An analysis from the CHARM-Added trial provided evidence that the clinical benefits of Candesartan ( Atacand / Ratacand ) in reducing the risk of cardiovascular death and heart failure hospitalizations in patients with symptomatic heart failure and reduced heart pump function were not modified by baseline dose of ACE inhibitor, beta-blocker use at baseline, or ACE inhibitor dose during the trial.
The analysis also supports the concept that ACE inhibitors and Candesartan, an ARB ( angiotensin receptor blocker ), in addition to sharing some common clinical effects, can also complement each other when used together to further improve these outcomes in patients with heart failure.

In the CHARM-Added trial ( n=2548 ), Candesartan reduced the relative risk for the primary end point of cardiovascular death or heart failure hospitalization significantly compared to placebo ( hazard ratio ( HR ) 0.85; p=0.011 ). This outcome was consistent in patients taking a guideline-recommended ACE inhibitor dose ( n=1291 ) and for those taking an FDA-designated maximum ACE inhibitor dose ( n=529 ) ( hazard ratio ( HR ) 0.79; HR 0.75, respectively ).

The results of this analysis demonstrated that the addition of Candesartan to other standard therapies including ACE inhibitors, even at maximum doses, and in combination with beta-blockers, can further reduce serious consequences of heart failure, specifically heart disease related death and heart failure hospitalizations. Monitoring of blood pressure, serum creatinine, and serum potassium is recommended during dose escalation of Candesartan and periodically thereafter in order to minimize potential side effects.

The CHARM program, sponsored by AstraZeneca, consisted of three parallel, randomized, placebo-controlled, double-blind trials in 7,599 symptomatic heart failure patients. CHARM-Added ( 2,548 patients receiving an ACE inhibitor ) and CHARM-Alternative ( 2,028 patients not receiving an ACE inhibitor due to intolerance ) enrolled patients with left-ventricular ejection fraction ( LVEF ) less than or equal to 40%, and CHARM-Preserved ( n=3023 ) enrolled patients with LVEF > 40%.
Patients were randomized to either Candesartan or matching placebo initiated at 4 mg or 8 mg once daily and titrated as tolerated to 32 mg once daily added to conventional therapy. Patients were followed for a minimum of two years, with median follow-up of 38 months.
The primary end point of each trial was cardiovascular death or heart failure hospitalization.

The recommended initial dose for treating heart failure is 4 mg once daily. The target dose is 32 mg once daily, which is achieved by doubling the dose at approximately 2-week intervals, as tolerated by the patient.

In heart failure patients receiving Candesartan, hypotension, increases in serum creatinine, and hyperkalemia have occurred. Caution should be observed for hypotension when initiating therapy. Evaluation of patients with heart failure should always include assessment of renal function and volume status.

Source: American Heart Journal, 2006


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