Comparison between sacubitril/valsartan and thiazide diuretics among patients with uncontrolled hypertension in Japan

Although renin-angiotensin system (RAS) inhibitors and calcium channel blockers are widely used to treat hypertension in Japan, <10% of patients use thiazides. This study aimed to evaluate differences in the efficacy and safety of sacubitril/valsartan and thiazide diuretics. Patients with poor blood pressure (BP) control, despite combination treatment with RAS inhibitors and calcium channel blockers, were included in the study. Patients treated with thiazides (THZ group, n = 306) and those who switched from RAS inhibitors to sacubitril/valsartan (SacVal group, n = 433) were compared. Propensity score analysis with inverse probability weighting was performed. A significantly higher target BP achievement rate was observed in the SacVal group than in the THZ group (4 months, 37% vs. 26%, p < 0.001). In a general linear mixed model, significant decreases in office and home BP were observed in both groups (p < 0.001); however, no significant interaction effects were observed between the drug type and time course. Discontinuation of the treatment by adverse events was significantly more frequent in THZ group (10%) than in SacVal group (3%), with a hazard ratio [95% confidence interval] of 3.47 [1.78, 6.76] (p < 0.001). In the model using the propensity score, compared with THZ group, significantly lower levels of office and home systolic BP, uric acid, glycated hemoglobin A_1c, and higher levels of eGFR were observed in SacVal group (p = 0.04, 0.002, <0.001, 0.01, and 0.02, respectively). In conclusion, comparable BP reduction and positive effects on metabolic parameters were observed with sacubitril/valsartan treatment, with better treatment tolerability than thiazide diuretics.