Low-dose enoximone improves exercise capacity in chronic heart failure. Enoximone Study Group.

OBJECTIVES: This study was designed to evaluate the effects of low-dose enoximone on exercise capacity. BACKGROUND: At higher doses the phosphodiesterase inhibitor, enoximone, has been shown to increase exercise capacity and decrease symptoms in heart failure patients but also to increase mortality. The effects of lower doses of enoximone on exercise capacity and adverse events have not been evaluated. METHODS: This is a prospective, double-blind, placebo-controlled, multicenter trial (nine U.S. centers) conducted in 105 patients with New York Heart Association class II to III, ischemic or nonischemic chronic heart failure (CHF). Patients were randomized to placebo or enoximone at 25 or 50 mg orally three times a day. Treadmill maximal exercise testing was done at baseline and after 4, 8 and 12 weeks of treatment, using a modified Naughton protocol. Patients were also evaluated for changes in quality of life and for increased arrhythmias by Holter monitoring. RESULTS: By the protocol-specified method of statistical analysis (the last observation carried-forward method), enoximone at 50 mg three times a day improved exercise capacity by 117 s at 12 weeks (p = 0.003). Enoximone at 25 mg three times a day also improved exercise capacity at 12 weeks by 115 s (p = 0.013). No increases in ventricular arrhythmias were noted. There were four deaths in the placebo group and 2 and 0 deaths in the enoximone 25 mg three times a day and enoximone 50 mg three times a day groups, respectively. Effects on degree of dyspnea and patient and physician assessments of clinical status favored the enoximone groups. CONCLUSIONS: Twelve weeks of treatment with low-dose enoximone improves exercise capacity in patients with CHF, without increasing adverse events.

Usefulness of technetium-99m sestamibi infarct size in predicting posthospital mortality following acute myocardial infarction.

In this multicenter study, 249 patients who underwent tomographic technetium-99m sestamibi infarct size measurement at hospital discharge were followed up for a median duration of 7 months. Infarct size was significantly associated with mortality (chi-square = 5.8, p = 0.02) and could stratify patients into lower and higher risk subsets: 1-year mortality 2% for infarct size < 14% versus 8% for infarct size > or = 14% of the left ventricle.

Intercenter variability in outcome for patients treated with direct coronary angioplasty during acute myocardial infarction.

BACKGROUND: Direct coronary angioplasty is an effective therapy for acute myocardial infarction, but its success may be dependent on both ready availability and operator skill. The purpose of this study was to investigate the impact of the center performing direct coronary angioplasty for acute myocardial infarction while controlling for parameters known to affect outcome. METHODS AND RESULTS: The study group consisted of 99 patients with ST elevation who were treated with direct angioplasty in four high-volume centers. Patients were injected with technetium-99m sestamibi intravenously and then taken to the cardiac catheterization laboratory. Antegrade flow was graded before and after direct coronary angioplasty. Single photon emission computed tomography was performed 1 to 6 hours after injection to measure myocardium at risk and residual blood flow to the jeopardized zone using previously published quantitative methods. A repeat sestamibi injection and tomographic acquisition were performed at hospital discharge to measure actual infarct size. There were no significant differences by center for baseline clinical characteristics, mean myocardium at risk (29% to 37% left ventricle [LV]), time to reperfusion (3.1 to 4.1 hours), residual blood flow, infarct location, or antegrade flow. Despite these similarities, there were differences in outcome measures by center. Mean infarct size was as follows: center 1, 15%; center 2, 12%; center 3, 10%, center 4, 23% (all LV; p = 0.11 ). Mean left ventricular ejection fraction at discharge also demonstrated significant differences: center 1, 0.57; center 2, 0.47; center 3, 0.53; center 4, 0.47 (p = 0.002). The prevalence of Thrombolysis in Myocardial Infarction grade 3 flow after angioplasty significantly differed by center: center 1, 92%; center 2, 94%; center 3, 87%; center 4, 71 %; (p = 0.01). There was a low mortality rate for all four centers ranging from 0% to 6%. After adjustment for myocardium at risk, residual blood flow, and time to reperfusion, the primary outcome of the center where the angioplasty was performed was an independent determinant of both infarct size and left ventricular ejection fraction. CONCLUSION: The success of direct coronary angioplasty in reducing infarct size and preserving left ventricular function depends on the center performing the procedure. Direct measurement of the effectiveness of this reperfusion modality in community practice is required to assess the impact of this effect.

