The role of ARBS in the management of CHF

Chronic heart failure (CHF) is a highly disabling disease with a high prevalence in the general population. Current treatment with drugs such as beta-blockers, diuretics, digitalis and angiotensin-converting enzyme (ACE) inhibitors has dramatically improved the mortality and morbidity of patients, and has afforded a better quality of life. However, angiotensin-converting enzymes are not tolerated by or cannot be used in all patients.

Data from previous trials had demonstrated a certain benefit of using angiotensin receptor blockers (ARB) in patients with CHF. However, important questions remained unanswered on the possibility of combining ARBs with ACE inhibitors and on the use of ARBs in patients who cannot tolerate ACE inhibitors.

The CHARM program comprised three individual clinical trials designed to explore the safety and efficacy of the ARB candesartan in the treatment of chronic heart failure in

i) patients with reduced systolic function who cannot tolerate ACE inhibitors,

ii) patients with reduced systolic function who are already on treatment with ACE inhibitors, and

iii) patients with preserved systolic function with or without concomitant therapy with ACE inhibitors.

The results of the overall CHARM program demonstrated a clear benefit of candesartan in the management of heart failure, independent of systolic function or concomitant treatment with ACE inhibitors or other drugs, such that adding candesartan to the best available therapy significantly reduced heart failure-related mortality and morbidity in patients with CHF.

After the official publication of the results of the CHARM program in The Lancet in September, an open debate was held on October 17 in Barcelona, Spain by some of the main investigators of the CHARM study to discuss the implications of the results compared with those of other studies of ARBs in CHF. The objective was to characterise the efficacy of individual ARBs in the treatment of CHF.

CHARM is the only study that has demonstrated the efficacy and usefulness of a particular ARB, candesartan, as a first-line therapy for CHF, regardless of systolic function and co-treatments. The benefits of treatment with candesartan were achieved on top of other effective concomitant therapies, including ACE inhibitors and beta-blockers, emphasising the positive role of candesartan in the drug armamentarium for heart failure.

The CHARM study was sponsored and conducted by AstraZeneca. Candesartan was discovered and originally synthesized by Takeda Chemical Industries, Ltd, and it was jointly developed with AstraZeneca.