Effect of captopril on mortality and morbidity in patients with left ventricular dysfunction after myocardial infarction. results of the survival and ventricular enlargement trial
Harvard University1, University of Texas Health Science Center at Houston2, Stony Brook University3, University of Manitoba4, Washington University in St. Louis5, University of Arizona6, University of Missouri7, Université de Montréal8, Icahn School of Medicine at Mount Sinai9, Laval University10, Yeshiva University11
03 Sep 1992-The New England Journal of Medicine (Massachussetts Medical Society)-Vol. 327, Iss: 10, pp 669-677
TL;DR: In patients with asymptomatic left ventricular dysfunction after myocardial infarction, long-term administration of captopril was associated with an improvement in survival and reduced morbidity and mortality due to major cardiovascular events.
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...
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Boston University1, Rush University Medical Center2, University of Tennessee Health Science Center3, University of Michigan4, University at Buffalo5, University of Mississippi6, University of Miami7, University of Alabama at Birmingham8, Case Western Reserve University9, National Institutes of Health10
TL;DR: The most effective therapy prescribed by the most careful clinician will control hypertension only if patients are motivated, and empathy builds trust and is a potent motivator.
Abstract: "The Seventh Report of the Joint National Committee on Prevention, Detection,
Evaluation, and Treatment of High Blood Pressure" provides a new guideline
for hypertension prevention and management. The following are the key messages(1) In persons older than 50 years, systolic blood pressure (BP) of
more than 140 mm Hg is a much more important cardiovascular disease
(CVD) risk factor than diastolic BP; (2) The risk of CVD, beginning at 115/75
mm Hg, doubles with each increment of 20/10 mm Hg; individuals who are normotensive
at 55 years of age have a 90% lifetime risk for developing hypertension; (3)
Individuals with a systolic BP of 120 to 139 mm Hg or a diastolic BP of 80
to 89 mm Hg should be considered as prehypertensive and require health-promoting
lifestyle modifications to prevent CVD; (4) Thiazide-type diuretics should
be used in drug treatment for most patients with uncomplicated hypertension,
either alone or combined with drugs from other classes. Certain high-risk
conditions are compelling indications for the initial use of other antihypertensive
drug classes (angiotensin-converting enzyme inhibitors, angiotensin-receptor
blockers, β-blockers, calcium channel blockers); (5) Most patients with
hypertension will require 2 or more antihypertensive medications to achieve
goal BP (<140/90 mm Hg, or <130/80 mm Hg for patients with diabetes
or chronic kidney disease); (6) If BP is more than 20/10 mm Hg above goal
BP, consideration should be given to initiating therapy with 2 agents, 1 of
which usually should be a thiazide-type diuretic; and (7) The most effective
therapy prescribed by the most careful clinician will control hypertension
only if patients are motivated. Motivation improves when patients have positive
experiences with and trust in the clinician. Empathy builds trust and is a
potent motivator. Finally, in presenting these guidelines, the committee recognizes
that the responsible physician's judgment remains paramount.
24,988 citations
TL;DR: In those older than age 50, systolic blood pressure of greater than 140 mm Hg is a more important cardiovascular disease (CVD) risk factor than diastolic BP, and hypertension will be controlled only if patients are motivated to stay on their treatment plan.
Abstract: The National High Blood Pressure Education Program presents the complete Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure. Like its predecessors, the purpose is to provide an evidence-based approach to the prevention and management of hypertension. The key messages of this report are these: in those older than age 50, systolic blood pressure (BP) of greater than 140 mm Hg is a more important cardiovascular disease (CVD) risk factor than diastolic BP; beginning at 115/75 mm Hg, CVD risk doubles for each increment of 20/10 mm Hg; those who are normotensive at 55 years of age will have a 90% lifetime risk of developing hypertension; prehypertensive individuals (systolic BP 120-139 mm Hg or diastolic BP 80-89 mm Hg) require health-promoting lifestyle modifications to prevent the progressive rise in blood pressure and CVD; for uncomplicated hypertension, thiazide diuretic should be used in drug treatment for most, either alone or combined with drugs from other classes; this report delineates specific high-risk conditions that are compelling indications for the use of other antihypertensive drug classes (angiotensin-converting enzyme inhibitors, angiotensin-receptor blockers, beta-blockers, calcium channel blockers); two or more antihypertensive medications will be required to achieve goal BP (<140/90 mm Hg, or <130/80 mm Hg) for patients with diabetes and chronic kidney disease; for patients whose BP is more than 20 mm Hg above the systolic BP goal or more than 10 mm Hg above the diastolic BP goal, initiation of therapy using two agents, one of which usually will be a thiazide diuretic, should be considered; regardless of therapy or care, hypertension will be controlled only if patients are motivated to stay on their treatment plan. Positive experiences, trust in the clinician, and empathy improve patient motivation and satisfaction. This report serves as a guide, and the committee continues to recognize that the responsible physician's judgment remains paramount.
