CHARM-Preserved: Candesartan in Heart failure: Assessment of Reduction in Mortality and morbidity - Preserved Purpose To determine whether the angiotensin.

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CHARM-Preserved: Candesartan in Heart failure: Assessment of Reduction in Mortality and morbidity - Preserved Purpose To determine whether the angiotensin II receptor blocker candesartan is beneficial in patients with chronic heart failure (CHF) and preserved left ventricular systolic function Reference Yusuf S, Pfeffer MA, Swedberg K, et al. for the CHARM Investigators and Committees. Effects of candesartan in patients with chronic heart failure and preserved left-ventricular ejection fraction: the CHARM-Preserved trial. Lancet 2003;362:777–81.

CHARM-Preserved: Candesartan in Heart failure: Assessment of Reduction in Mortality and morbidity - Preserved - TRIAL DESIGN - Design Multicenter, multinational, randomized, double-blind, placebo-controlled Patients 3023 patients aged >18 years with symptomatic CHF (NYHA class II–IV), who had left ventricular ejection fraction >40% Follow up and primary endpoint Primary endpoint: cardiovascular death or hospital admission for CHF. Median 36.6 months follow up. Treatment Placebo or candesartan titrated to 32 mg once daily

CHARM-Preserved: Candesartan in Heart failure: Assessment of Reduction in Mortality and morbidity - Preserved - TRIAL DESIGN continued- Baseline characteristics (%) 67.1 136.3 77.8 59 60 39 1 36 34 31 Placebo (n=1509) 67.2 136.0 77.8 61 62 37 2 35 36 29 Candesartan (n=1514) 44 28 64 Placebo (n=1509) 19 56 12 59 43 57 9 23 45 29 65 20 56 11 58 41 9 22 Candesartan (n=1514) Age (years)a History MI Male Diabetes mellitus NYHA class: Hypertension II Heart failure cause III Ischemic IV Idiopathic LVEF Hypertensive 41–49% Medications 50–59% ACE inhibitor >60% Beta-blocker BP (mmHg)a Spironolactone Systolic Aspirin Diastolic Lipid-lowering drug aMean Yusuf et al. Lancet 2003;362:777–81.

CHARM-Preserved: Candesartan in Heart failure: Assessment of Reduction in Mortality and morbidity - Preserved - RESULTS - Nonsignificant trend to reduction in primary outcome of cardiovascular death or hospital admission for CHF in candesartan group compared with placebo (22 vs. 24.3%, P=0.118) Secondary outcomes – composites of primary outcome and MI, nonfatal stroke and coronary revascularization – also showed nonsignificant trend Total number of hospital admissions for CHF significantly reduced in candesartan group (402 vs. 566, P=0.014) All-cause mortality similar in both groups (244 vs. 237 patients) Permanent discontinuation due to adverse event or laboratory abnormality more frequent with candesartan (17.8 vs. 13.5%, P=0.001)

CHARM-Preserved: Candesartan in Heart failure: Assessment of Reduction in Mortality and morbidity - Preserved - RESULTS continued - Cardiovascular death or hospital admission for CHF Proportion 50 with event Placebo Candesartan (%) 40 30 Hazard ratio 0.89 (95% CI 0.77–1.03) P = 0.118 20 10 1.0 2.0 3.0 3.5 Years after randomization Yusuf et al. Lancet 2003;362:777–81.

CHARM-Preserved: Candesartan in Heart failure: Assessment of Reduction in Mortality and morbidity - Preserved - RESULTS continued - Primary and secondary outcomes Placebo Candesartan (n=1509) (n=1514) Hazard ratio P (95% CI) No. (%) No. (%) Cardiovascular death or 366 (24.3) 333 (22.0) 0.89 (0.77–1.03) 0.118 hospital admission for CHF Cardiovascular death 0.99 (0.80–1.22) 0.918 170 (11.2) (11.3) Hospital admission for CHF 0.85 (0.72–1.01) 0.072 241 (15.9) 276 (18.3) Cardiovascular death, hospital admission for CHF, or MI 0.90 (0.78–1.03) 0.126 365 (24.1) 399 (26.4) Cardiovascular death, hospital admission for CHF, MI, or stroke 0.88 (0.77–1.01) 0.078 388 (25.6) 429 (28.4) Cardiovascular death, hospital admission for CHF, MI, stroke, or coronary revascularization 0.91 (0.80–1.03) 0.123 460 (30.4) 497 (32.9) Yusuf et al. Lancet 2003;362:777–81.

CHARM-Preserved: Candesartan in Heart failure: Assessment of Reduction in Mortality and morbidity - Preserved - RESULTS continued - Discontinuation because of adverse events Placebo Candesartan Cause of discontinuation (n=1509) (n=1514) P No. (%) No. (%) Hypotension 0.009 37 (2.4) 17 (1.1) Increase in creatinine 0.0005 72 (4.8) 36 (2.4) Hyperkalemia 0.029 22 (1.5) 9 (0.6) Any adverse event or laboratory abnormality 0.001 270 (17.8) 204 (13.5) Yusuf et al. Lancet 2003;362:777–81.

CHARM-Preserved: Candesartan in Heart failure: Assessment of Reduction in Mortality and morbidity - Preserved - SUMMARY - In patients who had symptomatic CHF and preserved left ventricular systolic function, with candesartan there was no significant reduction of the following, although the trend was favorable: Cardiovascular death or hospitalization for CHF Secondary outcomes that combined these with MI, stroke and coronary revascularization procedures However, the total number of hospital admissions for CHF was significantly reduced in the candesartan group.