds in the amlodipine group, p = NS). Neither drug increased heart rate and both decreased frequency of anginal episodes. Adverse events were infrequent, and typically were vasodilator-related effects (including headache and peripheral edema) that occurred with somewhat higher incidence in the nisoldipine-ER group. Thus, nisoldipine-ER and amlodipine provided comparable antihypertensive and anti-ischemic efficacy, and both were generally well tolerated.     

Comparison of oral propranolol and verapamil for combined systemic hypertension and angina pectoris. A placebo-controlled double-blind randomized crossover trial

The relative efficacies of oral verapamil, a calcium-entry blocking drug, and propranolol, a beta-adrenergic blocking drug, were compared in 12 patients who had both stable angina pectoris and mild to moderate systemic hypertension, using a placebo-controlled, double-blind, randomized crossover protocol. Compared with placebo, both propranolol and verapamil decreased the frequency of anginal attacks and the number of nitroglycerin tablets consumed, and increased exercise duration and total work; there were no significant differences in the antianginal effect of the two drugs. Both verapamil and propranolol reduced the supine and standing systolic and diastolic blood pressure measured at rest; compared with propranolol, however, verapamil had greater effects on standing diastolic blood pressure (p less than 0.002). Resting heart rate was reduced from placebo baseline with large doses of both drugs; compared with verapamil, however, propranolol exerted greater effects on resting heart rate and rate-pressure product. Plasma renin activity was increased from placebo baseline with verapamil (p less than 0.05), but was reduced with propranolol (p less than 0.05); no significant change in plasma aldosterone was seen with either drug. Verapamil appears to be a safe and effective treatment alternative to propranolol for relieving anginal symptoms, improving exercise tolerance, and reducing elevated systemic blood pressure in patients with both angina pectoris and mild to moderate systemic hypertension.     

Effects of diltiazem alone or with isosorbide dinitrate or with atenolol both acutely and chronically for stable angina pectoris

To establish the contribution of combination therapy in stable angina, the short- and long-term effects of diltiazem (120 mg and 360 mg/day, respectively), and the additive effects of sublingual isosorbide dinitrate, 10 mg, and atenolol, 100 mg, were studied in 11 patients with chronic stable angina using an open-label sequential design. All patients underwent exercise testing without therapy, and with each drug and their combinations. Exercise time and heart rate-blood pressure product were measured at 1-mm ST-segment depression, or at peak exercise if the test result was negative. Exercise time increased from a control value of 8.0 +/- 2.3 minutes (mean +/- standard deviation) to 11.4 +/- 2.4 minutes (p less than 0.0001) after the administration of isosorbide dinitrate, to 11.3 +/- 1.8 minutes (p less than 0.001) after short-term diltiazem and to 12.4 +/- 1.5 minutes (p less than 0.001) after long-term diltiazem. The rate-pressure product increased from a control value of 19,070 +/- 3,564 to 24,431 +/- 4,795 beats/min X mm Hg (p less than 0.0001) after isosorbide dinitrate, to 22,287 +/- 4,753 beats/min X mm Hg (p less than 0.01) after short-term diltiazem and to 21,812 +/- 3,976 beats/min X mm Hg (p less than 0.007) after long-term diltiazem. The addition of atenolol to long-term diltiazem significantly reduced the rate-pressure product compared with long-term diltiazem alone (21,812 +/- 3,976 vs 13,926 +/- 2,880 beats/min X mm Hg, (p less than 0.002), although there was no further significant increase in exercise time (12.4 +/- 1.5 vs 13.3 +/- 1.6 minutes).(ABSTRACT TRUNCATED AT 250 WORDS)     

