In a multicenter double-blind study, 227 patients with suspected acute myocardial infarction (AMI) were randomized within 12 hr from onset of symptoms to treatment with nifedipine (112 patients) or placebo (115 patients). AMI was confirmed in 74 patients on nifedipine and in 83 on placebo. Patients with AMI received nifedipine 5.5 +/- 2.9 hr (mean +/- SD) after onset of symptoms. Infarct size was assessed by the release of creatine kinase isoenzyme MB (CK-MB). Infarct size index (CK-MB geq/m2) was 25 +/- 16 (n = 71) in the nifedipine group and 23 +/- 13 (n = 77) in the placebo group (NS). After the first 10 mg of nifedipine systolic blood pressure fell from 147 +/- 30 to 135 +/- 28 mm Hg (p less than .01) and heart rate rose from 75 +/- 18 to 79 +/- 19 beats/min (p less than .01). No change was observed after the first placebo dose. The treatment was continued for 6 weeks. Over this period there were 10 deaths in each group. Early treatment with nifedipine in patients with AMI does not seem to reduce infarct size as determined by enzyme level.

The clinical effects of intravenous streptokinase in patients with acute myocardial infarction were compared with those of intracoronary streptokinase in a randomized, prospective study. Comparisons were also made with a historical control group. Fifty patients were entered into the study at 2.4 +/- 1.2 hr after onset of pain, and 27 were assigned to intravenous and 23 to intracoronary therapy. The doses of streptokinase averaged 212,000 U ic and 845,000 U iv (0.75 X 10(6) U/5 hr, n = 14 or 10(6) U/1 hr, n = 13). Results of studies of the two intravenous dosage schedules were similar and so were combined. Streptokinase was administered at 2.8 +/- 1.0 hr after onset of pain in the intravenous and at 4.3 +/- 1.4 hr in the intracoronary drug group (p less than .001). Convalescent (day 10) radionuclide ejection fractions were 54 +/- 14% for the intravenous and 50 +/- 16% for the intracoronary drug group. Change in ejection fraction from day 1 to 10 tended to be greater after intravenous drug: 5.1% (p less than .08) vs 1.2% (NS). Semiquantitative regional wall motion indexes in the infarct zone showed significant and similar modest improvement from admission to day 10 in both groups (p less than .02). Accelerated enzyme-release kinetics were noted after both therapies. Times of peak enzyme levels for patients on intravenous and intracoronary drug were, respectively, 12.5 +/- 5.0 and 11.5 +/- 4.3 hr for creatine kinase MB isoenzyme and 31.7 +/- 11.8 and 28.1 +/- 12.7 hr for lactic dehydrogenase (LDH). Peak LDH-1 level was lower in patients receiving intravenous drug than in the historical control group (p less than .05). Electrocardiographically summed ST segments diminished rapidly after therapy in both groups; Q wave development was similar and overall R wave loss was equivalent and less extensive compared with in historical control subjects. Infarct pain requiring morphine was diminished similarly in both treatment groups. Incidence of early arrhythmias and heart failure also did not differ. Posttherapy ischemic events and early surgery tended to be more common in the intracoronary group and bleeding was more common in the intravenous group. Intravenous drug did not decrease early hospital mortality (intravenous drug = 5, historical control = 4, intracoronary drug = 1); the differences in this parameter among groups were not significant. At convalescent angiographic evaluation, anterograde perfusion was present in 73% of those receiving intravenous and 76% of those receiving intracoronary drug.(ABSTRACT TRUNCATED AT 400 WORDS)

