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Meta-Analysis
. 2020 Nov;7(2):e001294.
doi: 10.1136/openhrt-2020-001294.

Beneficial and harmful effects of sacubitril/valsartan in patients with heart failure: a systematic review of randomised clinical trials with meta-analysis and trial sequential analysis

Emil Eik Nielsen  1   2 , Joshua Buron Feinberg  3   2 , Fan-Long Bu  4 , Michael Hecht Olsen  3   2   5 , Ilan Raymond  3 , Frank Steensgaard-Hansen  3 , Janus Christian Jakobsen  2   6
Affiliations
Meta-Analysis

Beneficial and harmful effects of sacubitril/valsartan in patients with heart failure: a systematic review of randomised clinical trials with meta-analysis and trial sequential analysis

Emil Eik Nielsen et al. Open Heart. 2020 Nov.

Abstract

Current guidelines recommend angiotensin receptor blocker neprilysin inhibitors (ARNI) (sacubitril/valsartan) as a replacement for angiotensin-converting-enzymeinhibitor (ACE-I) in heart failure with reduced ejection fraction (HFrEF) who remain symptomatic despite optimal medical therapy. The effects of ARNIs have not previously been assessed in a systematic review. We searched for relevant trials until October 2019 in CENTRAL, MEDLINE, Embase, LILACS, BIOSIS, CNKI, VIP, WanFang and CBM. Our primary outcomes were all-cause mortality and serious adverse events. We systematically assessed the risks of random errors and systematic errors. PROSPERO registration: CRD42019129336. 48 trials randomising 19 086 participants were included. The ARNI assessed in all trials was sacubitril/valsartan. ACE-I or ARB were used as control interventions. Trials randomising HFrEF participants (27 trials) and heart failure with preserved ejection fraction (HFpEF) participants (four trials) were analysed separately. In HFrEF participants, meta-analyses and Trial Sequential Analyses showed evidence of a beneficial effect of sacubitril/valsartan when assessing all-cause mortality (risk ratio (RR), 0.86; 95% CI, 0.79 to 0.94) and serious adverse events (RR, 0.89; 95% CI, 0.86 to 0.93); and the results did not differ between the guideline recommended target population and HFrEF participants in general. We found no evidence of an effect of sacubitril/valsartan in HFpEF participants. Sacubitril/valsartan compared with either ACE-I or ARB seems to have a beneficial effect in patients with HFrEF. Our results indicate that sacubitril/valsartan might be beneficial in a wider population of patients with heart failure than the guideline recommended target population. Sacubitril/valsartan does not seem to show evidence of a difference compared with valsartan in patients with HFpEF.

Keywords: heart failure; heart failure treatment; renin-angiotensin system.

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Conflict of interest statement

Competing interests: None declared.

Figures

Figure 1
Figure 1
PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analysis) flow diagram.
Figure 2
Figure 2
Risk of bias summary.
Figure 3
Figure 3
Forest plot of subgroup based on type of heart failure on all-cause mortality.
Figure 4
Figure 4
Forest plot of participants with heart failure with reduced ejection fraction on all-cause mortality.
Figure 5
Figure 5
Trial sequential analysis of participants with heart failure with reduced ejection fraction on all-cause mortality.
Figure 6
Figure 6
Forest plot of participants with heart failure with reduced ejection fraction on serious adverse events.
Figure 7
Figure 7
Trial sequential analysis of participants with heart failure with reduced ejection fraction on serious adverse events.
Figure 8
Figure 8
Forest plot of participants with heart failure with preserved ejection fraction on all-cause mortality.
Figure 9
Figure 9
Trial sequential analysis of participants with heart failure with preserved ejection fraction on all-cause mortality.
See this image and copyright information in PMC

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