A meta‐analysis investigating the efficacy and adverse events linked to sacubitril‐valsartan in various heart failure subtypes

Q: What is the clinical evidence from this study?

Study design: Meta-Analysis. Population: Heart failure (HFrEF, HFmrEF, HFpEF) (n=15939). Intervention: Sacubitril-valsartan vs. ACE inhibitors or ARBs. Primary outcome: All-cause mortality in patients with HFrEF (RR 0.85, 95% CI 0.78-0.93, p=0.0004).

Qing Ji

doi:10.1002/clc.24192

November 27, 2023Clinical CardiologyOpen Access

A meta‐analysis investigating the efficacy and adverse events linked to sacubitril‐valsartan in various heart failure subtypes

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Key result

Sacubitril-valsartan reduces all-cause mortality ~15% vs. ACE inhibitors or ARBs in HFrEF.

RR 0.85
95% CI 0.78-0.93
P=0.0004
n=15,939

Figures

Graphical abstract published by Clinical Cardiology — Graphical abstract · Published by Clinical Cardiology · CC BY

Why the study?

Sacubitril-valsartan has been purported to exhibit superiority over ACE inhibitors and ARBs in heart failure, prompting an updated meta-analysis across different heart failure subtypes.

Does sacubitril-valsartan reduce mortality and heart failure hospitalizations compared to ACE inhibitors or ARBs in adult patients with various subtypes of heart failure?

Study Design

Type

Meta-Analysis (n=15,939)

Multicenter

Yes

Structured PICO

Does sacubitril-valsartan reduce mortality and heart failure hospitalizations compared to ACE inhibitors or ARBs in adult patients with various subtypes of heart failure?

P

Population

15,939 adult patients with varying heart failure subtypes across 9 randomized controlled trials comparing the efficacy and safety of sacubitril-valsartan to ACE inhibitors or ARBs over 3 to 35 months of follow-up.

I

Intervention

Sacubitril-valsartan administered orally, predominantly at a dose of 200 mg bid (sacubitril 97 mg and valsartan 103 mg), with one trial using 100 mg bid.

C

Comparator

ACE inhibitors (enalapril 10 mg bid, or 5 mg bid in one trial) or ARBs (valsartan 160 mg bid).

O

Outcome

All-cause mortality, cardiovascular mortality, and heart failure hospitalization events.hard clinical

Main Result

Relative Risk: 0.85 (95% CI 0.78–0.93)

p-value: p=0.0004

Sacubitril-valsartan significantly reduces all-cause and cardiovascular mortality in patients with HFrEF compared to standard ACEi/ARB therapy, though it carries a higher risk of hypotension.

Limitations

Most trials were sponsored by a drug company
Low number of included studies
Variations in gender, age, HF type, baseline blood pressure, comparator, and follow-up time among trials
Inadequate follow-up time in some trials to capture long-term adverse events
Most included trials were sponsored by a drug company, adding potential bias.
Low number of studies, making it difficult to assess publication bias.
Not all outcomes were reported for each trial.
Variation in patient baseline characteristics (gender, age, HF type, blood pressure) and follow-up times among trials.
Inadequate follow-up time in some trials to capture long-term adverse events.

Implication

Supports sacubitril-valsartan preference in HFrEF for mortality reduction; confirms pooled RCT benefit with hypotension caution.

Abstract

BACKGROUND: Sacubitril-valsartan, an inhibitor of the angiotensin receptor neprilysin (ARNi), has been purported to exhibit superiority over angiotensin converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARBs) in individuals diagnosed with heart failure. HYPOTHESIS: This paper gives an updated meta-analysis comparing the efficacy and safety of sacubitril-valsartan to that of standard treatment for different types of heart failure. RESULTS: The meta-analysis comprised a total of nine randomized controlled trials (RCTs), incorporating data from a substantial sample size of 15 939 patients. The study observed a decrease in overall mortality and mortality related to cardiovascular causes among patients in the heart failure with reduced ejection fraction (HFrEF) category who were treated with sacubitril-valsartan. However, no statistically significant variation in this outcome was seen among patients with heart failure with preserved ejection fraction and HFmrEF. Patients who were administered sacubitril-valsartan had a notably elevated likelihood of experiencing hypotension. Nevertheless, no significant disparities were observed in terms of other adverse events among the various treatment groups. CONCLUSION: Current meta-analysis provide support for use of sacubitril-valsartan in decreasing mortality in patients with HFrEF. However, more numbers of studies are required to draw a definite conclusion on other benefits associated with sacubitril-valsartan use over standard treatment of ACE inhibitors and ARBs.

Discussion

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Cite This Study

Qing Ji (2023) conducted a meta-analysis in Heart failure (HFrEF, HFmrEF, HFpEF) (n=15,939). Sacubitril-valsartan vs. ACE inhibitors or ARBs was evaluated on All-cause mortality in patients with HFrEF (RR 0.85, 95% CI 0.78-0.93, p=0.0004). Sacubitril-valsartan significantly reduced all-cause mortality by 15% (RR 0.85, 95% CI 0.78-0.93, p=0.0004) compared to ACE inhibitors or ARBs in patients with heart failure with reduced ejection fraction.

synapsesocial.com/papers/6a23a12a9ed8aa0626a02e64 https://doi.org/10.1002/clc.24192

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A meta‐analysis investigating the efficacy and adverse events linked to sacubitril‐valsartan in various heart failure subtypes

Figures

Study Design

Structured PICO

Main Result

Limitations

Implication

Abstract

Discussion

Cite This Study

A meta‐analysis investigating the efficacy and adverse events linked to sacubitril‐valsartan in various heart failure subtypes

Figures

Study Design

Structured PICO

Main Result

Limitations

Implication

Abstract

Discussion

Cite This Study

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