The dose requirements and duration of effect of transdermal nitroglycerin in patients with heart failure are not clearly established. In a first series of eight patients with chronic heart failure we gave transdermal nitroglycerin in incremental doses until pulmonary capillary wedge pressure fell at least 30% within 4 hr in three consecutive patients. Thus we found that a single dose of 60 mg/24 hr (120 cm2) was the minimal effective dose. Transdermal nitroglycerin or placebo was then given as a single application of 60 mg/24 hr in random double-blind fashion to 15 additional patients with heart failure (eight received transdermal nitroglycerin and seven received placebo), and hemodynamics were monitored for up to 24 hr. After administration of transdermal nitroglycerin, the control pulmonary capillary wedge pressure of 22 +/- 7 mm Hg fell by 6 +/- 6 mm Hg at 2 hr (p less than .05) and reached maximal reduction of 8 +/- 6 mm Hg (p less than .01) at 4 hr. The reduction in wedge pressure remained significant through 12 hr but was no longer statistically significant by 18 hr after administration of the drug. Transdermal nitroglycerin also significantly reduced pulmonary arterial and right atrial pressures as well as pulmonary vascular resistance from 4 through 12 hr but did not affect systemic hemodynamics. No significant hemodynamic changes occurred after administration of placebo. Thus transdermal nitroglycerin is an effective vasodilator in patients with heart failure, but a dose of at least 60 mg/24 hr is needed. Even with this dose, hemodynamic effects do not last beyond 18 hr, suggesting altered absorption or development of tolerance.

A number of uncontrolled studies have indicated that oral administration of amrinone, a phosphodiesterase inhibitor with potent positive inotropic effects in experimental preparations, may be beneficial in patients with chronic congestive heart failure. The present multicenter trial was designed to prospectively evaluate clinical response and change in exercise tolerance during 12 weeks of amrinone therapy in a double-blind, placebo-controlled protocol. Ninety-nine patients with NYHA functional class 3 or 4 congestive heart failure on digitalis and diuretics, of whom 31 were also receiving captopril, were enrolled. After baseline clinical assessment and determination of exercise tolerance, radionuclide left ventricular ejection fraction, and roentgenographic cardiothoracic ratio, patients were randomly assigned to receive amrinone or placebo, beginning at 1.5 mg/kg tid and increasing to a maximum dosage of 200 mg tid. After 12 weeks of therapy or at the last blinded evaluation in patients who did not complete this protocol, there were no significant differences from baseline values between treatment with amrinone or placebo with regard to symptoms, NYHA functional class, left ventricular ejection fraction, cardiothoracic ratio, frequency and severity of ventricular ectopy, or mortality. Exercise tolerance improved significantly from baseline by 37 +/- 10% (mean 163 sec) in patients on amrinone and 35 +/- 11% (mean 149 sec) in patients on placebo, but there was no significant difference between treatments. Adverse reactions were significantly more frequent and more severe on amrinone, occurring in 83% of patients and necessitating withdrawal in 34%.(ABSTRACT TRUNCATED AT 250 WORDS)

