Abstract

Background: The management of hypertension remains suboptimal throughout the world. Methods: We performed a random-effects model meta-analysis of randomized controlled trials to determine the effectiveness and safety of sacubitril/valsartan (LCZ696) for the treatment of high arterial pressure. Relevant published articles from PubMed, Cochrane base, and Medline were examined, and the last search date was December 2020. Only published randomized controlled trials and double-blind studies were selected for further analysis. The mean reductions in systolic blood pressure (msSBP) and diastolic blood pressure (msDBP) in the sitting position, as well as the mean reductions in ambulatory systolic blood pressure (maSBP) and ambulatory diastolic blood pressure (maDBP), were assumed as efficacy endpoints. Adverse events (AEs) were considered as safety outcomes. Results: Ten studies with a total of 5931patients were included for analysis. Compared with placebo, LCZ696 had a significant reduction in msSBP (weight mean difference (WMD) = −6.52 mmHg, 95% confidence interval (CI): −8.57 to −4.47; p < 0.001), msDBP (WMD = −3.32 mmHg, 95% CI: −4.57 to −2.07; p < 0.001), maSBP (WMD = −7.08 mmHg, 95% CI: −10.48 to −3.68; p < 0.001), maDBP (WMD = −3.57 mmHg, 95% CI: −5.71 to −1.44, p < 0.001). In subgroup analysis, only 200 mg and 400 mg LCZ696 showed a significant BP reduction. There was no difference in the AE rate between the LCZ696 and placebo groups (WMD = 1.02, 95% CI: 0.83 to 1.27, p = 0.54). Egger’s test revealed a potential publication bias for msSBP (p = 0.025), but no publication bias for other outcomes. Conclusion: LCZ696 may reduce blood pressure more efficaciously than traditional therapy in hypertensive patients without increasing adverse effects.

Highlights

  • Hypertension is a well-known and modifiable risk factor for cardiovascular disease worldwide

  • Omapatrilat resulted in superior effects on systolic blood pressure and pulse pressure reduction than enalapril [6], but was not approved due to the unacceptable rate of angioedema

  • The main outcomes were the difference in the means of the blood pressure between LCZ696 and traditional therapy

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Summary

Introduction

Hypertension is a well-known and modifiable risk factor for cardiovascular disease worldwide. Several randomized controlled trials (RCTs) have attempted to compare the antihypertensive efficacy and safety of LCZ696 in hypertensive patients [7,8,9,10,11,12,13,14,15,16]. Most of these prospective and double-blind clinical trials showed that LCZ696 achieved the target blood pressure better without significant adverse effects. We performed a meta-analysis including high quality RCTs to precisely determine the effectiveness and safety of LCZ696 for the treatment of high arterial pressure

Materials and Methods
Data Synthesis and Statistical Analyses
Angioedema in each group
Antihypertensive Effectiveness of LCZ696
Mechanisms of LCZ696
Clinical Implications
Findings
Limitations

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