Key result
Worsening renal function after candesartan or placebo is linked to ~26% more CV deaths or HF hospitalizations.
Why the study?
Does candesartan compared with placebo affect the incidence of worsening renal function and subsequent clinical outcomes in patients with heart failure?
RCT (n=2,405)
randomized
Does candesartan compared with placebo affect the incidence of worsening renal function and subsequent clinical outcomes in patients with heart failure?
Effect estimate: HR 1.26 (95% CI 1.03-1.54)
p-value: p=0.022
Worsening renal function during initiation of renin-angiotensin-aldosterone system inhibition is more common with candesartan than placebo and is associated with worse clinical outcomes in both HFrEF and HFpEF.
Worsening renal function signals higher event risk in HF; leaves open whether it modifies candesartan benefit.
Aims We investigated the association between worsening renal function (WRF) that occurs during renin–angiotensin–aldosterone system inhibition initation and outcome in heart failure (HF) patients with preserved ejection fraction (HFPEF) and compared this with HF patients with reduced ejection fraction (HFREF). Methods and results We examined changes in estimated glomerular filtration rate (GFR) and the relationship between WRF (defined as ≥26.5 µmol/L and ≥25% increase in serum creatinine from baseline to 6 weeks) and outcome, according to randomized treatment, in patients with HFREF (EF <45%; n = 1569) and HFPEF (EF ≥45%; n = 836) in the CHARM programme. The primary outcome was cardiovascular death or HF hospitalization. Estimated GFR decreased 9.0 ± 21 vs. 4.0 ± 21 mL/min/1.73 m2 with candesartan and placebo, respectively, and this was similar in HFREF and HFPEF. WRF developed more frequently with candesartan, 16% vs. 7%, P < 0.001, with similar findings in patients with HFREF and HFPEF. WRF was associated with a higher risk of the primary outcome: multivariable hazard ratio (HR) 1.26, 95% confidence interval 1.03–1.54, P = 0.022, in both treatment groups, and in both HFREF and HFPEF (P for interaction 0.98). In HFREF, WRF was mostly related to HF hospitalization, while in HFPEF, WRF seemed more associated with mortality. Conclusions GFR decreased more and WRF was more common with candesartan compared with placebo, and this was similar in HFREF and HFPEF. WRF was associated with worse outcomes in HFREF and HFPEF. Although no formal interaction was present, the association between candesartan treatment, WRF, and type of clinical outcome was slightly different between HFREF and HFPEF.
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Damman et al. (2016) conducted an RCT in Heart failure with reduced and preserved ejection fraction (n=2,405). Candesartan vs. Placebo was evaluated on Cardiovascular death or HF hospitalization (HR 1.26, 95% CI 1.03-1.54, p=0.022). Worsening renal function after initiating candesartan or placebo was associated with increased risk of cardiovascular death or heart failure hospitalization (HR 1.26; 95% CI 1.03-1.54; P=0.022).
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