14,975 citations
TL;DR: Authors/Task Force Members: Piotr Ponikowski* (Chairperson) (Poland), Adriaan A. Voors* (Co-Chair person) (The Netherlands), Stefan D. Anker (Germany), Héctor Bueno (Spain), John G. F. Cleland (UK), Andrew J. S. Coats (UK)
13,400 citations
TL;DR: In this article, Anderson et al. proposed a new FAHA Chair, Jeffrey L. Anderson, MD, FACC, FAHA, Chair-Elect, Alice K. Jacobs et al., this article and Biykem Bozkurt.
11,386 citations
TL;DR: Ramipril significantly reduces the rates of death, myocardial infarction, and stroke in a broad range of high-risk patients who are not known to have a low ejection fraction or heart failure.
Abstract: Angiotensin-converting-enzyme inhibitors improve the outcome among patients with left ventricular dysfunction, whether or not they have heart failure. We assessed the role of an angiotensin-converting-enzyme inhibitor, ramipril, in patients who were at high risk for cardiovascular events but who did not have left ventricular dysfunction or heart failure.A total of 9297 high-risk patients (55 years of age or older) who had evidence of vascular disease or diabetes plus one other cardiovascular risk factor and who were not known to have a low ejection fraction or heart failure were randomly assigned to receive ramipril (10 mg once per day orally) or matching placebo for a mean of five years. The primary outcome was a composite of myocardial infarction, stroke, or death from cardiovascular causes. The trial was a two-by-two factorial study evaluating both ramipril and vitamin E. The effects of vitamin E are reported in a companion paper.A total of 651 patients who were assigned to receive ramipril (14.0 percent) reached the primary end point, as compared with 826 patients who were assigned to receive placebo (17.8 percent) (relative risk, 0.78; 95 percent confidence interval, 0.70 to 0.86; P<0.001). Treatment with ramipril reduced the rates of death from cardiovascular causes (6.1 percent, as compared with 8.1 percent in the placebo group; relative risk, 0.74; P<0.001), myocardial infarction (9.9 percent vs. 12.3 percent; relative risk, 0.80; P<0.001), stroke (3.4 percent vs. 4.9 percent; relative risk, 0.68; P<0.001), death from any cause (10.4 percent vs. 12.2 percent; relative risk, 0.84; P=0.005), revascularization procedures (16.3 percent vs. 18.8 percent; relative risk, 0.85; P<0.001), cardiac arrest (0.8 percent vs. 1.3 percent; relative risk, 0.62; P=0.02), [corrected] heart failure (9.1 percent vs. 11.6 percent; relative risk, 0.77; P<0.001), and complications related to diabetes (6.4 percent vs. 7.6 percent; relative risk, 0.84; P=0.03).Ramipril significantly reduces the rates of death, myocardial infarction, and stroke in a broad range of high-risk patients who are not known to have a low ejection fraction or heart failure.
7,828 citations
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9,803 citations
TL;DR: The addition of enalapril to conventional therapy significantly reduced mortality and hospitalizations for heart failure in patients with chronic congestive heart failure and reduced ejection fractions.
Abstract: Background Patients with congestive heart failure have a high mortality rate and are also hospitalized frequently. We studied the effect of an angiotensin-converting-enzyme inhibitor, enalapril, on mortality and hospitalization in patients with chronic heart failure and ejection fractions less than or equal to 0.35. Methods Patients receiving conventional treatment for heart failure were randomly assigned to receive either placebo (n = 1284) or enalapril (n = 1285) at doses of 2.5 to 20 mg per day in a double-bind trial. Approximately 90 percent of the patients were in New York Heart Association functional classes II and III. The follow-up averaged 41.4 months. Results There were 510 deaths in the placebo group (39.7 percent), as compared with 452 in the enalapril group (35.2 percent) (reduction in risk, 16 percent; 95 percent confidence interval, 5 to 26 percent; P = 0.0036). Although reductions in mortality were observed in several categories of cardiac deaths, the largest reduction occurred among the deaths attributed to progressive heart failure (251 in the placebo group vs. 209 in the enalapril group; reduction in risk, 22 percent; 95 percent confidence interval, 6 to 35 percent). There was little apparent effect of treatment on deaths classified as due to arrhythmia without pump failure. Fewer patients died or were hospitalized for worsening heart failure (736 in the placebo group and 613 in the enalapril group; risk reduction, 26 percent; 95 percent confidence interval, 18 to 34 percent; P less than 0.0001). Conclusions The addition of enalapril to conventional therapy significantly reduced mortality and hospitalizations for heart failure in patients with chronic congestive heart failure and reduced ejection fractions.
7,460 citations
TL;DR: The extent of ventricular enlargement after infarction is related to the magnitude of the initial damage to the myocardium and, although an increase in cavity size tends to restore stroke volume despite a persistently depressed ejection fraction, ventricular dilation has been associated with a reduction in survival.
