Worsening renal function during renin-angiotensin-aldosterone system inhibitor initiation and long-term outcomes in patients with left ventricular systolic dysfunction

Impaired renal function is associated with worse clinical outcomes in patients with LV systolic dysfunction (LVSD) and heart failure. Renin?angiotensin?aldosterone system (RAAS) inhibitors provide clinical benefit in these settings and often worsen renal function. It is not clear whether worsening renal function (WRF) in patients exposed to these agents predicts a worse prognosis or merely reflects the pharmacological action of the drug on the kidney. Methods and results We performed a meta-analysis of all RAAS inhibitor LVSD trials reporting on outcomes according to WRF (as per individual study definition) in both active intervention and placebo groups. Five major studies (SOLVD, SAVE, RALES, Val-HeFT and EPHESUS) contributed, with 20?573 patients. Compared with placebo, RAAS inhibitors reduced all-cause mortality overall [n?=?20?573, relative risk ratio (RR) 0.91, 95 confidence interval (CI) 0.86?0.95, P?=?0.0003], in the group with no WRF (n?=?18?209, RR 0.91, 95 CI 0.83?0.99, P?=?0.04), and in the WRF group (n?=?2364, RR 0.72, 95 CI 0.62?0.84, P?