Showing papers by "Marc A. Pfeffer published in 1995"
TL;DR: The presence of the D allele of the ACE gene conferred no appreciable increase in the risk of ischemic heart disease or myocardial infarction in a large, prospectively followed population of U.S. male physicians.
Abstract: Background In a previous study, men with a history of myocardial infarction were found to have an increased prevalence of homozygosity for the deletional allele (D) of the angiotensin-converting–enzyme (ACE) gene. The D allele is associated with higher levels of ACE, which may predispose a person to ischemic heart disease. We investigated the association between the ACE genotype and the incidence of myocardial infarction, as well as other manifestations of ischemic heart disease, in a large, prospective cohort of U.S. male physicians. Methods In the Physicians' Health Study, ischemic heart disease as defined by angina, coronary revascularization, or myocardial infarction developed in 1250 men by 1992. They were matched with 2340 controls according to age and smoking history. Zygosity for the deletion–insertion (D–I) polymorphism of the ACE gene was determined by an assay based on the polymerase chain reaction. Data were analyzed for both matched pairs and unmatched samples, with adjustment for the effects...
922 citations
TL;DR: Increasing clinical evidence indicates that this new use of ACE inhibitor therapy in survivors of acute myocardial infarction will lead to an improvement in clinical outcome.
Abstract: ▪ Abstract The loss of myocytes as a consequence of myocardial infarction results in a prompt reduction in regional wall motion and often leads to more protracted and progressive changes in ventricular architecture. The recognition that the process of ventricular enlargement following myocardial infarction is modifiable provided the initial rationale for the use of angiotensin-converting enzyme (ACE) inhibitors as therapy to prevent deterioration in ventricular size and function following infarction. Experimental and clinical studies have documented the effectiveness of this therapy in preventing this late enlargement following infarction. Increasing clinical evidence indicates that this new use of ACE inhibitor therapy in survivors of acute myocardial infarction will lead to an improvement in clinical outcome.
253 citations
TL;DR: Findings support the need for additional, prospective clinical trials of late reperfusion in MI patients and determine the effect of angiotensin-converting enzyme (ACE) inhibitor therapy on patients with patent as well as occluded infarct arteries.
Abstract: Background In patients with acute myocardial infarction (MI), early restoration of patency of the infarct-related artery (IRA) leads to preservation of left ventricular function and improved clinical outcome. However, there is evidence that the benefits associated with a patent IRA are out of proportion to the observed improvement in ventricular function and may result not only from salvage of ischemic myocardium but also from the opening of the IRA beyond a narrow postinfarct time window. The objectives of this study were (1) to assess the effect of IRA patency on outcome of patients after acute MI with left ventricular dysfunction while controlling for differences in left ventricular ejection fraction and the extent of coronary disease and (2) to determine the effect of angiotensin-converting enzyme (ACE) inhibitor therapy on patients with patent as well as occluded infarct arteries. Methods and Results The Survival and Ventricular Enlargement (SAVE) study consisted of 2231 patients with a documented MI...
198 citations
TL;DR: Two distinct arrhythmogenic periods occur in rats with acute MI that may be caused by different mechanisms and correspond to the bimodal arrhythmia time course seen in dogs and humans after acute MI.
Abstract: Background The onset of acute myocardial infarction (MI) is accompanied by a rapid increase in electrical instability and often fatal ventricular arrhythmias. The aim of this study was to assess the continuous arrhythmia profile during the initial 48 hours after coronary artery ligation in the rat in relation to time course, mortality, and infarct size. Methods and Results Continuous ECG recordings were obtained in 26 conscious, untethered rats for 24 hours before and 48 hours after coronary ligation by use of an implantable telemetry system. All episodes of ventricular tachycardia and fibrillation were counted and their durations summed. Infarct size was measured at 48 hours after MI or after spontaneous death. After ligation, two distinctly active arrhythmogenic periods developed (A1, 0 to 0.5 hours; A2, 1.5 to 9 hours), each followed by a quiescent phase of low ectopy (Q1, 0.5 to 1.5 hours; Q2, 10 to 48 hours). The total mortality rate of 65% was found within the two active periods, with 13 of 15 death...
143 citations
132 citations
TL;DR: In this article, the authors used the 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitor pravastatin to reduce the sum of fatal coronary artery disease (CAD) and nonfatal myocardial infarction (Ml) in patients who have survived an Ml yet have a total cholesterol value.
Abstract: Although elevated plasma cholesterol levels represent a well-established and significant risk for developing atherosclerosis, there is a wide spectrum of cholesterol levels in patients with coronary artery disease (CAD). Most secondary prevention studies have generated convincing evidence that cholesterol reduction in patients with high cholesterol levels is associated with improved clinical outcome by reducing risk of further cardiovascular events. However, other risk factors may play a prominent role in the pathogenesis of coronary disease in the majority of patients with near-normal cholesterol values. The Cholesterol and Recurrent Events (CARE) study was designed to address whether the pharmacologic reduction of cholesterol levels with the 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitor, pravastatin, would reduce the sum of fatal coronary artery disease (CAD) and nonfatal myocardial infarction (Ml) in patients who have survived an Ml yet have a total cholesterol value
124 citations
TL;DR: The cost-effectiveness of captopril therapy for 50- to 80-year old survivors of myocardial infarction with a low ejection fraction compares favorably with other interventions for survivors of the disease.