Efficacy of Nicardipine for Long-Term Therapy of Chronic Stable Angina.

BACKGROUND: Although angina is a chronic disease, most clinical trials evaluating antianginal therapy are of a few weeks or months in duration. METHODS AND RESULTS: To evaluate the effects of nicardipine, a second-generation dihydro-pyridine calcium channel blocker, as long-term therapy, patients with chronic stable angina were treated for 1 year with open-label nicardipine. Anginal symptoms were controlled with 20 mg tid in 24%, 30 mg tid in 34%, and 40 mg tid in 42%. Of 72 patients completing the 1-year trial, only 14 (19%) had required the addition of long-acting nitrates for control of symptoms. The remaining 57 patients, who had anginal symptoms controlled with nicardipine alone, were continued into the 3-week, double-blind period and were randomized to continue their usual dose of nicardipine or placebo. Throughout the 1-year, open-label treatment period, the number of anginal episodes and exercise parameters of angina were significantly reduced with nicardipine. CONCLUSIONS: During the double-blind period, the patients who continued on nicardipine had significantly greater exercise time and time to onset of angina than patients who were randomized to placebo. The exercise parameters in the patients randomized to placebo were improved over baseline after 1 year of therapy; however, the improvement with nicardipine was significantly greater.

Comparison of primary coronary angioplasty and intravenous thrombolytic therapy for acute myocardial infarction: a quantitative review.

OBJECTIVE: To provide a quantitative review of the treatment effects of primary coronary angioplasty vs intravenous thrombolysis for acute myocardial infarction. DATA SOURCES: Ten randomized trials were identified through computerized bibliographic search of MEDLINE from January 1985 through March 1996 and by queries of principal investigators. STUDY SELECTION: Single-center and multicenter randomized trials comparing primary angioplasty with intravenous thrombolytic therapy among 2606 patients were included. Four trials compared angioplasty with streptokinase, 3 compared angioplasty with a 3- to 4-hour infusion of tissue-type plasminogen activator, and 3 compared angioplasty with "accelerated" administration of tissue-type plasminogen activator over 90 minutes. DATA EXTRACTION: Each investigator provided definitions and exact data for outcome events. Odds ratios (ORs), 95% confidence intervals (CIs), and P values were calculated using exact tests for categorical data. DATA SYNTHESIS: Mortality at 30 days or less was 4.4% for the 1290 patients treated with primary angioplasty compared with 6.5% for the 1316 patients treated with thrombolysis (34% reduction; OR, 0.66; 95% CI, 0.46-0.94; P=.02). The effect was similar among thrombolytic regimens, and no subgroup demonstrated a significant reduction in death. The rates of death or nonfatal reinfarction were 7.2% for angioplasty and 11.9% for thrombolytic therapy (OR, 0.58; 95% CI, 0.44-0.76; P<.001). Angioplasty was associated with a significant reduction in total stroke (0.7% vs 2.0%; P=.007) and hemorrhagic stroke (0.1% vs 1.1%; P<.001). CONCLUSIONS: Based on outcomes at hospital discharge or 30 days, primary angioplasty appears to be superior to thrombolytic therapy for treatment of patients with acute myocardial infarction, with the proviso that success rates for angioplasty are as good as those achieved in these trials. Data evaluating longer-term outcomes, operator experience, and time delay before treatment are needed before primary angioplasty can be universally recommended as the preferred treatment.

Poloxamer-188 as an adjunct to primary percutaneous transluminal coronary angioplasty for acute myocardial infarction.

