Comparison of the effects of angiotensin converting-enzyme inhibitors and beta blockers on survival in elderly patients with reduced left ventricular function after myocardial infarction

PURPOSE: Angiotensin converting-enzyme (ACE) inhibitors decrease mortality after myocardial infarction among patients with depressed left ventricular function. Beta blockers may also improve survival in these patients. We compared the relative effects of these agents on the survival of elderly patients with a left ventricular ejection fraction less than 40% after myocardial infarction. SUBJECTS AND METHODS: The Cooperative Cardiovascular Project collected data on patients aged 65 years and older who were admitted with myocardial infarction from April 1994 to July 1995, including 20,902 with a measured left ventricular ejection fraction less than 40% before discharge. Using proportional hazard regression models that adjusted for patient characteristics and in-hospital treatments, we compared survival among patients discharged on ACE inhibitors, beta blockers, both medications, or neither medication. RESULTS: Among patients surviving hospitalization with reduced left ventricular function, 9,108 (44%) were discharged on ACE inhibitors, 2,613 (13%) on beta blockers, 3,309 (16%) on both medications, and 5,872 (28%) on neither medication. Patients treated with ACE inhibitors were more likely to have a prior diagnosis of heart failure and less likely to have undergone revascularization, whereas those treated with beta blockers were more often treated with thrombolytic therapy and aspirin. Patients treated with ACE inhibitors [hazard ratio (HR = 0.80), 0.80; 95% confidence interval (CI), 0.73 to 0.87] or beta blockers (HR = 0.76, 0.76; 95% CI, 0.64 to 0.90) had lower adjusted 1-year mortality than those who were not treated with either medication. The combination of both medications was associated with additional benefit (HR = 0.68, 0.68; 95% CI, 0.59 to 0.80). The relative benefit of each medication was greatest among patients with an ejection fraction less than 30%, a serum creatinine level 2.0 mg/dL or greater, or both. To prevent a death within a year, the number of patients who needed to be treated with both medications varied from 5 to 15, depending on ejection fraction and renal function. CONCLUSION: ACE inhibitors and beta blockers were associated with similar improvements in survival among elderly patients with reduced left ventricular ejection fraction after myocardial infarction. Our results suggest that patients who can tolerate both medications gain additional benefit from the combination.     

Should Angiotensin-Converting Enzyme Inhibitors Be Continued Over the Long Term in Patients Whose Left Ventricular Ejection Fraction Normalizes After an Episode of Acute Myocarditis?

It is well established that long-term administration of angiotensin-converting enzyme (ACE) inhibitors has a favorable effect in patients with chronic heart failure and dilated cardiomyopathy. However, less information is available on patients whose left ventricular ejection fraction normalizes after an episode of systolic dysfunction secondary to acute myocarditis. We followed 35 patients who were diagnosed at our center between 1987 and 1995 with acute myocarditis and an ejection fraction<45%. All were taking ACE inhibitors. After 34 (23) months of follow-up, the left ventricular ejection fraction was >50% in all 35 patients. Treatment with ACE inhibitors was discontinued in 15 of the 35 patients, while the other 20 continued ACE inhibitor therapy. After 3 years of follow-up, no death had occurred, but the incidence of new episodes of heart failure with a left ventricular ejection fraction<45% was higher in patients who stopped taking ACE inhibitors (33% vs 5%, P=.064), and their ejection fraction was lower (47 [12%] vs 57 [11%], P=.002). These results suggest that ACE inhibitors should be continued over the long term in these patients.     

