Key result
Dual RAS inhibition cuts major events ~14% vs monotherapy in HF patients with renal dysfunction.
Why the study?
The effect of dual RAS inhibition in heart failure remains controversial due to increased risk of renal dysfunction, and its effect in heart failure patients with renal dysfunction had never been evaluated in a meta-analysis.
Does dual RAS inhibition reduce mortality and cardiovascular events in heart failure patients with renal dysfunction compared to monotherapy?
Meta-Analysis (n=34,131)
Does dual RAS inhibition reduce mortality and cardiovascular events in heart failure patients with renal dysfunction compared to monotherapy?
Effect estimate: HR 0.86
p-value: p=0.005
In patients with heart failure, dual RAS inhibition reduces the risk of CV death or HF hospitalization but significantly increases the risk of adverse events including renal impairment, hyperkalemia, and hypotension.
Supports dual RAS inhibition for CV outcomes in HF with renal dysfunction; challenges consensus against benefit but increases adverse events.
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.
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Silva et al. (2019) conducted a meta-analysis in Heart failure with renal dysfunction (n=34,131). Dual renin-angiotensin system (RAS) inhibition vs. Monotherapy was evaluated on Cardiovascular death or heart failure hospitalization in patients with renal dysfunction (HR 0.86, p=0.005). Dual RAS inhibition compared with monotherapy significantly reduced the risk of cardiovascular death or heart failure hospitalization in heart failure patients with renal dysfunction (HR 0.86, p=0.005).
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