Anti-Hypertensive Effect of Sacubitril/Valsartan: A Meta-Analysis of Randomized Controlled Trials

BACKGROUND: For elderly patients suffering from arterial hypertension, a complete assessment of the efficacy and safety of sacubitril/valsartan used as an anti-hypertensive agent is not available yet. Therefore, we decided to perform a meta-analysis of randomized controlled trials (RCTs) to explore some endpoints concerning anti-hypertensive efficacy as well as safety of sacubitril/valsartan in elderly hypertensive patients. METHODS: PubMed and Scopus have been extensively investigated with the help of some key words until June 15, 2018. The meta-analysis incorporated exclusively RCTs in which the anti-hypertensive efficacy and safety of sacubitril/valsartan were compared with those of a reference drug (comparator) that could be an angiotensin-converting enzyme inhibitor (ACEi), an angiotensin receptor blocker (ARB), a calcium channel blocker (CCB) or a beta-blocker. Continuous ambulatory blood pressure monitoring was required as an inclusion criterion in the studies to be included in the meta-analysis. The mean reductions in systolic blood pressure and diastolic blood pressure in the sitting position (msSBP and msDBP, respectively), 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 taken as safety outcomes. RESULTS: Five RCTs were included with a total of 1,513 patients for analysis. In all studies, the comparator drug was an ARB (valsartan in two cases and olmesartan in the remaining three cases). Compared with ARBs, after 12 weeks there was a significant reduction in msSBP (weight mean difference (WMD) = - 5.41 mm Hg, 95% confidence interval (CI): -7.0 to -3.8; P < 0.01), msDBP (WMD = -1.22 mm Hg, 95% CI : -2.15 to -0.3; P < 0.01), maSBP (WMD = -4.58 mm Hg, 95% CI: -5.62 to -3.54; P < 0.01) and maDBP (WMD = -2.17 mm Hg, 95% CI: - 2.78 to -1.56; P < 0.01) in elderly hypertensive patients at 12 weeks. CONCLUSIONS: Sacubitril/valsartan may reduce arterial pressure more efficaciously than ARBs in elderly hypertensive patients. These results have to be confirmed by further RCTs with a good methodological quality, possibly with a greater sample size.