A multivariate model for predicting mortality in patients with heart failure and systolic dysfunction

BACKGROUND: Heart failure is a leading cause of morbidity and mortality, but there are no reliable models based on readily available clinical variables to predict outcomes in patients taking angiotensin-converting enzyme (ACE) inhibitors. METHODS: A multivariate statistical model to predict mortality was developed in a random sample (n = 4277 patients [67%]) of the 6422 patients enrolled in the Digitalis Investigation Group trial who had a depressed ejection fraction (相似文献   

Contribution of left ventricular diastolic dysfunction to heart failure regardless of ejection fraction

Heart failure (HF) has been classified as systolic and diastolic based on the left ventricular ejection fraction. We hypothesized that left ventricular diastolic dysfunction is an important element of HF regardless of ejection fraction. Two hundred six patients who had clinical HF were compared with 72 age-matched controls. Diastolic dysfunction, as assessed by the mitral filling pattern and tissue Doppler imaging, was present in >90% of patients who had HF regardless of ejection fraction and was more frequent and severe than in age-matched controls (p <0.001). In patients who had HF, B-type natriuretic peptide correlated with diastolic dysfunction (r = 0.62, p <0.001) but not with ejection fraction or end-diastolic volume index (EDVI). The degree of diastolic dysfunction influenced survival rate (risk ratio 1.64, p <0.05), whereas ejection fraction and EDVI did not. Systolic function measured by systolic mitral annular velocity was decreased in patients who had HF and an ejection fraction /=0.50 (6.6 +/- 1.8 cm/s) compared with control subjects (8.0 +/- 2.1 cm/s, p <0.01). Patients who had HF and an ejection fraction >/=0.50 had an increased ratio of ventricular mass to EDVI. Patients who had HF and an ejection fraction /=0.50 is associated with mild systolic dysfunction and an increased ratio of left ventricular mass to EDVI. In HF with an ejection fraction 相似文献   

Utility of history, physical examination, electrocardiogram, and chest radiograph for differentiating normal from decreased systolic function in patients with heart failure

To determine whether clinical parameters alone can differentiate normal versus decreased systolic left ventricular function in patients with heart failure.Detailed clinical data were collected prospectively from 225 consecutive patients who were hospitalized with heart failure. Findings in patients with normal (ejection fraction > or =45%) or decreased (ejection fraction <45%) left ventricular function were compared.Systolic function was normal in 104 patients (46%) and decreased in 121 patients (54%). Patients with normal function were older (mean [+/- SD] age, 59 +/- 13 years vs. 54 +/- 13 years, P = 0.007) and more likely to be female (56% vs. 35%, P = 0.001), obese (body mass index > or =30 kg/m(2), 62% vs. 48%, P = 0.04), have marked systolic (> or =160 mm Hg, 50% vs. 27%, P <0.001) and diastolic (> or =110 mm Hg, 25% vs. 13%, P = 0.02) hypertension, and use calcium antagonists (34% vs. 14%, P = 0.001). Patients with decreased function were more likely to use alcohol (37% vs. 20%, P = 0.007), angiotensin-converting enzyme (ACE) inhibitors (85% vs. 62%, P <0.001), and digoxin (57% vs. 27%, P <0.001); and more likely to have tachycardia (51% vs. 32%, P = 0.004), rales (89% vs. 80%, P = 0.05), electrocardiographic left ventricular hypertrophy (42% vs. 22%, P = 0.002), left atrial abnormality (52% vs. 22%, P <0.001), or flow cephalization on chest radiograph (91% vs. 79%, P = 0.02). Only sex, tachycardia, and use of digoxin and ACE inhibitors were associated with ventricular function in multivariable analysis. However, the sensitivity, specificity, and predictive values for all clinical variables were low. Differences in clinical parameters in heart failure patients with decreased versus normal systolic function cannot predict systolic function in these patients, supporting recommendations that heart failure patients should undergo specialized testing to measure ventricular function.     