Forty-one patients undergoing coronary artery bypass grafting were randomly assigned to receive prophylactic timolol or placebo, given in a double-blind fashion. beta-Adrenoceptor-blocking therapy was stopped at least one half-life before surgery. Three to 7 hr after surgery (304 +/- 56 min), 0.5 mg of timolol or placebo was given intravenously twice daily in a double-blind manner. When oral medications were resumed postoperatively, 10 mg of timolol twice daily or placebo was continued orally. Continuous electrocardiograms were recorded for 24 hr before and for 7 days after surgery with a standard cassette recorder. No patient received digoxin. Both groups were comparable for frequency of preoperative supraventricular arrhythmias, left ventricular ejection fraction, duration of cardiopulmonary bypass, aortic cross-clamp time, number of bypass grafts, and total duration of monitoring. Analysis of arrhythmias was done by hand counts, and supraventricular arrhythmias were divided into supraventricular tachycardia and atrial fibrillation and/or flutter. Timolol decreased the frequency of supraventricular tachycardia (581 episodes placebo vs 84 timolol; p less than .05) and of atrial fibrillation and/or flutter (291 episodes placebo vs five timolol; p less than .05). Timolol decreased the number of patients with severe (heart rate greater than 200 beats/min, duration greater than 50 beats) episodes of supraventricular tachycardia (four placebo vs 0 timolol; p less than .05) and also decreased the number of episodes of severe (heart rate greater than 200 beats/min, duration greater than 5 min) atrial fibrillation and/or flutter (16 placebo vs one timolol; p less than .005). There were differences in the durations of supraventricular arrhythmias.(ABSTRACT TRUNCATED AT 250 WORDS)

Although unstable angina can be initially controlled with medical therapy in most patients, there is a high incidence of subsequent death, myocardial infarction, or need for coronary bypass surgery to control symptoms. Identification at the time of presentation of the patient likely to do poorly on continued medical therapy would be useful in advising consideration of surgical therapy. Since coronary arterial spasm may have a significant role in the pathophysiology of unstable angina in some patients, the recently developed calcium channel antagonists may therefore be of particular benefit in the medical therapy of unstable angina. One hundred thirty-eight patients were entered into a randomized double-blind study of the efficacy of adding nifedipine to conventional treatment of unstable angina (nitrates and beta-blockers) and were followed for 18 months. Of these patients, 104 underwent coronary arteriography. A multivariate Cox's hazard function analysis was applied to variables selected from the history, electrocardiographic (ECG) changes during chest pain, and from scintigraphic and coronary arteriographic data to determine those variables most predictive of response to medical therapy. The percentage of the left ventricular myocardium supplied by vessels with 70% or greater luminal stenosis was the most significant variable in influencing failure of medical therapy defined as sudden death, myocardial infarction, or need for bypass surgery. Whether or not the patient received nifedipine was the second most powerful variable, with the use of nifedipine reducing by half the relative risk of failing medical therapy. These were followed by cigarette smoking and presence of global ST segment changes during ischemia. After 18 months the nifedipine group had fewer patients failing medical therapy (p = .02), with fewer patients undergoing coronary bypass surgery (p less than .01). However, nifedipine did not appear to have a preventive effect against myocardial infarction or death. Kaplan-Meier actuarial curves confirmed that medical therapy was significantly less successful in the presence of increasing numbers of significantly stenotic vessels (p = .03). However, nifedipine provided a significant beneficial effect in patients with two or more stenotic vessels (p less than .01) and in whom 50% or more of the myocardium was supplied by vessels with 70% or greater stenosis (p = .01). Thus, although patients with advanced obstructive coronary disease have the greatest likelihood of unfavorable outcomes, the addition of nifedipine is of significant benefit.(ABSTRACT TRUNCATED AT 400 WORDS)

Nifedipine (10 mg qid) and captopril (25 mg qid) were tested alone and in combination in 14 patients suffering from severe primary hypertension. Each study period was of 1 week's duration. Circulatory response was evaluated through hourly pressure and pulse rate readings. The fall in pressure after oral nifedipine was maximal within 1 hr or less and was generally accompanied by palpitation and increase in pulse rate; with a six hourly dosing regimen the tendency of blood pressure to recover after each dose was interrupted by the next dose, so that values remained significantly reduced throughout the 24 hr, although pressure fluctuations were evident. Promptness of the antihypertensive action of captopril was similar, but the magnitude and the duration of the fall in pressure were less pronounced. When the converting-enzyme inhibitor was combined with the calcium-channel blocker, pressure fluctuations were not abolished, but the antihypertensive response was definitely enhanced, so that normal blood pressure was maintained for several hours during the day. Additional positive effects of captopril were mitigation of the heart rate reaction and prevention of the ankle pitting or edema elicited by nifedipine. A balance in arteriolar and venular dilatation promoted by captopril is the suggested mechanism for these effects. With the two-drug combination the function of the left ventricle was not reduced and possibly improved; blood urea nitrogen and serum electrolyte and creatinine concentration were not affected. Plasma renin activity increased with captopril and reverted toward baseline with the addition of nifedipine, suggesting an interference of the calcium-channel blocker with the release of renin.

