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Relationship of background ACEI dose to benefits of candesartan in the CHARM-Added trial

Relationship of background ACEI dose to benefits of candesartan in the CHARM-Added trial. CHARM-Added: Study design. C andesartan in H eart failure: A ssessment of R eduction in M ortality and morbidity (CHARM)-Added. Randomized, double-blind

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Relationship of background ACEI dose to benefits of candesartan in the CHARM-Added trial

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  1. Relationship of background ACEI dose to benefits of candesartan in the CHARM-Added trial

  2. CHARM-Added: Study design Candesartan in Heart failure: Assessment of Reduction in Mortality and morbidity (CHARM)-Added Randomized, double-blind NYHA class II–IV, LVEF ≤40%, stable ACEI dose for ≥30 days N = 2548 Candesartan 32 mg qd n = 1276 Placebo n = 1272 Median follow-up: 41 months Primary outcome: CV death or hospitalization for HF ACEI = angiotensin-converting enzyme inhibitor McMurray JJV et al. Lancet. 2003;362:761-71.

  3. CHARM-Added: Baseline characteristics by ACEI dose McMurray JJV et al. Am Heart J. 2006;151:985-91.

  4. CHARM-Added: Daily ACEI dose Subgroup analysis, most commonly used ACEIs All patients(N = 2548) ≥Recommended(CHARM prespecified)*(n = 1291) ≥Maximum (FDA)(n = 529) *Based on European Society of Cardiology guidelines †Not indicated for heart failure McMurray JJV et al. Am Heart J. 2006;151:985-91.

  5. CHARM-Added: Primary outcome of CV death or HF hospitalization N = 2548 Patients (n) Candesartan better Placebo better P value for interaction 0.26 0.29 Recommended dose of ACEI CHARM prespecified Maximum dose of ACEI FDA 2005 CHARM-Added CHARM-Alternative Pooled results (low LVEF patients) No Yes No Yes 1257 1291 2019 529 2548 2028 4576 0.6 0.8 1 1.2 Hazard ratio (95% Cl) McMurray JJV et al. Am Heart J. 2006;151:985-91.

  6. CHARM-Added: Primary outcome in patients taking a -blocker n = 1413 Patients (n) Candesartan better Placebo better P value for interaction 0.69 0.64 CV death or HF hospitalization Recommended dose of ACEI CHARM prespecified Maximum dose of ACEI FDA 2005 All patients No Yes No Yes 692 721 1100 313 1413 0.6 0.8 1 1.2 Hazard ratio (95% Cl) McMurray JJV et al. Am Heart J. 2006;151:985-91.

  7. Summary: CHARM-Added • Candesartan reduced CV death or HF hospitalization in patients taking no ACEI, a moderate ACEI dose, or a high ACEI dose • Benefits of candesartan in HF patients were not modified by either ACEI dose or concomitant therapy with a -blocker • ACEIs and angiotensin receptor blockers (ARBs) have distinct and complementary mechanisms of action • Combined use of an ACEI and the ARB, candesartan, improved outcomes in patients with HF vs ACE inhibition alone McMurray JJV et al. Am Heart J. 2006;151:985-91.

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