Effects of dual blockade in heart failure and renal dysfunction: Systematic review and meta-analysis

Abstract

Objective: The effect of dual renin–angiotensin system (RAS) inhibition in heart failure (HF) is still controversial. Systematic reviews have shown that dual RAS blockade may reduce mortality and hospitalizations, yet it has been associated with the increased risk of renal dysfunction (RD). Surprisingly, although RD in patients with HF is frequent, the effect of combining RAS inhibitors in HF patients with RD has never been studied in a meta-analysis. Methods: A systematic review and meta-analysis of randomized clinical trials involving HF patients with RD who received dual blockade analyzing death, cardiovascular (CV) death or HF hospitalization, and adverse events. Results: Out of 2258 screened articles, 12 studies were included (34,131 patients). Compared with monotherapy, dual RAS inhibition reduced hazard ratio of death to 0.94 ( p=0.07) and significantly reduced CV death or HF hospitalization to 0.89 ( p=0.0006) in all individuals, and to 0.86 ( p=0.005) in patients with RD and to 0.91 ( p=0.04) without RD. Nevertheless, dual RAS blockade significantly increased the risk of renal impairment (40%), hyperkalemia (44%), and hypotension (42%), although discontinuation of treatment occurs only in 3.68% versus 2.19% ( p=0.00001). Conclusions: Dual RAS inhibition therapy reduces the risk of CV death or HF hospitalization. However, cautions monitoring for specific adverse events may be warranted.

2023 ESH Guidelines for the management of arterial hypertension The Task Force for the management of arterial hypertension of the European Society of Hypertension

“…ACEis, ARBs or aliskiren should not be combined because no added benefit on CV outcomes has been shown by dual RAS inhibition [559]. Although double RAS blockade has been shown to have a greater antialbuminuric effect and might have favorable effects in HF, the association may cause an excess of adverse events, with an increased risk of kidney function impairment (40%), hyperkalemia (44%) and hypotension (42%) [560] in patients with a high CV risk [559] or type 2 diabetes [561]. Co-medications susceptible to significant drug interactions mediated by P-gp or CYP3A4 for eplerenone…”

Dual Blockade of the Renin-Angiotensin System: A Strategy that Should Be Reconsidered in Cardiorenal Diseases?

“…These results suggest that dual RAS blockade reduced the risk of cardiovascular death and hospitalization for heart failure but did not increase the risk of renal damage. However, specific adverse events must be monitored during treatment [41]. In a RCT, Saglimbene et al [42] reported that patients may tolerate ARBs better than ACEIs.…”