A number of studies have shown short-term hemodynamic and symptomatic improvement in patients with congestive heart failure treated with angiotensin converting-enzyme inhibitors. The long-term efficacy of the oral long-acting converting-enzyme inhibitor enalapril remains to be established in controlled studies. We evaluated this drug in 36 patients with New York Heart Association functional class II to III heart failure who were clinically stable on digoxin and diuretic therapy. After baseline assessment of symptoms, exercise capacity, and results of echocardiographic examination and right heart catheterization, patients were randomly assigned to treatment with 5 mg enalapril twice daily (n = 18) or placebo (n = 18) in a double-blind fashion. The two groups had similar clinical, echocardiographic, and hemodynamic characteristics before treatment. After 3 months of treatment, the enalapril group showed a significant improvement as judged by subjective patient impression, functional class, and exercise duration (9.3 +/- 5.7 vs 17.6 +/- 5.6 min; p less than .001). Diuretic dosage was reduced in six patients and increased in one patient, one patient had died and another had been withdrawn from the study. In the placebo group there was no significant change with respect to patient impression, functional class, or exercise duration; diuretic dosage was increased in seven patients and four patients had died. Echocardiographic left ventricular dimensions were significantly reduced and left ventricular shortening fraction significantly increased in the enalapril group but were unchanged in the placebo group.(ABSTRACT TRUNCATED AT 250 WORDS)

One hundred and one patients with sustained unimorphic ventricular tachycardia underwent programmed ventricular stimulation with one of two protocols. Fifty patients underwent programmed stimulation with protocol A, which consisted of burst overdrive pacing, single, double, and triple extrastimuli at the right ventricular apex, right ventricular outflow tract, or septum, and then at the left ventricular apex. Fifty-one patients underwent programmed stimulation with protocol B, which consisted of burst overdrive pacing, single and double extrastimuli at the right ventricular apex, right ventricular outflow tract or septum, and at the left ventricular apex, followed by triple extrastimuli at these sites. The stimulation protocol was continued until sustained ventricular tachycardia or rapid, polymorphic ventricular tachycardia greater than 10 sec in duration was induced. With protocol A, clinical and nonclinical ventricular tachycardia was induced in 76% and 36% of patients, respectively; with protocol B, clinical and nonclinical ventricular tachycardia was induced in 85% and 38% of patients, respectively. Direct-current countershock for sustained polymorphic ventricular tachycardia was required in 10% of patients studied under protocol A, compared with in 2% of patients studied under protocol B. With protocol A, near-maximal yield of induced clinical (72%) and nonclinical ventricular tachycardia (30%) was attained after the use of triple extrastimuli at the first stimulation site. The yield of stimulation at a second right ventricular site and of left ventricular stimulation was only an additional 2% each. With protocol B, triple extrastimuli increased the yield of induced clinical ventricular tachycardia from 61% to 85%.(ABSTRACT TRUNCATED AT 250 WORDS)

Minoxidil, a potent predominant arterial dilator, improves hemodynamics over the short term in patients with heart failure. In random double-blind fashion 17 patients with chronic left heart failure were given minoxidil (nine patients) or placebo (eight patients) in addition to digoxin and diuretics for 3 months. Cardiac index and heart rate increased and mean arterial pressure and systemic vascular resistance fell within 4 hr of minoxidil administration. Right heart and pulmonary arterial pressures were unchanged over the short term but rose after long-term minoxidil. After 3 months of minoxidil treatment, systemic vascular resistance was still reduced (11.7 +/- 6.3[SD] vs 17.1 +/- 3.1 U at baseline; p less than .05). Hemodynamics were similar at baseline and remained unchanged during placebo treatment. Mean left ventricular ejection fraction rose from 29.6 +/- 17.7% to 42.7 +/- 22.3% (p less than .05) after 3 months of minoxidil treatment (this result was influenced largely by responses in two patients), and remained unchanged (at 25.1 +/- 16.6%) after 3 months of placebo. Exercise duration and maximal oxygen uptake during exercise were unchanged during minoxidil or placebo treatment. Total clinical events, including increased need for diuretics, angina, ventricular arrhythmias, worsening heart failure, and death were all more frequent during minoxidil vs placebo administration (21 vs seven total events; p less than .01). Thus, despite improving hemodynamics and left ventricular function, long-term minoxidil administration was associated with a poorer clinical course in patients with chronic left ventricular failure. Furthermore, this experience demonstrates that improvement of left ventricular function alone cannot be reliably interpreted as proof of clinical efficacy of therapeutic interventions in patients with heart failure.

