Efficacy and safety of sacubitril/valsartan in the treatment of middle-aged and elderly patients with hypertension: a systematic review and meta-analysis of randomized controlled trials

Background: With the increase of hypertensive patients worldwide, the need for better antihypertensive drugs to achieve blood pressure standards and reduce complications is of great clinical significance. As an angiotensin receptor-neprilysin inhibitor, sacubitril/valsartan has been widely used in the treatment of heart failure, but its efficacy and safety in the treatment of middle-aged and elderly hypertensive patients are still controversial. Therefore, we performed a meta-analysis to compare the efficacy and safety of sacubitril/valsartan and other antihypertensive drugs in the treatment of middle-aged and elderly patients with hypertension. Methods: The databases of PubMed, Embase, and Web of Science were systematically searched from their establishment to February 2022 to collect the randomized controlled trials (RCTs) of sacubitril/valsartan and other antihypertensive drugs in the treatment of middle-aged and elderly hypertensive patients. The Cochrane Collaboration's tool was used to assess risk of bias for included studies, and the meta-analysis was performed by using RevMan 5.3. Results: In all, 7 studies which met the criteria were included, with a total sample size of 3,323 patients, including 1,899 patients treated with sacubitril/valsartan, and 1,424 patients treated with angiotensin II receptor blockers (ARBs). The meta-analysis showed that compared with other antihypertensive drugs, sacubitril/valsartan can significantly reduce mean reductions in sitting systolic blood pressure [mean difference (MD) =-4.70, 95% confidence interval (CI): -5.79 to -3.61, P<0.001], mean reductions in sitting diastolic blood pressure (MD =-2.29, 95% CI: -2.53 to -2.04, P<0.001), 24-hour mean reductions in ambulatory systolic blood pressure (MD =-3.36, 95% CI: -4.08 to -2.64, P<0.001), and 24-hour mean reductions in ambulatory diastolic blood pressure (MD =-1.49, 95% CI: -1.99 to -0.99, P<0.001), while there was no significant difference in the incidence of adverse events [odds ratio (OR) =1.14, 95% CI: 1.00 to 1.31, P=0.06], serious adverse events (OR =1.06, 95% CI: 0.64 to 1.76, P=0.81), and discontinuations due to adverse events (OR =0.86, 95% CI: 0.51 to 1.46, P=0.58). Discussion: Compared with other antihypertensive drugs, sacubitril/valsartan may be more effective in lowering blood pressure, and its safety may be comparable to that of ARBs. However, these results have to be confirmed by future RCTs with larger sample sizes and higher quality, and the long-term benefits of sacubitril/valsartan require further observation.