Angiotensin receptor neprilysin inhibitor for the treatment of hypertension: a systematic review and meta-analysis

Abstract

There is substantial evidence demonstrating that angiotensin receptor neprilysin inhibitors (Sacubitril/Valsartan – Sac/Val) significantly reduce sitting blood pressure (BP). However, comprehensive pooled analyses evaluating their effects on out-of-office BP in patients with systemic hypertension remain limited. We conducted a systematic literature search of PubMed, Cochrane Library, Scopus, Embase, and ClinicalTrials.gov for randomized and non-randomized studies comparing Sac/Val with other antihypertensive agents in the treatment of systemic hypertension, from inception to the end of May 2024. Outcomes included nighttime, daytime and 24-h mean ambulatory (ma) systolic/diastolic BP (maSBP/maDBP), ambulatory pulse pressure (PP), and office BP. Safety outcomes were also assessed. Fifteen randomized controlled trials (RCTs) and 4 observational studies representing 7548 patients were included. In RCTs, Sac/Val therapy was associated with greater reductions in out-of-office blood pressure compared to angiotensin receptor blockers (ARBs) and calcium channel blockers (CCBs). This included nighttime maSBP (mean difference [MD] −3.61 mmHg; 95% confidence intervals [CI] −4.86 to −2.36; p < 0.001) and maDBP (−2.11 mmHg; [−2.69 to −1.53]; p < 0.001); as well as daytime maSBP (−3.39 mmHg; [−4.58 to −2.21]; p < 0.001) and maDBP (−1.82 mmHg; [−2.82 to −0.82]; p < 0.001). Similarly, significant reductions in 24-h maSBP/maDBP, ambulatory PP, and office BP were observed with Sac/Val. Observational studies also demonstrated that Sac/Val significantly reduced office BP compared with ARBs and thiazide diuretics (p < 0.05). There were no significant differences in the incidence of adverse events between groups. In conclusion, Sac/Val effectively reduces both out-of-office and office BP and is well tolerated throughout the follow-up period.