Efficacy and safety of sustained-release diltiazem in stable angina pectoris

The safety and efficacy of a sustained-release preparation of diltiazem (diltiazem-SR), with dose levels of 240 and 360 mg/day, were assessed in 18 patients with stable angina of effort. A double-blind, placebo-controlled, randomized, crossover protocol was used. Diltiazem-SR, when given twice daily, reduced the frequency of weekly anginal attacks from 9.3 +/- 10.4 with placebo to 3.7 +/- 4.7 with 240 mg/day and to 3.1 +/- 4.7 with 360 mg/day (both p less than 0.01 compared with placebo). Treadmill time was increased from 410 +/- 180 seconds during the placebo phase to 519 +/- 177 seconds during the 240-mg/day dose and to 506 +/- 182 seconds during the 360-mg/day dose of diltiazem-SR (both p less than 0.01 compared with placebo). The time to the onset of angina and ischemic ST-segment depression were similarly prolonged by both doses of diltiazem-SR. The beneficial effects of diltiazem-SR appeared partly due to a reduction in the heart rate during submaximal exercise. Diltiazem-SR is effective and safe for the treatment of angina of effort when given twice daily.     

A randomized double-blind comparison of diltiazem and nifedipine in stable angina

A double-blind crossover trial comparing diltiazem (360 mg/day) and nifedipine (120 mg/day) for treatment of stable angina was conducted in 21 of 27 patients with proven coronary artery disease who completed the trial. All patients started with a 2 week placebo period followed by a random assignment to either drug treatment for 3 weeks and subsequent crossover to the other treatment. The two drug treatment periods were separated by a 1 week placebo washout phase and the study was completed with a 1 week placebo phase. There were no significant differences between patients' responses to diltiazem and nifedipine in relation to time to onset of angina, ST depression responses to exercise, heart rate or systolic or diastolic blood pressure. A total of 37 adverse effects were reported with nifedipine compared with 9 with diltiazem in the 22 patients in whom drug safety was analyzed. Additionally, two patients treated with nifedipine were withdrawn from study participation before crossover. There was a significant (p less than 0.05) difference with respect to incidence of edema (7 of 22 patients taking nifedipine, 1 of 22 taking diltiazem) and dizziness (7 of 22 patients taking nifedipine, 0 of 22 taking diltiazem). The most frequent adverse effect reported with diltiazem was rash (3 of 22 patients). Severe adverse effects were reported in four patients: in one with diltiazem (rash) and in three with nifedipine (palpitation in two and headache in one). A reduction in prescribed dosage was required in 37% of nifedipine-treated compared with 6% of diltiazem-treated patients. Efficacy measures were significantly improved above placebo levels by both diltiazem and nifedipine.(ABSTRACT TRUNCATED AT 250 WORDS)     

Sustained-release verapamil and nifedipine in exercise-induced angina pectoris.

In a randomised, double-blind, crossover study of oral sustained-release verapamil 360 mg o.d. ('SR-verapamil') and oral nifedipine 20 mg t.d.s. in 19 patients with chronic stable angina pectoris, significantly greater improvement from baseline was seen with SR-verapamil than with nifedipine. Mean exercise duration was 380 +/- 108 s with SR-verapamil and 343 +/- 130 s with nifedipine (P less than 0.05); mean time to onset of angina was 326 +/- 79 s with SR-verapamil and 239 +/- 79 s with nifedipine (P less than 0.01); median time to 1 mm ST depression was 252 s (range 114-579) with SR-verapamil and 182 s (range 84-582) with nifedipine (P less than 0.01); mean ST depression at maximum exercise was 1.65 +/- 0.56 mm with SR-verapamil and 2.17 +/- 0.98 mm with nifedipine (P less than 0.05). Ambulatory ECG recordings indicated a trend in favour of SR-verapamil (median ST-time integral 0.00 [range 0-24.16] mm h-1 with SR-verapamil, 1.15 [range 0-12.50] mm h-1 with nifedipine, not significant). Median glyceryl trinitrate consumption was significantly lower (P less than 0.05) with SR-verapamil (0.21; range 0-1.25 per day) than with nifedipine (0.31; range 0-1.32 per day), but there was no significant difference between angina attack frequency. Adverse events were reported by two patients with SR-verapamil and nine with nifedipine. Once-daily sustained-release verapamil 360 mg has a significantly better effect on exercise tolerance than nifedipine 20 mg t.d.s. and also appears to be better-tolerated.