The significance and treatment of ventricular premature beats (VPBs) in patients without sustained ventricular tachycardia (VT), sudden death, or syncope remains unclear. We undertook a prospective study of programmed electrical stimulation (up to two extrastimuli and burst pacing) in 73 patients (age 60 +/- 10 years) with high-grade VPBs who had no evidence of sustained VT, sudden death, or syncope as determined by 48 hr of monitoring in the cardiac care unit and 48 hr Holter monitoring. Fifty-six patients (76.7%) had atherosclerotic heart disease, 10 (13.7%) had cardiomyopathy or valvular heart disease, and seven (9.6%) had no evident heart disease. Thirty-seven patients (50.7%) had Lown grade IVB VPBs, 30 (41.1%) had Lown grade IVA VPBs, and six (8.2%) had Lown grade III VPBs. Programmed electrical stimulation identified two groups of subjects: group 1 comprised 20 patients (27%) in whom VT or ventricular fibrillation was induced, group 2 comprised 53 patients (73%) in whom no ventricular arrhythmia or only two to four repetitive ventricular responses were induced. There was a significant difference between the presence of atherosclerotic heart disease, old myocardial infarction, and ejection fraction of less than 40% in group 1 compared with group 2. However, there was no significant difference in the grade of VPBs between the two groups. Seventeen of 20 patients from group 1 were placed on antiarrhythmic therapy (defined by programmed electrical stimulation), whereas group 2 patients were randomly assigned to prophylactic antiarrhythmic therapy. A total of 70 patients were followed up for 30 +/- 15 months. The incidence of sustained VT and/or sudden death (31.5% vs 2%; p less than .001) was significantly higher in group 1 compared with group 2.(ABSTRACT TRUNCATED AT 250 WORDS)

Three hundred and one patients who had been hospitalized for acute myocardial infarction, were less than 70 years old, were in sinus rhythm, and did not have complete bundle branch block were stratified before discharge according to age, size of infarction, and type of ventricular arrhythmias as determined on a 6 hr electrocardiogram (ECG). They were thereafter randomly assigned to double-blind treatment with 100 mg bid metoprolol or placebo. Repeat 6 hr ECGs were recorded 3 days and 1, 6, and 12 months after treatment had begun. In the placebo group there was a significant increase in the proportion of patients with complex premature ventricular complexes (PVCs) (i.e., multiform, paired and R-on-T PVCs, or ventricular tachycardia) as well as increased numbers of PVCs in the patients during the follow-up. In contrast, an initial decrease in the number of PVCs (p less than .001) was found in the metoprolol group, whereas the complexity of PVCs was constant in those patients who continued on metoprolol therapy throughout the follow-up period. We conclude that the increase in complexity and number of PVCs that is part of the natural clinical course after myocardial infarction is counteracted by long-term treatment with metoprolol.

