Worsening renal function and outcome in heart failure patients with reduced and preserved ejection fraction and the impact of angiotensin receptor blocker treatment: data from the CHARM ‐study programme

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 m 2 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 .