Clinical Characteristics,Left and Right Ventricular Ejection Fraction,and Long-term Prognosis in Patients with Non-insulin-dependent Diabetes Surviving an Acute Myocardial Infarction

Patients with diabetes mellitus have a high morbidity and mortality from acute myocardial infarction, the reason for which is not fully understood. The relationship between congestive heart failure symptoms, left ventricular ejection fraction, and long-term mortality was examined in 578 hospital survivors of acute myocardial infarction, 47 of whom had Type 2 (non-insulin-dependent) diabetes mellitus. None of the patients were treated with insulin. The prevalence of congestive heart failure during hospitalization was similar in patients with and without diabetes, although mean diuretic dose was higher in the former patients. Left and right ventricular ejection fraction was measured with radionuclide ventriculography in the second week after acute myocardial infarction. At discharge from the coronary care unit, patients with and without diabetes had similar left ventricular ejection fraction (with diabetes: median 46% vs without diabetes: median 43%; p = 0.89). Median right ventricular ejection fraction (62 %) was within normal limits in both groups and did not differ statistically. Survival data were obtained for all patients. The 5-year mortality was increased in patients with diabetes compared with non-diabetic patients independent of left ventricular ejection fraction. Univariate analysis showed that the cumulative 5-year mortality rate was 53 % in the group with diabetes compared with 43% in the non-diabetic group (p = 0.007). Using multivariate regression analysis presence of diabetes was found to have a significant association with long-term mortality after myocardial infarction, that was independent of age, history of hypertension, congestive heart failure symptoms during hospitalization or of either left or right ventricular ejection fractions at discharge. We conclude that the excess mortality in patients with non-insulin-dependent diabetes mellitus is not explained by available risk markers after myocardial infarction. Even though left ventricular ejection fraction and serum creatinine did not differ significantly, the apparent higher dose of Frusemide in patients with than without non-insulin-dependent diabetes mellitus might indicate that heart failure, if present, is more severe in patients with than in those without diabetes. The importance of diastolic dysfunction in this context needs to be determined.     

Effect of statins, angiotensin-converting enzyme inhibitors, and beta blockers on survival in patients >or=65 years of age with heart failure and preserved left ventricular systolic function

About half of all patients with heart failure (HF) have preserved left ventricular systolic function. Statins, angiotensin-converting enzyme inhibitors, and beta blockers have been shown to improve survival in patients with HF and low ejection fraction. However, no large national study has investigated these agents in patients with HF and preserved left ventricular ejection fraction. We evaluated a nationwide sample of 13,533 eligible Medicare beneficiaries aged >or=65 years who were hospitalized with a primary discharge diagnosis of HF and had chart documentation of preserved left ventricular ejection fraction between April 1998 and March 1999 or between July 2000 and June 2001. In Cox proportional hazard model accounting for demographic profile, clinical characteristics, treatments, physician specialty, and hospital characteristics, discharge statin therapy was associated with significant improvements in 1- and 3-year mortality (RR 0.69, 95% confidence interval [CI] 0.61 to 0.78; RR 0.73, 95% CI 0.68 to 0.79, respectively). Irrespective of total cholesterol level or coronary artery disease status, diabetes, hypertension, and age, statin therapy was associated with significant differences in mortality rates. Similarly, angiotensin-converting enzyme inhibitors were associated with better survival at 1 year (RR 0.88, 95% CI 0.82 to 0.95) and 3 years (RR 0.93, 95% CI 0.89 to 0.98). Beta-blocker therapy was associated with a nonsignificant trend at 1 year (RR 0.93, 95% CI 0.87 to 1.10) and significant survival benefits at 3 years (RR 0.92%, 95% CI 0.87 to 0.97). In conclusion, our data demonstrate that statins, angiotensin-converting enzyme inhibitors, and beta blockers are associated with better short- and long-term survival in patients >or=65 years with HF and preserved left ventricular ejection fraction.     

