Angiotensin inhibition in heart failure

Area of Science:

• Cardiology
• Pharmacology

Background:

• Heart failure survival rates are poor, comparable to or worse than many cancers.
• The renin-angiotensin-aldosterone system (RAAS) plays a key role in heart failure pathophysiology.
• Angiotensin-converting enzyme (ACE) inhibitors incompletely block RAAS and affect bradykinin levels.

Purpose of the Study:

• To evaluate the efficacy and safety of the angiotensin receptor blocker (ARB) candesartan in patients with symptomatic heart failure.
• To assess candesartan's benefits in patients intolerant to ACE inhibitors, those already on ACE inhibitors, and those with preserved left ventricular ejection fraction (LVEF).

Main Methods:

• The Candesartan in Heart failure Assessment of Reduction in Mortality and morbidity (CHARM) programme enrolled three distinct heart failure populations.
• Candesartan (32 mg daily) was compared to placebo in CHARM-Alternative (ACE-I intolerant), CHARM-Added (on ACE-I), and CHARM-Preserved (preserved LVEF).
• Primary composite endpoint: cardiovascular death or heart failure hospitalization.

Main Results:

• CHARM-Alternative and CHARM-Added showed significant reductions in the primary composite endpoint.
• CHARM-Preserved demonstrated a significant reduction in heart failure hospitalizations, though the primary endpoint did not reach statistical significance.
• Overall, candesartan showed a borderline reduction in all-cause mortality and a clear reduction in cardiovascular mortality, with a 12% reduction in all-cause mortality in low LVEF patients.

Conclusions:

• Candesartan provides clinical benefits in heart failure, both independently and additively with ACE inhibitors.
• Benefits were observed regardless of beta-blocker use.
• Candesartan improved outcomes in patients with preserved LVEF, particularly regarding heart failure hospitalizations, necessitating careful monitoring of blood pressure and renal function.