Showing papers by "Eugene Braunwald published in 1992"

Effect of captopril on mortality and morbidity in patients with left ventricular dysfunction after myocardial infarction. results of the survival and ventricular enlargement trial

Abstract: Background. Left ventricular dilatation and dysfunction after myocardial infarction are major predictors of death. In experimental and clinical studies, long-term therapy with the angiotensin-converting—enzyme inhibitor captopril attenuated ventricular dilatation and remodeling. We investigated whether captopril could reduce morbidity and mortality in patients with left ventricular dysfunction after a myocardial infarction. Methods. Within 3 to 16 days after myocardial infarction, 2231 patients with ejection fractions of 40 percent or less but without overt heart failure or symptoms of myocardial ischemia were randomly assigned to receive double-blind treatment with either placebo (1116 patients) or captopril (1115 patients) and were followed for an average of 42 months. Results. Mortality from all causes was significantly reduced in the captopril group (228 deaths, or 20 percent) as compared with the placebo group (275 deaths, or 25 percent); the reduction in risk was 19 percent (95 percent conf...

Predictors of early morbidity and mortality after thrombolytic therapy of acute myocardial infarction. Analyses of patient subgroups in the Thrombolysis in Myocardial Infarction (TIMI) trial, phase II.

Abstract: BACKGROUNDThrombolysis has altered treatment of acute myocardial infarction (AMI). Therefore, reevaluation of predictors of outcome and treatment strategies is appropriate.METHODS AND RESULTSClinical variables collected prospectively for the 3,339 patients of the Thrombolysis in Myocardial Infarction II study were analyzed retrospectively to identify predictors of clinical events at 42 days and earlier and to identify subgroups in which an invasive or conservative strategy might be superior. Pulmonary edema/cardiogenic shock presented as the strongest independent correlate with death (relative risk, 6.0). In two subgroups, mortality differed between the invasive and conservative strategies: 1) Patients with versus without prior AMI had a higher mortality in the conservative strategy (11.5% versus 3.5%, p less than 0.001); in the invasive strategy, the mortality rates were similar (6.0% and 5.1%). 2) Patients with diabetes mellitus and no prior AMI had a higher mortality in the invasive than in the conserv...

Do the Results of Randomized Clinical Trials of Cardiovascular Drugs Influence Medical Practice

Abstract: Background. Medical practice patterns change in response to a variety of stimuli, one of which may be the publication of the results of randomized clinical trials. We assessed the temporal association between the publication of clinical trials on myocardial infarction and changes in treatment practices for this disorder. Methods. We analyzed the use of aspirin before and after myocardial infarction and that of calcium antagonists after myocardial infarction in 2231 survivors of myocardial infarction enrolled in the Survival and Ventricular Enlargement (SAVE) study over a three-year period (from January 1987 through January 1990). The proportion of patients using these treatments was analyzed before and after the publication dates of three clinical trials: the Physicians' Health Study, published in January 1988, which supported the use of aspirin to prevent a first myocardial infarction; the Second International Study of Infarct Survival (ISIS-2), published in August 1988, which supported the use ...

Cholesterol and total mortality: need for larger trials.