To elucidate the mechanisms of reduction of left ventricular end-diastolic pressure by nifedipine in certain individuals, we evaluated cardiac and peripheral hemodynamic responses in 32 patients after they were randomly assigned to nifedipine (20 mg sublingually) or to placebo treatment. Forearm plethysmography was performed during cardiac catheterization with micromanometers. No hemodynamic parameters were changed after placebo. Left ventricular end-diastolic pressure declined by 14% (p less than .02) after nifedipine in patients with impaired left ventricular function, but was unchanged in those with normal function; indexes of peripheral venous hemodynamics (forearm venous tone, forearm volume change) were not affected. In those patients with abnormal left ventricular function, forearm vascular resistance decreased 36% and forearm blood flow increased 31% (p less than .0005 for both), while neither changed in those with normal function. Cardiac output increased by 10% in patients with impaired left ventricular function but was unchanged in the remainder, while calculated total systemic resistance fell by 24% in those with abnormal left ventricular function (p less than .002 for both). Thus, reduction of left ventricular preload by nifedipine is not attributable to venous pooling, but rather this beneficial effect appears to be attributable to improved left ventricular systolic function in response to afterload reduction, particularly in patients with impaired left ventricular function.

This study was designed to test the hypothesis of a possible role of serotonin in the pathogenesis of myocardial ischemia in patients with pure vasospastic angina, since serotonin is known to cause contraction in isolated coronary arteries. This effect, as well as serotonin-induced platelet aggregation, is reversed by ketanserin, a specific S2-receptor blocker. Five male patients (49 to 68 years old) with more than six episodes/day of myocardial ischemia at rest as characterized by ST segment elevation on the electrocardiogram (ECG) were selected for the study after a 2 day run-in period of continuous ECG Holter monitoring in the absence of any therapy except that with sublingual nitrates. In a double-blind crossover protocol they received consecutive infusions of 6 hr each of ketanserin (2 mg/hr iv, preceded by a 10 mg bolus in three patients) and placebo in the following sequence: ketanserin-placebo-ketanserin-placebo in the first and placebo-ketanserin-placebo-ketanserin in the second 24 hr period. The efficacy of the infused drug was tested by exposing platelet-rich plasma, obtained from the study patients at a fixed morning time before and during ketanserin infusions, to a series of serotonin concentrations from 10(-5) to 10(-8)M in a conventional aggregometer. A complete suppression of aggregation curves in the range of serotonin concentrations tested resulted during administration of ketanserin. The efficacy of the drug in preventing ischemic episodes was assessed by computing the ischemic episodes (recorded by Holter monitoring) and nitroglycerin consumption in each 6 hr ketanserin period and in the corresponding placebo period. A total of 171 ischemic episodes were recorded, 33 of which (19%) were symptomatic.(ABSTRACT TRUNCATED AT 250 WORDS)

To determine whether adding blood to a cardioplegic solution affects myocardial preservation, a randomized prospective study was carried out in 60 patients undergoing coronary revascularization to compare the effects of crystalloid potassium cardioplegics (group C) and potassium cardioplegic solutions to which blood has been added (group B) on markers of myocardial metabolism (lactate, inorganic phosphate, base deficit release, glucose and lactate uptake, oxygen extraction), myocardial damage (creatine kinase [CK]-MB levels), and cardiac performance (cardiac index and left atrial pressure). The solution with added blood had a significantly (p less than .05) greater oxygen content, a lower pH, and higher concentrations of potassium, calcium, sodium, and glucose. In group B patients there was a suggestion (p less than .06) of greater uptake of oxygen during the beginning of the initial cardioplegic infusion. During reperfusion there was no evidence of differential release of the metabolites of anaerobiosis and myocardial oxygen extraction and glucose and lactate uptake were similarly depressed in both groups. Likewise, CK-MB release after bypass was the same in both groups. Prompt, adequate functional recovery of cardiac index and left atrial pressure was observed in both groups. It was concluded that although there may be more oxygen available from the blood-containing solution during early infusion, there is no evidence that under the conditions of this investigation adding blood to cardioplegic solution improves myocardial preservation.

Eleven patients with severe left ventricular impairment (mean ejection fraction 24%) and moderate impairment of exercise tolerance underwent a double-blind, placebo-controlled, cross-over trial of the orally administered beta-agonist prenalterol. Exercise hemodynamics and tolerance were measured during bicycle and treadmill exercise after 2 weeks of therapy with placebo or prenalterol. Cardiac index, ejection fraction, and stroke work index were not improved and exercise duration and peak oxygen consumption were not significantly different during the two treatments. During prenalterol treatment heart rate during exercise was consistently reduced. These results show that prolonged therapy with prenalterol does not improve hemodynamics or exercise tolerance and is associated with a diminished heart rate response to exercise.