Poloxamer-188 is a surfactant polymer with antithrombotic and hemorheologic properties that make it potentially useful as an adjunct to acute reperfusion strategies. Animal studies and early human studies have documented poloxamer-188 to be effective at improving myocardial salvage when used as an adjunct to intravenous thrombolytic therapy for acute myocardial infarction. The current trial was a prospective pilot study involving 150 patients who were randomized in a 2:1 fashion to a poloxamer-188 infusion for 48-hours versus placebo. The poloxamer-188 infusion was well tolerated subjectively. The only clinically significant laboratory abnormality noted was an elevation in the serum creatinine above 2.0 g/dl in 12% (n = 12) of the 98 poloxamer-188 treated patients versus 1 of the 52 (2%) of the placebo treated patients (p = 0.048). Clinical end points including reinfarction (1% vs 4%), cardiogenic shock (7% vs 6%), and death (9% vs 4%) were statistically similar in the poloxamer-188 and placebo groups, respectively (p = NS). Using quantitative nuclear techniques, final infarct size and myocardial salvage were statistically similar in the poloxamer-188 and placebo groups. Mean left ventricular ejection fractions 1 week post after infarction were 51% +/- 12% in the poloxamer-188 group and 52% +/- 13% in the placebo group (p = NS). Final infarct size, was not altered by the poloxamer- 188 infusion; however, it was significantly correlated with normal perfusion (Thrombolysis in Myocardial Infarction grade 3 flow) in the infarct vessel after angioplasty. This study documented poloxamer-188 to be ineffective as an adjunct to primary angioplasty for acute myocardial infarction and resulted in azotemia in 12% of the patients.

Comparative efficacy of short-term intravenous infusions of milrinone and dobutamine in acute congestive heart failure following acute myocardial infarction. Milrinone-Dobutamine Study Group.

The purpose of this study was to compare the hemodynamic and clinical effects of milrinone, a vasodilating and positive inotropic agent, with those of dobutamine in patients with congestive heart failure (CHF) following acute myocardial infarction (AMI). Thirty-three patients in Killip classification II or III within 12 h to 5 days after AMI were randomized in a multicenter, open-label clinical trial to receive a 24-h infusion of milrinone or dobutamine. Drugs were titrated to achieve at least a 30% increase in cardiac index (CI) from mean baseline or at least a 25% decrease in mean pulmonary capillary wedge pressure (MPCWP) from baseline. Both drugs improved CI, MPCWP, and other hemodynamic parameters. Criteria for decrease in MPCWP were met by 94% (15/16) of the milrinone-treated patients and 57% (8/14) of dobutamine-treated patients (p = 0.03). Both groups met the minimum efficacy criterion for CI. Maximal reduction in MPCWP over 0-3 h was greater in the milrinone group (-53.2%) than in the dobutamine group (-31.0%; p < or = 0.01); reductions were sustained over 24 h. Both drugs improved echocardiographic global ejection fraction and were generally well tolerated. The short-term infusion of milrinone may have a role in the management of CHF following AMI, especially when the aim is the rapid reduction of pulmonary congestion.

Surgical intervention in acute myocardial infarction: an historical perspective.

Acute myocardial infarction is an evolving event that lends itself well to surgical intervention. An historical review of surgery of acute myocardial infarction, with specific emphasis on the Spokane data, shows that this can be done safely and efficiently with myocardial salvage. Those people who were operated on within 6 hours of the onset of symptoms of acute myocardial infarction had a clear reduction in hospital mortality incidence and a better long-term result. The conclusion of our review is that emergency coronary artery bypass grafting for acute evolving myocardial infarction should be considered as a therapeutic option in every patient. All other modalities of therapy should be compared with the results of acute bypass surgery.

Factors influencing myocardial salvage with primary angioplasty.

