Renin–Angiotensin System Inhibition, Worsening Renal Function, and Outcome in Heart Failure Patients With Reduced and Preserved Ejection Fraction

In the past 3 decades, the introduction of renin–angiotensin aldosterone system (RAAS) inhibitors has significantly improved morbidity and mortality in chronic heart failure (HF) patients with reduced ejection fraction (HFREF). Although RAAS inhibitors have beneficial effects on the heart and vasculature, they also induce a small decrease in renal function as estimated by glomerular filtration rate (eGFR). This effect is caused by the effect of RAAS inhibitors on renal autoregulation, primarily preventing efferent (post) glomerular arteriolar vasoconstriction. This action is often considered to be harmful because data from large epidemiological studies and meta-analyses suggest that even a slight decrease in eGFR is associated with an increased risk of poor clinical outcomes. However, this assumption based on associations is too simplistic. In fact, a recent meta-analysis showed that even if worsening renal function (WRF) occurs during the initiation of RAAS inhibition in patients with HFREF, the mortality benefit is maintained, although the net benefit of RAAS blockade may be less in patients with WRF because the favorable effects of RAAS blockade are partially offset by the risk associated with WRF. However, it is clear that the cause of WRF, rather than its occurrence per se, is what seems to be most important, and WRF caused by RAAS blockade has been dubbed “pseudo-WRF”.