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 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.