114 citations
TL;DR: The objective of the trial was to establish both the range of anticipated benefits and the potential benefits of the drug and to establish the level of protection against adverse events.
Abstract: Any new therapeutic advance requires clear proof of effectiveness from well-designed and well-conducted clinical trials that establish both the range of anticipated benefits and the potential adver...
81 citations
Journal Article•
TL;DR: By establishing a register of ongoing and planned trials prior to any trial results being known, this systematic overview attempts to avoid the methodologic problems and potential data-dependency of a retrospective project.
Abstract: The Cholesterol Treatment Trialists' Collaboration aims to provide reliable information about the effects on mortality and morbidity of treatments that modify blood lipid levels for a wide range of patient populations and risk groups. This protocol prospectively defines study eligibility, the main questions to be addressed, and statistical methods to be used. Additionally, by establishing a register of ongoing and planned trials prior to any trial results being known, this systematic overview attempts to avoid the methodologic problems and potential data-dependency of a retrospective project. The collaboration expects to have individual patient data on > 60,000 subjects by the year 2000, including 12,000 women and 20,000 elderly subjects, and should have good power to examine any effects on non-coronary artery disease events. Overall, there should be about 1,900 non-coronary artery disease deaths and > 2,000 total cancer events.
76 citations
TL;DR: The results of CARE will have relevance to the treatment of the majority of patients with coronary disease who have average rather than elevated cholesterol levels.
Abstract: CARE will determine whether 5 years of cholesterol-lowering therapy reduces recurrent coronary disease events in 4,159 patients who have had an AMI. The mean total cholesterol and LDL-C levels in CARE (209 and 139 mg/dl) are similar to the average levels for the US population. The results of CARE will have relevance to the treatment of the majority of patients with coronary disease who have average rather than elevated cholesterol levels.
41 citations
TL;DR: This work has shown that pharmacological interruption of the RAS exerts a positive effect on endogenous fibrinolytic balance and this relationship appears to provide a partial explanation for the newly recognized effect of angiotensin converting enzyme inhibitors in preventing AMI.
Abstract: Activation of the renin-angiotensin system (RAS) has been implicated in the pathogenesis of acute myocardial infarction (AMI). Similarly, red ucedfibrinolytic activity has been associated with an increased risk of AMI. Evidence is now accumulating that the RAS plays an important role in the regulation offibrinolysis and that pharmacological interruption of the RAS exerts a positive effect on endogenousfibrinolytic balance. This relationship appears to provide a partial explanation for the newly recognized effect of angiotensin converting enzyme inhibitors in preventing AMI.
TL;DR: The rat model of coronary artery ligation is widely used to study myocardial infarction, ventricular remodeling, and congestive heart failure and infarct size indexed to endocardial incision size may represent a significantly more powerful method for assessing the effects of treatments to reduce infarCT size.
TL;DR: This study concurs with 2 of 3 previous post-AMI studies and supports the conclusion that working capacity is not affected by angiotensin-converting enzyme inhibition at 4 or 12 months after AMI in patients without congestive heart failure.
Abstract: Previous studies after acute myocardial infarction (AMI) have reported conflicting results on the effects of angiotensin-converting enzyme inhibition on physical working capacity. In an effort to provide more insight into this subject, we examined the effects of captopril on working capacity of patients who had low ejection fractions but no congestive heart failure after AMI. One hundred sixty-six participants were recruited from 5 centers after randomization to either captopril or placebo for the Survival and Ventricular Enlargement study. Upright cycle ergometer tests were performed with continuous measurements of respiratory gases at 4, 12, and 24 months after AMI. Our study concurs with 2 of 3 previous post-AMI studies and supports the conclusion that working capacity is not affected by angiotensin-converting enzyme inhibition at 4 or 12 months after AMI in patients without congestive heart failure. In addition, no significant effect of captopril was noted at 24 months after AMI. Peak oxygen uptake tended to decrease between 12 and 24 months in the placebo group by an average (+/- SD) of -22 +/- 322 ml/min (n = 66), but to increase in the captopril group (+62 +/- 289, n = 57), a difference that was significant (Mann-Whitney chi-square, p = 0.02). This post-hoc observation suggests that a late beneficial effect may have been masked by inadequate study duration. Known benefits of captopril appear not to include an increase in working capacity within the first 24 months after AMI.
TL;DR: Analysis of the role of regional and globalleft ventricular geometry in normal and abnormal ventricular function has broadened the undersatanding of the process of left ventricular remodeling after myocardial infarction.
Abstract: The left ventricular cahamber undergoes significant changes in volume and geometry after myocardial infarction, a process known as remodeling. The clinical importance of left ventricular remodeling after myocardial infraction has been established. Early after infraction the process of infant expansion may markedly increase ventricular volumes and distort ventricular geometry. This early distortion of regional geometry predisposes patient to late, progressive ventricular enlargement and development of heart failure, even in the absence of further ischemic envents. Analysis of the role of regional and global left ventricular geometry in normal and abnormal ventricular function has broadened our undersatanding of the process of left ventricular remodeling after myocardial infarction.
TL;DR: It is concluded that in the population-based sample of the Framingham Heart Study, there is no association between the ACE D-I polymorphism and level of LV mass or prevalence of LVH.
TL;DR: It is demonstrated that LV enlargement can occur in patients with patent IRAs, and there was a trend for less LV dilatation in captopril-treated patients.