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Candesartan in heart failure--assessment of reduction in mortality and morbidity (CHARM): rationale and design.
K Swedberg1, M Pfeffer, C Granger
1Department of Medicine, Sahlgrenska University Hospital, Göteborg, Sweden.
Insights
The CHARM program investigates candesartan cilexetil for heart failure patients. This study assesses its impact on mortality and hospitalizations across diverse patient groups, including those with preserved ejection fraction.
Area of Science:
- Cardiology
- Pharmacology
- Clinical Trials
Background:
- Chronic heart failure (CHF) presents a significant healthcare challenge.
- Current treatments like ACE inhibitors improve outcomes in low ejection fraction patients, but effectiveness in preserved ejection fraction is unknown.
- A substantial portion of CHF patients (30-50%) have preserved left ventricular ejection fraction (LVEF).
Purpose of the Study:
- To evaluate the clinical utility of candesartan cilexetil, an angiotensin II type 1 receptor blocker, in a wide range of symptomatic heart failure patients.
- To assess the effects of candesartan cilexetil on cardiovascular mortality or CHF hospitalization.
- To investigate the drug's impact on other endpoints, including myocardial infarction, all-cause hospitalization, and resource utilization.
Main Methods:
- The Candesartan in Heart Failure-Assessment of Reduction in Mortality and Morbidity (CHARM) program comprises three parallel, placebo-controlled studies.
- Enrolled patients include those with LVEF ≤ 40% (ACE-inhibitor treated or intolerant) and LVEF > 40% (not treated with ACE inhibitors).
- A total of 6,500 patients were randomized across 26 countries, with a minimum follow-up of 2 years.
Main Results:
- The CHARM program's results are pending completion of patient enrollment and follow-up.
- The primary endpoint is the composite of cardiovascular death or CHF hospitalization.
- Secondary endpoints include myocardial infarction, all-cause hospitalization, and healthcare resource utilization.
Conclusions:
- The CHARM program aims to provide crucial data on candesartan cilexetil's efficacy in a broad spectrum of heart failure patients.
- Findings will inform treatment strategies for both reduced and preserved ejection fraction heart failure.
- The study is expected to significantly impact the management of symptomatic heart failure.
Background:
Chronic heart failure (CHF) is an increasing burden to health care. Pharmacological treatment with angiotensin-converting enzyme (ACE) inhibitors and beta blockers improve survival and reduce hospitalizations in patients with low left ventricular ejection fraction (LVEF). Despite these therapies, morbidity and mortality remains problematic. Furthermore, 30% to 50% of patients with CHF have a preserved LVEF. It is not known if treatments are of benefit in this group.
Design:
Candesartan in Heart Failure-Assessment of Reduction in Mortality and Morbidity (CHARM) is a program designed to investigate the clinical usefulness of the long-acting angiotensin II type 1 receptor blocker, candesartan cilexetil, in a broad spectrum of patients with symptomatic heart failure. Patients with systolic dysfunction, tolerant or intolerant to an ACE-inhibitor, and patients with preserved systolic function are included. Specifically, the CHARM program consists of 3 independent, parallel, placebo-controlled studies in patients with (1) LVEF less than or equal to 40%, ACE-inhibitor treated (n = 2,300); (2) LVEF less than or equal to 40%, ACE-inhibitor intolerant (n = 1,700); (3) LVEF greater than 40%, not treated with ACE inhibitors (n = 2,500). The 3 studies will be combined to evaluate the effect of candesartan cilexetil on all-cause mortality in the broad spectrum of symptomatic heart failure. The primary objective in each trial is to evaluate the effects on the combined endpoint of cardiovascular mortality or CHF hospitalization. Other endpoints include the effects on myocardial infarction, all-cause hospitalization, and resource utilization. CHARM is intended to randomize 6,500 patients with symptomatic heart failure from 26 countries in Europe, the United States, Canada, South Africa, and Australia. The CHARM program started to enroll patients in March 1999. The follow-up period is a minimum of 2 years. The study is expected to end in the third quarter of 2002.