Key result
Sacubitril-valsartan showed no difference in serious adverse events compared to active controls (RR 0.93; 95% CI 0.86-1.01), but reduced discontinuation due to AEs and increased hypotension risk.
Why the study?
Sacubitril-valsartan is a recently approved drug, but data regarding its safety issues are limited.
Does sacubitril-valsartan affect the risk of adverse events compared to standard therapy or placebo?
Meta-Analysis (n=22,510)
Does sacubitril-valsartan affect the risk of adverse events compared to standard therapy or placebo?
Relative Risk: 0.93 (95% CI 0.86–1.01)
Sacubitril-valsartan is generally as safe and tolerable as active controls, with a lower rate of discontinuation due to adverse events but a higher risk of hypotension and long-term angioedema.
Sacubitril-valsartan shows comparable safety to controls with fewer discontinuations; extends RCT evidence by confirming higher hypotension risk and long-term angioedema signal.
Introduction: Sacubitril-valsartan is a recently approved drug. However, there are few data regarding safety issues. We aimed to summarize the available evidence regarding sacubitril-valsartan’s safety and tolerability.Methods: We conducted a systematic review with meta-analysis of randomized controlled trials (RCTs) enrolling patients receiving sacubitril-valsartan for any condition, compared with standard therapy or placebo. Database search was performed in October 2019. Outcomes were adverse events (AEs), serious AEs (SAEs), discontinuation due to AEs, and five AEs of special interest. Data were reported using risk ratio (RR) and 95% confidence interval (95%CI).Results: We included 20 RCTs (22510 participants). When compared with active controls, there were no differences in SAEs (RR=0.93, 95%CI 0.86–1.01) and AEs (RR=1.00, 95%CI 0.97–1.03). However, sacubitril-valsartan resulted in an 8% risk reduction in discontinuation due to AEs (95%CI 0.85–0.99) and an increased risk of hypotension (RR=1.45, 95%CI 1.27–1.67). The risk of angioedema was higher with follow-ups greater than 12 months (RR=2.36, 95%CI 1.29–4.33). There were no further significant differences in the remaining AEs' risk.Conclusions: Sacubitril-valsartan was at least as safe and tolerable as active control, with a similar need of administration cautiousness, except for a higher risk of hypotension. However, one should consider the study’s limitations.
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Pereira et al. (2021) conducted a meta-analysis in any condition (n=22,510). Sacubitril-valsartan vs. standard therapy or placebo was evaluated on serious adverse events (SAEs) (RR 0.93, 95% CI 0.86-1.01). Sacubitril-valsartan showed no difference in serious adverse events compared to active controls (RR 0.93; 95% CI 0.86-1.01), but reduced discontinuation due to AEs and increased hypotension risk.
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