Comparative effects of low and high doses of the angiotensin-converting enzyme inhibitor, lisinopril, on morbidity and mortality in chronic heart failure. ATLAS Study Group

BACKGROUND: Angiotensin-converting enzyme (ACE) inhibitors are generally prescribed by physicians in doses lower than the large doses that have been shown to reduce morbidity and mortality in patients with heart failure. It is unclear, however, if low doses and high doses of ACE inhibitors have similar benefits. METHODS AND RESULTS: We randomly assigned 3164 patients with New York Heart Association class II to IV heart failure and an ejection fraction < or = 30% to double-blind treatment with either low doses (2.5 to 5.0 mg daily, n=1596) or high doses (32.5 to 35 mg daily, n=1568) of the ACE inhibitor, lisinopril, for 39 to 58 months, while background therapy for heart failure was continued. When compared with the low-dose group, patients in the high-dose group had a nonsignificant 8% lower risk of death (P=0.128) but a significant 12% lower risk of death or hospitalization for any reason (P=0.002) and 24% fewer hospitalizations for heart failure (P=0.002). Dizziness and renal insufficiency was observed more frequently in the high-dose group, but the 2 groups were similar in the number of patients requiring discontinuation of the study medication. Conclusions-These findings indicate that patients with heart failure should not generally be maintained on very low doses of an ACE inhibitor (unless these are the only doses that can be tolerated) and suggest that the difference in efficacy between intermediate and high doses of an ACE inhibitor (if any) is likely to be very small.     

Aspirin and mortality in patients treated with angiotensin-converting enzyme inhibitors: A cohort study of 11,575 patients with coronary artery disease

OBJECTIVES

The purpose of this study was to investigate the significance of the possible negative interaction between aspirin and angiotensin-converting enzyme (ACE) inhibitors.

BACKGROUND

Several provocative reports have recently suggested that aspirin is unsafe in patients with heart failure and has negative interaction with ACE inhibitors that might attenuate their beneficial effects upon survival.

METHODS

We analyzed mortality data of 11,575 patients with coronary artery disease screened for the Bezafibrate Infarction Prevention trial. A total of 1,247 patients (11%) were treated with ACE inhibitors. Of them, 618 patients (50%) used aspirin.

RESULTS

Five-year mortality was lower among patients on ACE inhibitors and aspirin than patients on ACE inhibitors without aspirin (19% vs. 27%; p < 0.001). After adjusting for confounders, treatment with aspirin and ACE inhibitors remained associated with lower mortality risk than using ACE inhibitors only (relative risk [RR] = 0.71; 95% confidence interval [CI] = 0.56 to 0.91). Subgroup analysis of 464 patients with congestive heart failure treated with ACE inhibitors revealed 221 patients (48%) on aspirin and 243 patients not on aspirin. Although clinical characteristics and therapy were similar, patients taking aspirin experienced lower mortality than patients who did not (24% vs. 34%; p = 0.001). After adjustment, treatment with aspirin was still associated with lower mortality (RR = 0.70; 95% CI = 0.49 to 0.99).

CONCLUSIONS

Among coronary artery disease patients with and without heart failure who are treated with ACE inhibitors, the use of aspirin was associated with lower mortality than treatment without aspirin. Our findings contradict the claim that aspirin attenuates the beneficial effect of ACE inhibitors and supports its use in patients with coronary artery disease treated with ACE inhibitors.     

Clinical and angiographic implications of a depressed echocardiographic ejection fraction in coronary artery disease

To evaluate the clinical and angiographic implications of a depressed echocardiographic ejection fraction (EF) in coronary artery disease, 45 patients with an echocardiographic EF < 0.50 were studied with complete cardiac catheterizations. Most of the patients had clinical evidence of a prior myocardial infarction, cardiomegaly, and/or congestive heart failure. All had coronary arteriographic evidence of multivessel disease and either reduced cardiac output, elevated left ventricular end-diastolic pressure, or both. Reduction in percentage of echocardiographic dimensional shortening closely paralleled reduction in echocardiographic EF. Forty of the 45 patients (89%) had an angiographic EF less than 0.50. There was considerable scatter of angiographic EF's with echocardiographic EF's between 0.40 and 0.50, limiting the usefulness of these latter values. However, 23 of the 24 patients (96%) with an echocardiographic EF less than 0.40 had an angiographic EF less than 0.40, and there was a linear relationship between these echocardiographic and angiographic values with a correlation coefficient (r) = 0.54 (SEE = ±0.15, p<0.05). All of the 12 patients with both reduced septal and reduced posterior wall excursion on the echocardiogram had both abnormal echocardiographic and angiographic ejection fractions, and 10 of the 12 had EF < 0.40 by both techniques. Our study suggests that coronary artery disease patients with extensive left ventricular dysfunction can be identified noninvasively, and the echocardiographic EF may be useful in deciding whether such patients may require special cardiac catheterization procedures to evaluate contractile reserve if cardiac surgery is being considered.     