BACKGROUND: The purpose of this study was to evaluate the factors influencing the salvage of jeopardized myocardium in patients treated with primary angioplasty for acute myocardial infarction. METHODS AND RESULTS: This multicenter study involved 59 patients with acute myocardial infarction who underwent primary angioplasty without antecedent thrombolytic therapy and paired baseline (before angioplasty) and predischarge tomographic perfusion imaging by quantitative 99mTc-labeled sestamibi techniques for assessing the initial area at risk and eventual infarct size. Of the 59 patients who underwent primary angioplasty, Thrombolysis In Myocardial Infarction (TIMI) level 3 perfusion was restored in the infarct vessel in 54 patients (92%). On average, approximately one third of the left ventricular myocardial mass was initially jeopardized by the infarction in progress; eventual infarct size was 18% +/- 15% of the left ventricle; myocardial salvage was 16% +/- 17% of the left ventricle. Primary angioplasty salvaged 46% +/- 50% of initially jeopardized myocardium. Factors correlated with myocardial salvage included elapsed time from onset of pain to reperfusion, infarct location (anterior infarcts had more myocardial salvage than inferior infarcts), and residual flow to the infarct zone at preangioplasty baseline levels. In the five patients reperfused less than 2 hours from onset of pain, 80% of the jeopardized myocardium was salvaged. Myocardial salvage beyond 2 hours was much more variable. CONCLUSIONS: Primary angioplasty was highly effective at restoring normal perfusion in the infarct vessel and salvaging jeopardized myocardium. The myocardial salvage was highly variable and correlated with elapsed time to reperfusion, baseline residual flow to the infarct zone, and infarct location.

Dose-ranging study with a new two-chain rt-PA in patients with acute myocardial infarction: a multicenter trial.

Tissue-type plasminogen activator (t-PA) derived from a melanoma cell line was first used in patients with acute myocardial infarction in the early 1980s. Recombinant DNA technology then allowed production of large amounts of t-PA. The TIMI-I trial used a two-chain recombinant (rt-PA) product. A predominantly single-chain rt-PA (alteplase) was used in the majority of the TIMI II trial. The present study used a different form of two-chain rt-PA (duteplase) to determine the effective dose for thrombolysis at 60 min, and to evaluate time to reperfusion, reocclusion at 72-96 h, coagulation profiles, and bleeding events. Duteplase was given intravenously to 75 patients a mean of 3.8 +/- 1 h after the onset of myocardial infarction. Following angiography demonstrating coronary occlusion, 23 patients received a low dose of duteplase [0.16-0.29 million international units per kilogram (MIU/kg)] over 60 min followed by a 5-h infusion in conjunction with heparin, 25 patients received a middle dose (0.30-0.41 MIU/kg) and 23 patients received a high dose (0.43-0.74 MIU/kg). Angiography was then performed every 15 min x 4. Progressive recanalization occurred over 60 min (median 45 min) with an overall success rate of 59% (mean 60-min dose: 0.37 MIU/kg). No dose-response relationship was observed. The reocclusion rate was 9% at 72-96 h. Reductions in fibrinogen and plasminogen correlated with dose, but clinical events did not.(ABSTRACT TRUNCATED AT 250 WORDS)

Myocardial infarct artery patency and reocclusion rates after treatment with duteplase at the dose used in the International Study of Infarct Survival-3. Burroughs Wellcome Study Group.

Duteplase, 98% double-chain recombinant tissue-type plasminogen activator, was administered intravenously in 488 patients with acute myocardial infarction in a multicenter, open, safety and patency study. Duteplase dosing was based on body weight. Duteplase was administered as a bolus of 0.04 MIU/kg of thrombolytic activity followed by 0.36 MIU/kg over 1 hour and 0.067 MIU/kg/hour for 3 additional hours. The patency rate of the infarct-related artery at 90 minutes was 69% (330 of 478). The reocclusion rate at 3 to 48 hours was 6% (18 of 301). Reinfarction occurred in 7.6% of patients (37 of 488), but 12 reinfarctions occurred after coronary angioplasty. Serious bleeding occurred in 7.6% of patients (37 of 488), predominantly at the catheterization entry site. There were 3 instances of central nervous system bleeding, 1 fatal. Fibrinogen levels declined to 83% of baseline at 24 hours. Weight-based dosing may explain the low incidence of serious bleeding in this study. The in-hospital mortality was 6.6% (32 of 488). This study documents that the dose of duteplase used in the International Study of Infarct Survival-3 results in a 90-minute coronary artery patency rate and safety profile comparable to those reported in published studies on the approved dose of alteplase.