In a placebo-controlled, randomized, cross-over, double-blind study of 12 patients with stable exertional angina, we measured at rest and during bicycle exercise the effects of 20 mg of nifedipine administered sublingually on hemodynamics and systemic and regional oxygen extraction and metabolism. Nifedipine decreased systemic vascular resistance by 38% at rest (p less than .001) and by 28% during exercise (p less than .001). Cardiac output increased from 4.6 +/- 0.6 to 6.0 +/- 0.9 liters/min (p less than .001) at rest after nifedipine and from 10.6 +/- 3.7 to 11.8 +/- 3.4 liters/min (p less than .005) during exercise. After nifedipine, the arterial-mixed venous O2 content difference decreased from 4.7 +/- 0.6 to 3.5 +/- 0.5 ml/100 ml (p less than .001) at rest and from 10.5 +/- 1.7 to 8.8 +/- 1.6 ml/100 ml (p less than .001) during exercise. After nifedipine the arterial-iliac venous O2 content difference also decreased at rest, from 5.9 +/- 1.5 to 4.8 +/- 1.7 ml/100 ml (p = .06) but increased during exercise from 13.1 +/- 1.5 to 14.0 +/- 1.8 ml/100 ml (p less than .05). Oxygen consumption was not significantly altered at rest or during exercise. Nifedipine decreased mixed venous carbon dioxide tension (PCO2) during exercise from 53 +/- 3.5 to 50 +/- 4.0 mm Hg (p less than .05) but increased iliac venous PCO2 slightly from 61 +/- 4.6 to 63 +/- 5.2 mm Hg (p less than .01). Exercise pH was not significantly altered, but arterial lactate increased more after nifedipine (2.65 +/- 1.95 mmol/liter placebo, 3.54 +/- 2.74 mmol/liter nifedipine; p less than .05). Thus nifedipine produces similar changes in O2 extraction in mixed venous and iliac venous blood at rest but directionally opposite changes during exercise. The data support the hypothesis that nifedipine does not alter the distribution of cardiac output to the legs at rest, but during dynamic leg exercise reduces the redistribution of cardiac output to the legs. This probably results from the shunting of blood flow away from exercising muscles by the generalized vasodilatation of nifedipine.

The afterload reduction and myocardial oxygen sparing that results after administration of calcium antagonists suggests a possible role for these drugs in intervention after onset of acute myocardial infarction, but their use in this setting is limited by the possibility that left ventricular failure will develop. Tiapamil is a new verapamil congener. The hemodynamic effects of this drug (1 mg/kg followed by 25 micrograms/kg/min over 36 hr) were studied in 30 patients randomly assigned in a double-blind manner to a tiapamil or control group within 12 hr of the onset of acute myocardial infarction as diagnosed by Swan-Ganz catheterization and gated blood pool scans. Tiapamil reduced heart rate from 83 +/- 20 beats/min (mean +/- SD) before to 74 +/- 19 beats/min after drug (over an average 36 hr), arterial pressure from 128 +/- 22/87 +/- 14 to 118 +/- 16/74 +/- 11 mm Hg, rate-pressure product from 10,695 +/- 3492 to 8800 +/- 2550 units, and systemic vascular resistance from 1732 +/- 351 to 1400 +/- 350 dynes X sec X cm-5. Tiapamil also increased stroke volume index from 34.7 +/- 12.1 to 41.6 +/- 12.0 ml/m2, left ventricular ejection fraction from 50.1 +/- 14.8% to 56.4 +/- 17.4% (at 24 hr), left ventricular end-diastolic volume index from 71.3 +/- 23.1 to 80.5 +/- 23.7 ml/m2, and peak diastolic filling rate (an index of diastolic relaxation) from 2.1 +/- 0.9 to 2.6 +/- 0.8 end-diastolic volumes/sec (p less than .05 for all changes). Cardiac index, wedge pressure, left ventricular end-systolic volume, and PR interval remained unchanged.(ABSTRACT TRUNCATED AT 250 WORDS)

The clinical efficacy and safety of transvenous cardioversion for termination of sustained ventricular tachycardia (VT) were examined by a prospective randomized study design in 22 patients (19 men, three women; mean age 64 +/- 9 years) with organic heart disease and sustained VT. Patients were randomly assigned to undergo an incremental low-energy protocol from 0.03 to 2.2 J (group A, 11 patients) or an incremental high-energy protocol from 0.5 to 10.0 J (group B, 11 patients). Transvenous cardioversion was performed during electrophysiologic studies in the control (drug-free) state and during serial antiarrhythmic drug testing in all patients. Both groups were comparable for demographic, disease and functional status, and electrophysiologic parameters. A total of 77 episodes of VT (group A, 45; group B, 32) were analyzed. The overall efficacy of transvenous cardioversion for termination of VT was 62% (group A 56% vs group B 72%; p less than .01). Antiarrhythmic drug therapy did not significantly enhance efficacy of transvenous cardioversion (control 59% vs drug 65%; p greater than .2). Stepwise discriminant analysis correlated successful transvenous cardioversion with longer VT cycle length (p less than .0005), higher energy (p less than .025), lower energy waveform tilt (p less than .025), shorter time to initial cardioversion attempt (p less than .025), and shorter QRS duration in sinus rhythm (p less than .05). Acceleration of VT was frequent (8% incidence per delivered shock). Thirty-one percent of all incremental shock protocols were terminated because of this complication. After cardioversion, transient arrhythmias were common (bradyarrhythmias 23%, supraventricular tachyarrhythmias 12%). Displacement of electrode catheters after transvenous cardioversion was uncommon (3%).(ABSTRACT TRUNCATED AT 250 WORDS)