Abstract: An acute myocardial infarction, particularly one that is large and transmural, can produce alterations in the topography of both the infarcted and noninfarcted regions of the ventricle. This remodeling can importantly affect the function of the ventricle and the prognosis for survival. In the early period, infarct expansion has been recognized by echocardiography as a lengthening of the noncontractile region. The noninfarcted region also undergoes an important lengthening that is consistent with a secondary volume-overload hypertrophy and that can be progressive. The extent of ventricular enlargement after infarction is related to the magnitude of the initial damage to the myocardium and, although an increase in cavity size tends to restore stroke volume despite a persistently depressed ejection fraction, ventricular dilation has been associated with a reduction in survival. The process of ventricular enlargement can be influenced by three interdependent factors, that is, infarct size, infarct healing, and ventricular wall stresses. A most effective way to prevent or minimize the increase in ventricular size after infarction and the consequent adverse effect on prognosis is to limit the initial insult. Acute reperfusion therapy has been consistently shown to result in a reduction in ventricular volume. The reestablishment of blood flow to the infarcted region, even beyond the time frame for myocyte salvage, has beneficial effects in attenuating ventricular enlargement. The process of scarification can be interfered with during the acute infarct period by the administration of glucocorticosteroids and nonsteroidal antiinflammatory agents, which result in thinner infarcts and greater degrees of infarct expansion. Modification of distending or deforming forces can importantly influence ventricular enlargement. Even short-term augmentations in afterload have deleterious long-term effects on ventricular topography. Conversely, judicious use of nitroglycerin seems to be associated with an attenuation of infarct expansion and long-term improvement in clinical outcome. Long-term therapy with an angiotensin converting enzyme inhibitor can favorably alter the loading conditions on the left ventricle and reduce progressive ventricular enlargement as demonstrated in both experimental and clinical studies. With the former therapy, this attenuation of ventricular enlargement was associated with a prolongation in survival. The long-term clinical consequences of long-term angiotensin converting enzyme inhibitor therapy after myocardial infarction is currently being evaluated. Although studies directed at attenuating left ventricular remodeling after infarction are in the early stages, it does seem that this will be an important area in which future research might improve long-term outcome after infarction.
2,815 citations
TL;DR: Volume, ejection fractions, and severity of coronary arterial occlusions and stenoses in 605 male patients under 60 years of age at 1 to 2 months after a first or recurrent myocardial infarction showed that end-systolic volume had greater predictive value for survival than end-diastolic volume or ejection fraction.
Abstract: Impairment of left ventricular function is the major predictor of mortality after acute myocardial infarction, but it is not known whether this is best described by ejection fraction or by end-systolic or end-diastolic volume. We measured volumes, ejection fractions, and severity of coronary arterial occlusions and stenoses in 605 male patients under 60 years of age at 1 to 2 months after a first (n = 443) or recurrent (n = 162) myocardial infarction and followed these patients for a mean of 78 months for survivors (range 15 to 165 months). There were 101 cardiac deaths, 71 (70%) of which were sudden (instantaneous or found dead). Multivariate analysis with log rank testing and the Cox proportional hazards model showed that end-systolic volume (chi 2 = 82.9) had greater predictive value for survival than end-diastolic volume (chi 2 = 59.0) or ejection fraction (chi 2 = 46.6), whereas stepwise analysis showed that once the relationship between survival and end-systolic volume had been fitted, there was no additional significant predictive information in either end-diastolic volume or ejection fraction. Severity of coronary occlusions and stenoses showed additional prediction of only borderline significance (p = .04 in one analysis), but continued cigarette smoking did remain an independent risk factor after stepwise analysis. For a subset of patients (n = 200) who had taken part in a randomized trial of coronary artery surgery after recovery from infarction, surgical "intention to treat" showed no predictive value.(ABSTRACT TRUNCATED AT 250 WORDS)
2,305 citations
TL;DR: The data suggest that the addition of hydralazine and isosorbide dinitrate to the therapeutic regimen of digoxin and diuretics in patients with chronic congestive heart failure can have a favorable effect on left ventricular function and mortality.
Abstract: To evaluate the effects of vasodilator therapy on mortality among patients with chronic congestive heart failure, we randomly assigned 642 men with impaired cardiac function and reduced exercise tolerance who were taking digoxin and a diuretic to receive additional double-blind treatment with placebo, prazosin (20 mg per day), or the combination of hydralazine (300 mg per day) and isosorbide dinitrate (160 mg per day). Follow-up averaged 2.3 years (range, 6 months to 5.7 years). Mortality over the entire follow-up period was lower in the group that received hydralazine and isosorbide dinitrate than in the placebo group. This difference was of borderline statistical significance. For mortality by two years, a major end point specified in the protocol, the risk reduction among patients treated with both hydralazine and isosorbide dinitrate was 34 percent (P less than 0.028). The cumulative mortality rates at two years were 25.6 percent in the hydralazine--isosorbide dinitrate group and 34.3 percent in the placebo group; at three years, the mortality rate was 36.2 percent versus 46.9 percent. The mortality-risk reduction in the group treated with hydralazine and isosorbide dinitrate was 36 percent by three years. The mortality in the prazosin group was similar to that in the placebo group. Left ventricular ejection fraction (measured sequentially) rose significantly at eight weeks and at one year in the group treated with hydralazine and isosorbide dinitrate but not in the placebo or prazosin groups. Our data suggest that the addition of hydralazine and isosorbide dinitrate to the therapeutic regimen of digoxin and diuretics in patients with chronic congestive heart failure can have a favorable effect on left ventricular function and mortality.
2,184 citations