Current perspectives for AT(1)-receptor blockers in the management of heart failure

Despite improvements in therapy, long-term mortality remains high in patients with heart failure and thus there remains a need for new treatment strategies to reduce the burden of mortality and morbidity associated with this condition. AT(1)-receptor blockers represent a rational approach to the management of heart failure, and have been shown to have beneficial effects on heart failure symptoms and exercise tolerance. However, the two outcome trials reported to date have not shown conclusive evidence of improvements in mortality. The potential benefits of AT(1)-receptor blockers in heart failure are currently being investigated in several trials. The CHARM programme (Candesartan in Heart failure - Assessment of Reduction in Mortality and morbidity) is the largest heart failure trial so far. This comprises three trials: CHARM Alternative, in patients with left ventricular dysfunction who are intolerant to ACE inhibitors; CHARM Added, in patients with left ventricular dysfunction who are also receiving ACE inhibitors; CHARM Preserved, in patients with preserved left ventricular systolic function (ejection fraction >40%). The primary end point will be a composite of cardiovascular mortality and hospitalisation for the treatment of heart failure. Other trials are currently investigating the effects of AT(1)-receptor blockers when used as an alternative or in addition to ACE inhibitors. The CHARM programme, together with other studies, should clarify the role of these agents in the management of heart failure.     

Comparative Effects of Losartan and Enalapril on Exercise Capacity and Clinical Status in Patients With Heart Failure

Objectives. This study was designed to determine 1) whether 12-week oral administration of losartan, an angiotensin II receptor antagonist, in patients with heart failure is well tolerated; and 2) whether functional capacity and clinical status of patients with heart failure in whom treatment with an angiotensin-converting enzyme (ACE) inhibitor is replaced with losartan for 12 weeks will remain similar to that noted in patients in whom treatment with an ACE inhibitor is continued.Background. Losartan is a specific, nonpeptide angiotensin II receptor antagonist. Although specific receptor blockade with losartan has certain theoretic advantages over nonspecific ACE inhibition, definitive demonstration of comparable effects in patients with congestive heart failure is lacking.Methods. A double-blind, multicenter, randomized, parallel, enalapril-controlled study was conducted in 116 patients with congestive heart failure (New York Heart Association functional classes II to IV) and left ventricular ejection fraction ≤45% previously treated with stable doses of ACE inhibitors and diuretic agents, with or without concurrent digitalis and other vasodilators. After a baseline exercise period, open-label ACE inhibitors were discontinued, and patients were randomly assigned to 12 weeks of therapy with losartan, 25 mg/day (n = 38); losartan, 50 mg/day (n = 40); or enalapril, 20 mg/day (n = 38). Drug efficacy was evaluated by changes in maximal treadmill exercise time (using a modified Naughton protocol), 6-min walk test, left ventricular ejection fraction and dyspnea-fatigue index. Safety was measured by the incidence of clinical and laboratory adverse experiences.Results. The treadmill exercise time and the 6-min walk test did not change significantly after replacement of ACE inhibitor therapy with losartan. Similarly, a significant change was not observed in either the dyspnea-fatigue index or left ventricular ejection fraction at the end of double-blind period relative to baseline.Conclusions. Losartan was generally well tolerated and comparable to enalapril in terms of exercise tolerance in this short-term (12-week) study of patients with heart failure. The clinical effects of long-term angiotensin II receptor blockade compared with ACE inhibition remain to be studied.