Comparison of propranolol, diltiazem, and nifedipine in the treatment of ambulatory ischemia in patients with stable angina. Differential effects on ambulatory ischemia, exercise performance, and anginal symptoms. The ASIS Study Group.

Episodes of transient myocardial ischemia during ambulatory activities are common in patients with stable coronary artery disease and who are often asymptomatic. Selection of therapy for episodes of asymptomatic ischemia is limited by a lack of direct comparative studies. To determine the most effective monotherapy for patients with stable angina and a high frequency of asymptomatic ischemic episodes, propranolol-LA (mean daily dose, 293 mg), diltiazem-SR (mean daily dose, 350 mg), nifedipine (mean daily dose, 79 mg) were each compared with placebo, each for 2 weeks, in a randomized, double-blinded, crossover trial. Entry criteria were a positive exercise treadmill test during placebo therapy characterized by 1.0 mm or more ST segment depression and angina pectoris, and six or more episodes of transient ST segment depression of 1.0 mm or more on a 48-hour ambulatory electrocardiogram. One hundred ninety-four patients were screened, 63 were eligible and received randomized therapy, of which 56 patients completed at least two of the four treatment periods and were included in an intent-to-treat analysis. Fifty patients completed all four treatment phases and were included in the protocol-completed analysis. Anti-ischemia efficacy was assessed by 48-hour ambulatory electrocardiographic monitoring, exercise treadmill tests, and anginal diaries. Ninety-four percent of all episodes of ambulatory ischemia were asymptomatic. Compared with placebo, only propranolol was associated with a marked reduction in all manifestations of asymptomatic ischemia during ambulatory electrocardiographic monitoring (2.3 versus 1.0 episodes/24 hr; mean duration of ischemia per 24 hours, 43.6 versus 5.7 minutes; both p less than 0.0001). Diltiazem's reduction of the frequency of episodes compared with placebo (2.3 versus 1.9 episodes/24 hr) was associated with a trend (p = 0.08) in the protocol-completed analysis and with a significant reduction in the intent-to-treat analysis (p = 0.03). Nifedipine had no significant effect on any measured variable of ambulatory ischemia. The dosages of medication used may have been excessive for some patients, and a more beneficial effect may have been evident at a lower dose. In contrast to the marked effects of the active agents on ambulatory asymptomatic ischemia, the effects on exercise performance and angina pectoris were slight. The active agents modestly improved treadmill exercise duration time until 1 mm ST segment depression (3%), and only propranolol and diltiazem had significant effects. Only diltiazem significantly prolonged the total exercise time. Anginal frequency was significantly decreased by both propranolol and diltiazem.(ABSTRACT TRUNCATED AT 400 WORDS)

Randomized double-blind comparison of side effects of nicardipine and nifedipine in angina pectoris. The Nicardipine Investigators Group.

Nicardipine and nifedipine are structurally similar dihydropyridine calcium channel blockers with demonstrated efficacy in the treatment of stable angina pectoris. The present study was a prospective randomized trial designed to evaluate the relative incidence of dizziness, flushing, headache, pedal edema, and palpitations during use of these drugs in patients with angina pectoris. Of 250 patients who entered into the comparative treatment part of the study, 140 patients were susceptible to developing symptoms to nifedipine as identified during a 1-month open-label treatment with nifedipine. These patients were compared with a parallel cohort of 110 patients, who were identified during the same open-label period, but remained mostly asymptomatic. After a 1-week washout of nifedipine, equal numbers of patients in each cohort began an 8-week period of randomized, double-blind treatment with nifedipine (20 mg three times daily) or nicardipine (30 mg three times daily). Patients who experienced these symptoms during the open-label nifedipine treatment had a higher incidence of the same symptoms during the blinded treatment regimen. Nicardipine-treated patients had a lower incidence of each of the symptoms than did the nifedipine-treated patients. Statistically significant differences were reported for dizziness, the most common of the side effects. Patients who were free of these symptoms in the open-label period usually remained free of them in the blinded comparison. However, even among those free of dizziness during the open-label nifedipine treatment, more patients reported experiencing dizziness in the blinded phase from nifedipine than from nicardipine (18% vs 6%; p = 0.02).