Abstract: EDITOR,-It has been suggested that the current trials of 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors can be expected to provide reliable evidence on the effects of lowering blood cholesterol concentration on total mortality.' Those trials are, however, designed primarily to assess the effects oflowering cholesterol concentration only on coronary heart disease. Consequently, they have limited ability to detect the sort of effects on total mortality that it is realistic to hope for, except perhaps in the special circumstance of patients who have already suffered a myocardial infarction, among whom nearly all deaths are due to coronary heart disease. But this special circumstance of \"secondary\" prevention includes only a fraction of the wide range of people who have a moderately raised risk of coronary heart disease and for whom reliable evidence is needed about the efficacy, safety, and overall effects of reducing cholesterol concentration. Moreover, if reducing cholesterol concentration has any real effects on mortality from causes other than coronary heart disease these need to be recognised, as they could be of substantial relevance not only to patients but also to the general population. In considering total mortality, suppose that in the current trials cholesterol lowering has no material effect on deaths from causes other than coronary heart disease and, as is suggested by previous trials,23 that there is a roughly one to one relation between the percentage reduction in cholesterol concentration and the percentage reduction in deaths from coronary heart disease during a trial lasting five or six years (so that a 20% reduction in cholesterol would lower mortality from coronary heart disease in a five year trial by about 20%). The table shows the numbers of deaths from all causes that would then be expected and the statistical power of the current trials to detect such reductions in total mortality. Taken separately from each other, even the studies of secondary prevention among patients after myocardial infarction may well fail to show the sort of effects on total mortality that might realistically be expected (table). Combining all their results in a systematic overview (or metaanalysis4) should allow such an effect on total mortality to be detected, but there is still a material chance that it might fail to be. And, even if the overall results were significant, there would almost certainly be some major subgroup (for example, men or women, young or old, moderately or extremely raised cholesterol concentration) in which ambiguous results would lead to prolonged dispute-especially since an overview of several results may not be as convincing to some clinicians as a single trial of adequate size.5 6 The situation is much worse in the primary prevention of myocardial infarction among people at high risk of coronary heart disease, among whom a larger proportion ofdeaths are from causes other than coronary heart disease. For even an overview of the studies of primary prevention currently under way may fail to show the expected reductions in fatal coronary heart disease, let alone any effects on total mortality (table). Moreover, for primary as for secondary prevention, the power calculations for the current trials relate only to the overall results: if any subgroups (for example, men or women, middle aged or old) are to be analysed separately to help determine which patients need treatment then the power of the individual trials (and of any overview) is further reduced. It might have been hoped that the current trials would at least be able to address reliably the suggestion that lowering cholesterol concentration results in an increase in deaths from causes other than coronary heart disease, but this too is uncertain. In assessing any potential hazards of lowering cholesterol concentration the power of the trials depends on the numbers of deaths from causes other than coronary heart disease. Overall in the current trials only about 600 such deaths are expected, of which one third might be from cancer and one sixth from external causes such as accidents, violence, and suicide. Even a meta-analysis of all these studies would have less than a one in three chance of detecting (or excluding) the sort of increases in deaths from all causes other than coronary heart disease (of about 20%), from cancer (of about 30%), and from external causes (of about 50%) suggested by some reviewers of the previous cholesterol lowering trials.' There is therefore a substantial risk of false negative results for total mortality from these trials and of equivocal evidence about any effects of lowering cholesterol concentrations on causes of death other than coronary heart disease (such as cancer). This underlines the need for further large studies which, taken together with the results from the current trials, could answer these questions more reliably. Such evidence would not just be relevant to drug treatment for a wide range of people at increased risk of coronary heart disease but also help, indirectly, to resolve the long running controversy about the public health importance of lowering cholesterol concentrations by dietary means.

An approach to evaluating thrombolytic therapy in acute myocardial infarction. The 'unsatisfactory outcome' end point.

Abstract: T he primary goal of thrombolytic therapy in acute myocardial infarction (AMI) is the early restoration of perfusion and maintenance of viability and function of myocardium that would otherwise undergo necrosis consequent to thrombotic coronary artery occlusion. The salvage achieved by thrombolysis ranges from a minute amount of myocardium of little functional significance to a large mass of heart muscle the necrosis of which could cause death, with an intermediate quantity in most patients. The most dramatic outcome of thrombolytic therapy is reduced in-hospital mortality,'-4 but early mortality is a relatively crude end point for measuring variations in the extent to which a given regimen accomplishes the primary goal of thrombolytic therapy defined above. Successful thrombolytic therapy also reduces the frequency of serious complications of AMI such as congestive heart failure and cardiogenic shock.5 Laboratory measurements reflecting benefit include preservation of left ventricular function and the early reestablishment and subsequent maintenance of patency of the infarct-related coronary artery. The favorable outcome of thrombolytic therapy is in some instances offset by recurrent infarction and by adverse effects, e.g., severe bleeding, including the most serious of all complications hemorrhagic stroke. These other (nonfatal) outcomes should also be taken into account in assessing thrombolytic therapy. The favorable effects of thrombolytic therapy have been clearly demonstrated in placebo-controlled trials, and when laboratory measurements such as coronary artery patency or left ventricular function are taken as end points, benefit can be shown in studies comprising only several dozen or a few hundred patients.5-10 To compare the effects of thrombolytic therapy and placebo on survival, however, trials involving several thousands of patients for each are required.1-4 With the exception of special groups of patients, such as those with ST segment depression and those who present relatively late, i.e., more than 6 hours after the onset of symptoms, the benefits of thrombolytic therapy on survival have now been so clearly established that placebocontrolled trials are no longer needed, nor would they

