Sacubitril/valsartan shows greater LVMI regression than some antihypertensives in hypertension with remodeling

ObjectiveTo systematically evaluate the relative efficacy and impact on cardiac function of sacubitril/valsartan (Sac/Val) vs. active antihypertensive comparators represented in the eligible evidence base for reversing left ventricular hypertrophy (LVH) in patients with hypertension using network meta-analysis.MethodsPubMed, Embase, The Cochrane Library, CNKI, Wanfang Data, and SinoMed databases were searched from inception to December 2025 for randomized controlled trials (RCTs) evaluating sacubitril/valsartan vs. active antihypertensive comparators in patients with essential hypertension and cardiovascular remodeling. The primary outcome was the change in left ventricular mass index (LVMI). Network meta-analysis was performed using STATA 18.0 software based on the frequentist framework. Given the clinical heterogeneity in imaging assessment modalities, a random-effects model was employed to calculate the weighted mean difference (MD) and 95% confidence intervals (CI). The surface under the cumulative ranking curve (SUCRA) was used as a supportive ranking metric, whereas comparative interpretation primarily relied on effect estimates and their confidence intervals.ResultsEleven RCTs involving 851 patients were included. The network meta-analysis showed that Sac/Val achieved greater LVMI regression than Amlodipine (MD = −22.54 g/m2, 95% CI: −40.23, −4.86) and Valsartan (MD = −11.34 g/m2, 95% CI: −21.45, −1.23) in reversing LVMI. Compared with Enalapril and Olmesartan, Sac/Val also showed numerically greater LVMI regression, but these differences were not statistically significant. Sac/Val had the highest SUCRA value (96.4%); however, rankings were interpreted descriptively only, while comparative interpretation was primarily based on effect sizes and confidence intervals. Secondary outcome analysis indicated that while Sac/Val effectively reduced systolic and diastolic blood pressure, it had no significant impact on left ventricular ejection fraction (LVEF) (P > 0.05).ConclusionIn hypertensive patients with cardiovascular remodeling, sacubitril/valsartan was associated with greater LVMI regression than amlodipine and valsartan within the current network, whereas comparisons with enalapril and olmesartan remained inconclusive. Given the substantial heterogeneity, evidence of network incoherence, and low-to-very-low certainty of the main comparisons, these results should be regarded as tentative rather than definitive.Systematic Review RegistrationPROSPERO CRD420261281426.