Medical and surgical management of early Q wave myocardial infarction. I. Effects of surgical reperfusion on survival, recurrent myocardial infarction, sudden death and functional class at 10 or more years of follow-up.

To define the outcome of patients given medical or surgical therapy for Q wave myocardial infarction, 387 patients were followed up for 10 to 13 years (mean 11.4). On study entry the groups had similar distributions for variables such as mean age, gender, previous myocardial infarction, abnormal creatine kinase activity, area of infarction, number of vessels diseased and clinical classification. The hospital mortality rate of the medical versus surgical group was 11.5% (23 of 200) versus 5.8% (11 of 187) (p = 0.07). Early reperfusion (that is, less than or equal to 6 h) resulted in a lower mortality rate than did medical therapy--2% (2 of 100) versus 11.5% (23 of 200) (p less than 0.05)--whereas the hospital mortality rate with late reperfusion was 10.3% (9 of 87). The long-term mortality rate of the medical and surgical groups was 41% (82 of 200) versus 27% (51 of 187) (p = 0.0007) with use of an adjusted Cox proportional hazards model. In the survivors, the differences between medical and surgical groups in recurrent myocardial infarction, mortality associated with reinfarction and sudden death were prospectively followed and evaluated by the life table method. Recurrent myocardial infarction was not prevented by surgical reperfusion or medical therapy (23% in both groups), however, the mortality rate in patients with recurrent infarction was higher in the medical therapy group--36.6% (15 of 41) versus 17.5% (7 of 40) (p = 0.04). The mortality difference did not depend on early or late surgical reperfusion. In the in-hospital survivors, the incidence of sudden death was 17.5% in the medical (31 of 177) versus 7.4% (13 of 176) in the surgical group (p = 0.01). This difference was much more pronounced in the early reperfusion group. Functional class was significantly lower than that for medical therapy in the early reperfusion but not the late reperfusion group. Thus, in comparable groups given medical and surgical therapy for acute myocardial infarction and followed up for greater than or equal to 10 years, surgical reperfusion appears to offer improved longevity in selected cases (when implemented early) but does not prevent recurrent myocardial infarction. The associated mortality with recurrent myocardial infarction is less as is the incidence of sudden death. Finally, lower functional class occurs most often in patients given early reperfusion.

Medical and surgical management of early Q wave myocardial infarction. II. Effects on mortality and global and regional left ventricular function at 10 or more years of follow-up.

To determine the long-term effect of surgical reperfusion on survival and left ventricular function of patients with anterior and inferior Q wave myocardial infarction, 387 patients were followed up for greater than or equal to 10 years after early Q wave infarction. In the anterior infarction group, 102 received conventional therapy and 101 underwent surgical reperfusion. The overall hospital mortality rate in the medically and surgically treated patients was different (16.7% [17 of 102] versus 6.9% [7 of 101], p less than 0.05). The cumulative 13 year actuarial mortality rate widened between the anterior medical and surgical groups (54% versus 31%, p = 0.0003) by the adjusted Cox proportional hazards model. The hospital mortality rate with early reperfusion (that is, less than or equal to 6 h of symptom onset) was 2% (1 of 51), whereas the mortality rate with late reperfusion was 12% (6 of 50). The 13 year actuarial cumulative mortality rate was significantly lower in both the early and late reperfusion groups (30% and 33%, respectively) than in the conventional therapy group (54%, p = 0.0006). The mortality rate in patients receiving surgery after surviving initial medical therapy was 50% (15 of 30). In the survivors of anterior Q wave myocardial infarction, improved global ejection fraction was seen in the patients undergoing early (54 +/- 13%) and late (50 +/- 10%) surgery relative to those receiving conventional therapy (43 +/- 11%, p less than 0.05). Only the early reperfusion group had better regional function of the anterior wall than that of the conventional therapy group. Thus, ventricular function correlated with improved long-term survival. In the patients with inferior Q wave myocardial infarction, the overall hospital mortality rate in the medical and surgical groups was not different (6.1% [6 of 98] versus 4.6% [6 of 86], p = NS). Likewise, the 13 year actuarial cumulative mortality rate was not different between the medical and surgical groups overall (32% versus 30%, p = 0.29) by the adjusted Cox proportional hazards model. The hospital mortality rate in the early reperfusion group was lower than that in the late reperfusion group (2.0% [1 of 49] versus 8.1% [3 of 37], p = NS). The 13 year actuarial cumulative mortality rate was lower in the early surgical group compared with that in the medical group (19% versus 32%, p = 0.04). The late surgical group had a similar 13 year actuarial cumulative mortality rate to that of the medical group (47% versus 32%, respectively, p = 0.47).(ABSTRACT TRUNCATED AT 400 WORDS)