Many vasodilators have been tried as antianginal agents, but the reflex increase in sympathetic tone produced by these drugs necessitate their use with caution in patients with angina. In the first part of this study, captopril was given to 14 patients with angina and systolic arterial pressures of greater than 120 mm Hg. Over the short term, captopril decreased arterial blood pressure (from 110 +/- 18 to 98 +/- 18 mm Hg, p less than .01) without increasing heart rate (75 +/- 15 vs 74 +/- 15 beats/min), arterial concentrations of epinephrine (0.38 +/- 0.28 vs 0.34 +/- 0.25 nM) or norepinephrine (2.7 +/- 2.1 vs 2.8 +/- 2.1 nM), or transmyocardial norepinephrine balance (216 +/- 254 vs 146 +/- 170 p mol/min). Captopril decreased average myocardial oxygen consumption (9.7 +/- 4.1 to 8.2 +/- 2.7 ml/min, p less than .01). Given over the long term (mean 5.5 months), captopril decreased the severity of angina from NYHA classification 3.0 +/- 0.8 to 1.6 +/- 0.8. In the second part of this study, captopril was given in a prospective, randomized, double-blind, placebo-controlled study to 21 patients with stable exercise-induced angina and systolic arterial pressures greater than 120 mm Hg. Captopril increased exercise time (309 +/- 137 vs 374 +/- 142 sec, p less than .05) without changing anginal threshold (rate-pressure product 17.0 +/- 6.0 vs 17.1 +/- 5.6 X 10(-3)). We conclude that captopril decreases mean arterial pressure without causing a reflex increase in myocardial sympathetic tone.(ABSTRACT TRUNCATED AT 250 WORDS)

A multivariate logistic regression equation was used to evaluate variables related to successful intracoronary thrombolytic therapy. One hundred seventeen patients with a totally occluded infarct-related artery were randomly given ostial infusions of urokinase or streptokinase in a blinded study. The opening rate was 57%. The agent used and time from onset of symptoms to beginning of treatment did not significantly influence opening rate (p greater than .25). The site of occlusion was a strong predictor of opening rate (p = .0004). The anterior descending coronary artery was successfully opened more frequently than the left circumflex or right coronary artery (p = .012). Presence of collaterals adversely affected the recanalization rate in all groups (p = .0004). These variables had an additive effect on the probability of opening. Patients with proximal anterior descending occlusion and no collaterals had a 90% recanalization rate, while those with distal occlusions in vessels other than the anterior descending and with collaterals had only a 24% chance for reperfusion. Thus location of occlusion and presence or absence of collaterals may strongly influence opening rates.

The efficacy of a single oral dose combination of 120 mg diltiazem and 160 mg propranolol in terminating paroxysmal supraventricular tachycardia (PSVT) was evaluated in 15 patients. All 15 patients underwent electrical induction of PSVT that lasted longer than 15 min, and all underwent randomized crossover placebo and diltiazem and propranolol studies on 2 consecutive days. On each day PSVT was induced and placebo or diltiazem and propranolol was administered 15 min later. Electrical conversion of PSVT was performed when severe symptoms occurred or at the end of 240 min. With placebo PSVT lasted 164 +/- 89 (mean +/- SD) min; four patients had spontaneous conversion. With diltiazem and propranolol PSVT lasted 39 +/- 49 min (p less than .001); 14 patients had spontaneous conversion in an average of 27 +/- 15 min. None of the 14 patients had electrical reinduction of sustained PSVT after conversion. The sinus nodal recovery time during spontaneous or electrical conversion of PSVT was 911 +/- 459 msec with placebo and 1076 +/- 270 msec with diltiazem and propranolol (NS). Two patients developed transient second-degree atrioventricular block and junctional rhythm while on diltiazem and propranolol. Serum diltiazem and propranolol levels (ng/ml) after diltiazem and propranolol in five patients were, respectively, 49 +/- 26 and 108 +/- 101 at 15 min, 232 +/- 147 and 228 +/- 148 at 30 min, 254 +/- 169 and 370 +/- 393 at 45 min, 280 +/- 115 and 209 +/- 189 at 60 min, 188 +/- 72 and 268 +/- 264 at 120 min, and 118 +/- 57 and 265 +/- 148 at 240 min.(ABSTRACT TRUNCATED AT 250 WORDS)

