Is CHARM-added candesartan tolerated in 'real-life” patients with advanced chronic heart failure?

Introduction: The CHARM-added trial demonstrated that the addition of candesartan to therapy with ACE-inhibitors and beta-blockers (BB) resulted in a significant reduction in cardiovascular deaths and hospital admissions for chronic heart failure (CHF) patients with a low ejection fraction (EF). There is concern that in “real life” practice, there may be an increase in adverse events. We examined the tolerability of candesartan in addition to ACE-inhibitors and BBs in an advanced heart failure population. Methods: We retrospectively examined consecutive case notes of patients currently attending the Scottish National Advanced Heart Failure Service. Results: 107 patients (mean age 53) were included. Mean EF was 17.6. Mean creatinine was 120. 22% were on spironolactone. 12 patients were ACE-inhibitor intolerant. 57 were not established on optimal doses of beta blockers or ACE inhibitors and were not yet challenged with candesartan. 38 patients were initiated on candesartan in addition to maximum tolerated doses of ACE-inhibitors and BBs. Of these 13 (34%) had reached a maximum tolerated dose of candesartan; 13 (34%) were undergoing candesartan titration; 12 (32%) were intolerant of candesartan. Of the 13 on a maximum tolerated dose, the mean dose achieved was 24mg. 8 patients were established on the top dose of 32mg. Of the remaining 5 patients, titration was limited by the following: 2 had symptomatic hypotension; 1 had worsening renal function; 1 developed hyperkalaemia; 1 felt non-specifically unwell. Of the 12 patients intolerant of candesartan, the reasons for discontinuation were: 7 developed symptomatic hypotension, 2 developed hyperkalaemia; 2 felt non-specifically unwell; 1 had asymptomatic severe hypotension. No patient was discontinued for worsening renal function. Those on a maximal tolerated dose of candesartan had a mean reduction in BP of 8/5, whereas those who were intolerant of candesartan had a mean reduction in BP of 13/14. Conclusion: In a population of young patients with advanced heart failure, a third were titrated to maximum tolerated doses of candesartan over and above established therapies and a third were undergoing titration. One third were intolerant primarily due to symptomatic postural hypotension. The addition of candesartan to established therapy in this population is achievable and safe with appropriate monitoring