The efficacy of the addition of nifedipine in patients with mixed angina compared to patients with classic exertional angina: a multicenter, randomized, double-blind, placebo-controlled clinical trial.

Episodes of myocardial ischemia in patients with coronary artery disease may be due to transient increases in coronary vasomotor tone superimposed on a fixed atherosclerotic obstruction. The purpose of this study was to determine whether identification of the clinical pattern of angina could predict the therapeutic response to the addition of nifedipine to a regimen of beta blockers and/or long-acting nitrates. Seventy-two patients with stable exertional angina were divided into two groups: "classic exertional angina" (17 patients), defined as exertional angina with a stable threshold; and "mixed angina" (55 patients), defined as exertional angina provoked by a variable threshold and/or at least two episodes of rest angina within the 3 months prior to screening. Patients were studied with nifedipine and placebo in a 6-week, double-blind, crossover design that used serial anginal diaries, exercise treadmill tests, and 24-hour ambulatory ECG monitoring. In patients with mixed angina, nifedipine reduced the frequency of angina compared to that during placebo treatment (13.1 vs 9.9 episodes/3 weeks, p less than 0.01) and reduced nitroglycerin consumption (11.7 vs 7.5 tablets/3 weeks, p less than 0.05); while in patients with classic exertional angina, nifedipine had no symptomatic effect (7.9 vs 6.8 anginal episodes/3 weeks, NS; 6.4 vs 5.8 nitroglycerin tablets/3 weeks, NS). Patients in both groups experienced a significant decrease in the manifestations of ischemia during exercise testing. Patients with mixed angina experienced a reduction in the daily frequency of painful episodes of ST segment depression during nifedipine treatment compared to placebo (0.6 vs 0.2 episodes, p less than 0.05), but there was no effect on the frequency of episodes of silent ischemia (4.2 vs 3.4 episodes, NS). In patients with classic exertional angina, the addition of nifedipine had no effect on any measure of ambulatory ischemia. We conclude that patients with mixed angina are more likely to benefit symptomatically from the addition of nifedipine therapy than patients with classic exertional angina. The lack of a consistently preferential response to nifedipine in patients with mixed angina, however, suggests that episodic coronary vasoconstriction may not be the only mechanism responsible for ischemia in these patients, and/or that nifedipine may not necessarily provide additional therapeutic benefit beyond that conferred by a regimen of beta blockers and/or nitrates.

Clinical implications of coronary arteriographic findings soon after non-Q-wave acute myocardial infarction.

A significant incidence of death and myocardial infarction after non-Q-wave infarction belies the earlier impression that it is less serious than Q-wave infarction. Coronary angiography in the early stages after non-Q-wave infarction shows a progressive increase in the number of totally occluded vessels. This is paralleled by an increase in number of collateral vessels. Thrombus also becomes increasingly prevalent over the week after non-Q-wave infarction, and plays a role in 30 to 40% of infarctions.