The effects of bepridil, a calcium antagonist with a half-life of approximately 42 hr, were assessed in a double-blind, randomized, placebo-controlled crossover trial. Forty-four patients (39 men, five women) with exercise-induced angina pectoris and ST segment depression with exercise testing (modified Bruce protocol) were studied. Compared with placebo bepridil (400 mg daily) increased total exercise time, time to onset of angina, time to 1 mm of ST segment depression, time to 2 mm of ST segment depression, and total work achieved (all p less than or equal to .001). Both frequency of angina and nitroglycerin consumption decreased during the bepridil compared with the placebo period (p = .02 and .03, respectively). Minor side effects were noted during both the bepridil and placebo phases. Four patients experienced side effects that limited therapy (dizziness in three and abnormal results of liver function tests in one) and one patient died during the bepridil phase. This study suggests that bepridil, 400 mg daily, is effective for the treatment of exercise-induced myocardial ischemia and angina pectoris.

Forty-five patients with acute transmural myocardial infarction and angiographically confirmed complete coronary occlusion were prospectively randomized, two for one, to treatment of acute coronary thrombosis with intravenous recombinant human tissue-type plasminogen activator (rt-PA) or placebo. Each of five additional consecutive patients was treated with a high dose of rt-PA for 2 hr. Twenty-five of 33 patients (75%) receiving 0.5 to 0.75 mg/kg of rt-PA over 30 to 120 min had angiographically proven recanalization within 90 min of initiation of therapy. Only one of 14 patients given placebo had spontaneous recanalization within 45 min (p less than .001). Thirteen placebo-treated patients were crossed over to the intracoronary rt-PA group. Nine (69%) exhibited subsequent recanalization within 45 min. Levels of circulating fibrinogen decreased after treatment with rt-PA by an average of only 8% of baseline values. None of the patients manifested a depletion of fibrinogen level to below 100 mg/dl. Six patients who were completely unresponsive to rt-PA were subsequently treated with intracoronary streptokinase and none responded. Thus, either intravenous or intracoronary rt-PA induced coronary thrombolysis without eliciting clinically significant fibrinogenolysis in patients with evolving myocardial infarction due to thrombotic coronary occlusion.

The oral administration of neomycin or niacin as single-drug therapy can significantly lower total and low-density lipoprotein cholesterol concentrations in patients with type II hyperlipoproteinemia. However, in the majority of patients treated with one of these drugs as sole therapy plasma lipid and lipoprotein concentrations do not normalize. The effect of combined neomycin (2 g/day) and niacin (3 g/day) treatment on the plasma lipoprotein concentrations was determined in 25 type II hyperlipoproteinemic patients in a double-blind, randomized, placebo-controlled, crossover clinical trial. Treatment with neomycin was well tolerated by all 25 study patients and significantly reduced total and low-density lipoprotein cholesterol concentrations by 23% and 29%, respectively (p less than .05). In contrast to the well-tolerated neomycin regimen, 11 patients (44%) were unable to continue niacin treatment because of adverse side effects. In the 14 patients treated with both neomycin and niacin, niacin further lowered the concentrations of total and low-density lipoprotein cholesterol by 18% and 25%, respectively, and increased high-density lipoprotein cholesterol by 32% (p less than .05) compared with that in the patients receiving neomycin plus niacin placebo. Compared with diet-only therapy, combined treatment with neomycin plus niacin reduced the total plasma cholesterol concentration by 36%, low-density lipoprotein cholesterol by 45%, and the low-density lipoprotein/high-density lipoprotein ratio by 46% and it increased plasma high-density lipoprotein concentrations by 24% (p less than .001). During the study, 80% of all the study patients and 92% of the patients who complied with the combined regimen normalized their total and low-density lipoprotein concentrations.(ABSTRACT TRUNCATED AT 250 WORDS)