Defibrillation/cardioversion thresholds were measured in 33 patients undergoing defibrillator implants. Each patient had a 12 cm2 patch placed near the left ventricular apex via a thoracotomy and a 10 cm2 spring lead placed pervenously at the right atrial-superior vena caval junction. Ventricular tachycardia of stable morphology, polymorphic ventricular tachycardia, or ventricular fibrillation was induced four times in each patient and 1, 5, 10, and 25 J truncated exponential shocks with 60% tilt were given in a random sequence. The conversion rate was constant (77%, 86%, 87%, 85%) with increasing energy for ventricular tachycardia but progressively increased for polymorphic ventricular tachycardia and ventricular fibrillation (8%, 33%, 58%, 92%). The ventricular tachycardia acceleration rates for 1, 5, 10, and 25 J were 23%, 14%, 10%, and 15%. Patients not reliably converted with 25 J may require repositioning of leads or two patches. We conclude that for the spring-patch electrodes, increasing energy from 1 to 25 J improves the conversion rate for polymorphic ventricular tachycardia and ventricular fibrillation; the ventricular tachycardia conversion rate is constant. Acceleration of ventricular tachycardia occurs at all energies. Defibrillator implantation requires extensive intraoperative electrophysiologic testing to ensure safe and reliable termination of ventricular tachycardia and fibrillation.

The efficacy of intracoronary urokinase and streptokinase were compared in 80 patients with acute myocardial infarction in a prospective, randomized, double-blind study. Urokinase was infused into the occluded coronary artery at 6000 U/min, and streptokinase was infused at 2000 U/min. Maximal duration of infusion was 2 hr. The frequency of successfully opening the artery was similar for patients receiving urokinase (27 of 45, 60%) and those receiving streptokinase (20 of 35, 57%). Fibrinogen levels after infusion were measured in 63 patients. Nineteen of 29 streptokinase recipients had fibrinogen levels less than 100 mg/dl compared with levels of two of 34 urokinase recipients (p less than .001). Five of 45 (11%) patients receiving urokinase and 10 of 35 receiving streptokinase (29%) had bleeding complications (p less than .05). Major bleeding after early coronary artery bypass surgery was more frequent in the streptokinase group (four of five compared with a similar group of patients receiving urokinase (none of five). This study demonstrates that while urokinase and streptokinase have equal intracoronary thrombolytic efficacy, patients receiving urokinase have less systemic fibrinolysis and less perioperative bleeding with early surgery than do patients receiving streptokinase.

In "post hoc" subgroup analyses, a simple classification system for patients, based on the presence or absence of findings indicative of electrical and/or mechanical complications early during short-term hospitalization, was applied to the data from the Beta-Blocker Heart Attack Trial (BHAT). In the largest subgroup of BHAT patients who had no reported complications, the 25 month mortality was low and the observed benefit of propranolol therapy small. Patients with electrical complications only had intermediate mortality and a pronounced effect of treatment was observed. Those with mechanical complications had the highest mortality and experienced an intermediate relative benefit of beta-blocker treatment. They also reported the most adverse effects. Post hoc analyses should always be interpreted cautiously. It is important to determine whether these findings are present in other completed beta-blocker trials. On the basis of these analyses alone it is suggested that the present practice of prescribing beta-blockers in postinfarction patients should not be altered.

