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BACKGROUND: Losartan (Cozaar, Hyzaar), a specific angiotensin-II receptor antagonist (ACE-II), is associated with hemodynamic, symptomatic, and neurohormonal improvement in heart failure. In the Evaluation of Losartan in the Elderly (ELITE) study, an unexpected reduction in mortality was observed in patients randomized to losartan compared with captopril. This meta-analysis is an attempt to put this result into perspective with other studies.
POPULATION STUDIED: Most of the patients studied were white men, with a mean age of approximately 60 years. Most had ischemic heart disease and had been given a diagnosis of heart failure within the last 5 years. Their mean left ventricular ejection fractions ranged from 23% to 31% in the studies.
STUDY DESIGN AND VALIDITY: This was a meta-analysis of 8 studies in the Losartan Heart Failure Program. Two of those studies did not meet the criteria for inclusion (one was a pharmacokinetic study; the other was a single-dose study). This left 6 multicenter randomized double-blinded controlled trials for analysis. A total of 1894 patients were enrolled in these 6 studies, of whom 1154 were randomized to receive losartan and 740 to a control (274 to placebo, 96 to enalapril, 370 to captopril). There were no significant differences between groups regarding any demographic or clinical characteristics. Concurrent use of an ACE inhibitor was not permitted.
OUTCOMES MEASURED: The primary outcome was all-cause mortality.
RESULTS: There was a total of 47 deaths (6.35%) in the control groups compared with 36 (3.12%) in the losartan groups during double-blinded therapy (mean follow-up time=25.4 weeks, P=.004). The combined odds ratio of observed mortality was 0.50 (95% confidence interval [CI], 0.32-0.81), indicating a 50% relative reduction in the risk of death for patients with heart failure taking losartan (absolute risk reduction=3.23%, number needed to treat=31). A number of subgroups of studies did not reach significance; that is, the group that switched from ACE to ACE-II (odds ratio [OR]=1.07; 95% CI, 0.23-4.89), the ACE inhibitor controlled studies (OR=0.6; 95% CI, 0.34-1.04), and the group in which patients had previously received an ACE inhibitor (OR=0.76; 95% CI, 0.3-1.96).
Losartan appears to reduce mortality in patients with moderate to severe heart failure (ejection fraction=20%-30%). There is insufficient evidence to conclude that this is a class effect (ie, all ACE-IIs) or that there is an increased benefit over ACE inhibitors.
BACKGROUND: Losartan (Cozaar, Hyzaar), a specific angiotensin-II receptor antagonist (ACE-II), is associated with hemodynamic, symptomatic, and neurohormonal improvement in heart failure. In the Evaluation of Losartan in the Elderly (ELITE) study, an unexpected reduction in mortality was observed in patients randomized to losartan compared with captopril. This meta-analysis is an attempt to put this result into perspective with other studies.
POPULATION STUDIED: Most of the patients studied were white men, with a mean age of approximately 60 years. Most had ischemic heart disease and had been given a diagnosis of heart failure within the last 5 years. Their mean left ventricular ejection fractions ranged from 23% to 31% in the studies.
STUDY DESIGN AND VALIDITY: This was a meta-analysis of 8 studies in the Losartan Heart Failure Program. Two of those studies did not meet the criteria for inclusion (one was a pharmacokinetic study; the other was a single-dose study). This left 6 multicenter randomized double-blinded controlled trials for analysis. A total of 1894 patients were enrolled in these 6 studies, of whom 1154 were randomized to receive losartan and 740 to a control (274 to placebo, 96 to enalapril, 370 to captopril). There were no significant differences between groups regarding any demographic or clinical characteristics. Concurrent use of an ACE inhibitor was not permitted.
OUTCOMES MEASURED: The primary outcome was all-cause mortality.
RESULTS: There was a total of 47 deaths (6.35%) in the control groups compared with 36 (3.12%) in the losartan groups during double-blinded therapy (mean follow-up time=25.4 weeks, P=.004). The combined odds ratio of observed mortality was 0.50 (95% confidence interval [CI], 0.32-0.81), indicating a 50% relative reduction in the risk of death for patients with heart failure taking losartan (absolute risk reduction=3.23%, number needed to treat=31). A number of subgroups of studies did not reach significance; that is, the group that switched from ACE to ACE-II (odds ratio [OR]=1.07; 95% CI, 0.23-4.89), the ACE inhibitor controlled studies (OR=0.6; 95% CI, 0.34-1.04), and the group in which patients had previously received an ACE inhibitor (OR=0.76; 95% CI, 0.3-1.96).
Losartan appears to reduce mortality in patients with moderate to severe heart failure (ejection fraction=20%-30%). There is insufficient evidence to conclude that this is a class effect (ie, all ACE-IIs) or that there is an increased benefit over ACE inhibitors.
BACKGROUND: Losartan (Cozaar, Hyzaar), a specific angiotensin-II receptor antagonist (ACE-II), is associated with hemodynamic, symptomatic, and neurohormonal improvement in heart failure. In the Evaluation of Losartan in the Elderly (ELITE) study, an unexpected reduction in mortality was observed in patients randomized to losartan compared with captopril. This meta-analysis is an attempt to put this result into perspective with other studies.
POPULATION STUDIED: Most of the patients studied were white men, with a mean age of approximately 60 years. Most had ischemic heart disease and had been given a diagnosis of heart failure within the last 5 years. Their mean left ventricular ejection fractions ranged from 23% to 31% in the studies.
STUDY DESIGN AND VALIDITY: This was a meta-analysis of 8 studies in the Losartan Heart Failure Program. Two of those studies did not meet the criteria for inclusion (one was a pharmacokinetic study; the other was a single-dose study). This left 6 multicenter randomized double-blinded controlled trials for analysis. A total of 1894 patients were enrolled in these 6 studies, of whom 1154 were randomized to receive losartan and 740 to a control (274 to placebo, 96 to enalapril, 370 to captopril). There were no significant differences between groups regarding any demographic or clinical characteristics. Concurrent use of an ACE inhibitor was not permitted.
OUTCOMES MEASURED: The primary outcome was all-cause mortality.
RESULTS: There was a total of 47 deaths (6.35%) in the control groups compared with 36 (3.12%) in the losartan groups during double-blinded therapy (mean follow-up time=25.4 weeks, P=.004). The combined odds ratio of observed mortality was 0.50 (95% confidence interval [CI], 0.32-0.81), indicating a 50% relative reduction in the risk of death for patients with heart failure taking losartan (absolute risk reduction=3.23%, number needed to treat=31). A number of subgroups of studies did not reach significance; that is, the group that switched from ACE to ACE-II (odds ratio [OR]=1.07; 95% CI, 0.23-4.89), the ACE inhibitor controlled studies (OR=0.6; 95% CI, 0.34-1.04), and the group in which patients had previously received an ACE inhibitor (OR=0.76; 95% CI, 0.3-1.96).
Losartan appears to reduce mortality in patients with moderate to severe heart failure (ejection fraction=20%-30%). There is insufficient evidence to conclude that this is a class effect (ie, all ACE-IIs) or that there is an increased benefit over ACE inhibitors.