Enzymatic estimates of myocardial infarct size based on plasma levels of MB creatine kinase (MB-CK) were compared with anatomic infarct size in 49 human hearts obtained at autopsy. The patients studied had been enrolled in the Multicenter Investigation of Limitation of Infarct Size (MILIS) study program within 18 hr of the onset of acute infarction and were treated at one of five participating hospitals. Infarct size was estimated from serial measurements of plasma MB-CK made at the core laboratory for CK analysis. Hearts obtained at autopsy were studied independently by the core pathology laboratory without knowledge of the MB-CK levels or clinical results. Data from the two laboratories were compared at the data coordinating center. Of 49 hearts, 12 were excluded either because anatomic infarct size could not be established or because the infarct occurring at the time of enrollment in the MILIS study could not be distinguished with certainty from other infarcts. Of the remaining 37 hearts, peak MB-CK level was available in 36, but samples sufficient for estimation of infarct size were available in only 25. The overall correlation coefficient (Spearman) was .87 for these 25 hearts, indicating that enzymatic estimates of infarct size correlate closely with anatomic measurements. The results indicate that CK estimates of myocardial infarct size represent a valid clinical end point for assessing myocardial infarct size, and the effect of therapy thereon, in groups of treated and control patients.

The Western Washington Intracoronary Streptokinase In Myocardial Infarction Trial enrolled 250 patients with acute myocardial infarction. After the coronary angiographic diagnosis of thrombosis, patients were randomly assigned to receive either conventional therapy with heparin or intracoronary streptokinase followed by heparin. Of the 232 patients who survived at least 60 days, 207 (89%) underwent radionuclide ventriculographic determination of global and regional ejection fraction at a single institution at 62 +/- 35 days after infarction. In the first 100 patients, infarct size was also determined by quantitative single-photon emission tomographic imaging with thallium-201 (201Tl) and expressed as a percentage of the left ventricle with a perfusion defect. Overall, global ejection fraction did not differ between patients treated with streptokinase (45.9 +/- 13.9%; n = 115) and control patients (46.1 +/- 14.4%; n = 92, p = NS). Similarly, the regional posterolateral, inferior, and anteroseptal ejection fraction did not differ between the two groups. Infarct size as measured by 201Tl tomography was 19.4 +/- 12.8% (n = 52) of the left ventricle for the streptokinase group and 19.6 +/- 11.8% (n = 48; p = NS) for the control group. When patients were compared within groups by electrocardiographic location of infarction, time to treatment, or the presence or absence of vessel opening, there were no significant differences between streptokinase and control patients. Statistical inclusion of the 18 patients who died early and were unavailable for study also failed to modify the results, except for a possible reduction in inferior infarct size as measured by 201Tl tomography.(ABSTRACT TRUNCATED AT 250 WORDS)

To evaluate the efficacy of exercise training for increasing functional capacity in the 6 months after clinically uncomplicated myocardial infarction, 198 men 52 +/- 9 years of age participated in a training study. They were randomly assigned to one of four exercise protocols: 8 to 26 weeks of training at home (group 1, n = 66) or in a group program (group 2, n = 61) following treadmill testing performed 3 weeks after infarction, treadmill testing at 3 weeks without subsequent training (group 3, n = 34), and treadmill testing for the first time at 26 weeks (control, n = 37). At 26 weeks functional capacity was significantly higher in patients training at home or in a group program than that in patients without training or in control patients: 8.1 +/- 1.5, 8.5 +/- 1.3, 7.5 +/- 1.8, and 7.0 +/- 1.7 METs, respectively (p less than .05 and p less than .001). No significant differences in functional capacity were noted between patients training at home and those in a group program. No training-related complications occurred. Home and group training are equally effective in increasing functional capacity of low-risk patients after myocardial infarction.

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)