Assessment of global and regional left ventricular performance at rest and during exercise after thrombolytic therapy for acute myocardial infarction: results of the Thrombolysis in Myocardial Infarction (TIMI) II Study.

Abstract: Global and regional left ventricular performances were evaluated with equilibrium radionuclide angiocardiography in patients in the Thrombolysis in Myocardial Infarction (TIMI) II trial at the time of hospital discharge. Studies at rest were available in 1,162 (69%) of the invasive and 1,150 (69%) of the conservative strategy patients, and exercise studies in 1,133 (67%) of the invasive and 1,145 (69%) of the conservative patients. Repeat studies were performed at the time of 6-week follow-up. Global and regional ejection fraction at rest were both comparable in patients assigned to each of the treatment strategies. However, at the time of hospital discharge patients in the invasive strategy had normal exercise responses more frequently (29.7 vs 25.8% p = 0.01), greater peak exercise LV ejection fraction (54.8 +/- 13.8% vs 53.1 +/- 14.1%, p = 0.004), greater exercise--rest change in LV ejection fraction (3.7 +/- 6.7% vs 2.7 +/- 7.2%, p less than 0.001) and greater peak exercise infarct zone regional ejection fraction (53.2 +/- 31.1% vs 50.3 +/- 33.0%, p less than 0.001) than patients assigned to the conservative strategy. At 6-week follow-up these differences between treatment strategies were no longer evident. When data were restricted to those collected at comparable work loads, similar differences in hospital discharge exercise performance between invasive vs conservative strategy patients were observed. Thus, there is a small transient difference in exercise global and regional LV performance associated with an invasive as opposed to conservative strategy after thrombolytic therapy. These differences are noted at the time of hospital discharge but not at 6 weeks, and are unlikely to confer clinical benefit.

Myocardial Stunning and Hibernation: Mechanisms and Clinical Implication

Abstract: The purpose of this article is to review the concepts of myocardial stunning and hibernation. Stunned myocardium is defined as viable myocardium that exhibits prolonged postischemic dysfunction. This phenomenon has been observed both in experimental animal models and, more recently, in man. Examples in patients include slow recovery of regional wall motion abnormalities following thrombolytic therapy for acute myocardial infarction, and persistent regional wall motion abnormalities observed following exercise induced ischemia. Potential mechanism for stunned myocardium include alterations in calcium homeostasis and oxygen free radical damage.

Methods for reducing risk of repeat myocardial infarction and increasing survival in heart attack victims

Abstract: The invention involves a method for treating a human survivor of a heart attack and provides further improvement in survival following the heart attack by the early initiation and long-term administration of a renin-angiotensin system inhibitor, preferably an angiotensin converting enzyme inhibitor. The inhibitor may be used on its own, or in conjunction with other therapeutic compounds such as data blockers and thrombolytic agents. The preferred inhibitor is captopril.

Captopril for left ventricular dysfunction after myocardial infarction

Abstract: Source Citation Pfeffer MA, Braunwald E, Moye LA, et al. Effect of captopril on mortality and morbidity in patients with left ventricular dysfunction after myocardial infarction. Results of the Sur...