A prospective randomized trial was conducted to evaluate the effects of exercise-based cardiac rehabilitation after myocardial revascularization surgery (MRS) on work capacity (measured in mets) and left ventricular function as determined from ejection fraction (LVEF). Twenty-eight patients undergoing MRS were randomly assigned to experimental (aerobic exercise, n = 19) or control (muscle relaxation and low-level exercise, n = 9) groups. Patients were studied before surgery (T1) and 2 (T2), 8 (T3), and 24 (T4) weeks after surgery with first-pass radionuclide angiography both while they were at rest and during maximal upright cycle ergometric exercise. Subsets of patients were also studied at T2, T3, and T4 at a standard workload of 75 W, and during maximal exercise 1 year after surgery (T5). Work capacity improved in both groups although significantly more so in the experimental group (3.9, 3.8, 6.0, and 7.3 mets and 3.7, 3.7, 4.9, and 5.7 mets at T1, T2, T3, and T4 in the experimental and control groups, respectively). The differences between groups were significant by T3. Peak exercise LVEF increased significantly in both groups from T1 to T2 then decreased at T3 and remained unchanged through T5. Peak exercise LVEF at T3 to T5 remained significantly above that observed at T1. LVEF responses were not related to the exercise program. During a standard workload, heart rate decreased, blood pressure increased, and LVEF did not change in either group. After conclusion of the formal protocol (T4), work capacity and LVEF did not change for either group throughout an additional 6 months (T5).(ABSTRACT TRUNCATED AT 250 WORDS)

Preliminary clinical and laboratory observations suggest that nifedipine might prevent progression of threatened myocardial infarction by reversing coronary spasm or might limit necrosis during the course of acute myocardial infarction. We screened 3143 patients with ischemic pain of greater than 45 min duration and randomly assigned 105 eligible patients with threatened myocardial infarction and 66 with acute myocardial infarction to receive nifedipine (20 mg orally every 4 hr for 14 days) or placebo plus standard care. Treatment was started 4.6 +/- 0.1 hr after the onset of pain. Infarct size index was calculated by the MB-creatine kinase (CK) method and expressed as CK-geq/m2 +/- SE. The incidence of progression to infarction among patients with threatened myocardial infarction was not significantly altered by nifedipine (36 of 48 [75%] for placebo-treated and 43 of 57 [75%] for nifedipine-treated patients). Furthermore, infarct size index was similar among placebo- and nifedipine-treated patients (16.9 +/- 1.5 MB-CK-geq/m2, n = 65, and 17.0 +/- 1.5 MB-CK-geq/m2, n = 68, respectively) with threatened myocardial infarction who exhibited infarction and for those with acute myocardial infarction. Among the 171 eligible patients randomly assigned to drug or placebo, 6 month mortality did not differ significantly (8.5% for placebo vs 10.1% for nifedipine, NS), but mortality in the 2 weeks after randomization was significantly higher for nifedipine-treated patients (0% for placebo compared with 7.9% for nifedipine, p = .018).(ABSTRACT TRUNCATED AT 250 WORDS)

To characterize the potential of nifedipine in the therapy of unstable angina pectoris we implemented a blinded, randomly assigned, titrated schedule of conventional therapy (propranolol, if not contraindicated, and isosorbide dinitrate) or nifedipine for 14 days in 126 patients hospitalized in a coronary care unit for ischemic chest pain of less than 45 min duration. There were no significant differences between conventionally and nifedipine-treated patients with regard to (1) the time to relief of pain as judged by life table analysis, (2) the decrease in anginal attacks per 24 hr from day 0 to day 2 (-2.5 +/- 0.4 for conventional therapy vs; -2.8 +/- 0.3 for nifedipine), (3) the decrease in the number of nitroglycerin tablets consumed per 24 hr (-2.0 +/- 0.5 for conventional vs -2.1 +/- 0.4 for nifedipine therapy), (4) the percentage of patients requiring morphine on day 1 (13% for conventional vs 21% for nifedipine therapy), or (5) the percentage of patients who developed infarction (14% in both groups). Among the 27 patients who did not respond to initial conventional (n = 13) or nifedipine therapy (n = 14), five in each group became pain free when the opposite therapy (either nifedipine or conventional therapy) was added. In the subgroup of 67 patients who were receiving propranolol before randomization, addition of nifedipine was more effective in controlling pain than was an increase in conventional therapy (p = .026). In the subgroup of 59 patients not receiving prior propranolol, initiation of conventional therapy produced more rapid pain relief than initiation of nifedipine therapy alone (p less than .001), which tended to increase heart rate. Thus, for the study population as a whole therapy with nifedipine alone was equivalent to conventional therapy for unstable angina, although this overall equivalence may result from a combination of superiority of nifedipine therapy in patients previously receiving beta-blocker therapy and superiority of beta-blocker therapy in patients not previously receiving beta-blockers.