# Presentation: 723931

## Candesartan in HFBenefit/Risk

**James B. Young, MD**
**Cleveland Clinic Foundation**

## CHARM Program of Clinical Trials

**Studied a broad patient population**
**Comprehensively characterized the risks associated with the treatment, particularly the combination of ACE inhibitor and candesartan**
**Clearly delineated net benefits for the chronic heart failure (CHF) patient with LV systolic dysfunction treated with candesartan and combination ACE inhibitor/candesartan**

## CHARM Added

**Addressed the previously unresolved question whether adding the ARB candesartan to ACE inhibitor therapy in CHF patients with LV systolic dysfunction:**
**Provides incremental benefit by reducing the risk of CV death or CHF hospitalization**
**Provides benefit in patients receiving evidence-based doses of ACE inhibitors proven effective in previous HF trials**
**Has a favorable benefit to risk profile**

## Benefit to Risk Profile For Candesartan CHARM Added

**15% relative risk reduction (*****p***** = 0.011) for the primary endpoint, ****CV death or CHF hospitalization with a 41-month median follow-up**
**Per 1000 patient-years **
**Absolute risk reduction of 25 patients having a primary endpoint**
**No increased risk for all-cause mortality or all-cause hospitalization**

|  | Events, per 1000 follow-up yr |  |  |
| --- | --- | --- | --- |
|  | Placebo | Candesartan | Events prevented |
| CV death or CHF hospitalization | 166.3 | 141.2 | 25.1 |
| 	CV mortality | 93.3 | 78.5 | 14.8 |
| 	First CHF hospitalization | 110.1 | 90.3 | 19.8 |
| All-cause hospitalization | 391.1 | 371.1 | 20.0 |
| All-cause mortality | 110.7 | 98.0 | 12.7 |
| All-cause mortality orall-cause hospitalization  | 431.4 | 411.1 | 20.3 |

## CHF With LV Systolic DysfunctionCHARM Added

**Candesartan, at a target dose of 32 mg once daily, significantly reduces the risk for ****CV death or CHF hospitalization**
**Net benefit was demonstrated when candesartan was added to an ACE inhibitor**
**Net benefit was demonstrated independent of ACE inhibitor dose or choice of ACE inhibitor**

## Recommended Monitoring

**Hypotension, hyperkalemia, and abnormal renal function are expected events in this population**
**Proposed instructions for use are consistent with those provided to the CHARM investigators and with good clinical management of CHF patients**
**Emphasizes attention to volume status, BP, serum creatinine, and serum potassium prior to treatment**
**Recommended monitoring of these measures with initiation of candesartan, with dose titration, and periodically thereafter**

## Conclusions

**Addition of candesartan to the ACE inhibitor treatment ****of CHF patients results in a substantial cardiovascular morbidity/mortality benefit**
**The adverse event profile of candesartan in heart failure patients is consistent with the pharmacology of the drug and the health status of the patients**
**A positive benefit-risk profile is further supported by numerical reductions in both all-cause hospitalization and all-cause mortality**
**These findings support the use of candesartan with or without an ACE inhibitor**** ****for the routine management of heart failure in patients with LV systolic dysfunction**