Efficacy and Safety of Fimasartan/Indapamide Combination Therapy versus Fimasartan Monotherapy in Patients with Essential Hypertension Inadequately Responding to Fimasartan 30 mg (FINEDUO): A Randomized, Double-Blind, Multicenter, Phase III Study

Purpose: Effective blood pressure (BP) control in hypertension frequently requires combination therapy, particularly in patients whose BP is inadequately controlled by monotherapy. This study evaluated the efficacy and safety of fimasartan (FMS) and indapamide (IND) sustained release (SR) combination therapy. Patients and Methods: In this randomized, double-blind, phase III trial, patients with hypertension who remained uncontrolled after a 4-week run-in with FMS 30 mg, were randomized to FMS 30 mg/IND SR 1.5 mg or FMS 30 mg, followed by forced titration to FMS 60 mg/IND SR 1.5 mg or FMS 60 mg after 4 weeks. The primary endpoint was the change in sitting systolic BP (SiSBP) at week 8. Secondary endpoints included changes in sitting diastolic BP (SiDBP), BP control rates, response rates, and safety outcomes. Results: Two hundred forty-eight patients were randomized (FMS/IND SR, n=126; FMS, n=122). At week 8, the least square mean reduction in SiSBP was greater with FMS/IND SR than with FMS (− 17.9 vs − 7.4 mmHg, P < 0.0001). Significant improvements were also observed for SiSBP at week 4, SiDBP at week 4 and 8, and BP control rates and response rates. The safety profile was comparable between groups, with no significant differences in adverse events, including patients aged 65 years and older. Conclusion: FMS/IND SR combination therapy demonstrated superior antihypertensive efficacy, rapid BP control, and comparable safety to FMS monotherapy. This regimen may serve as an effective therapeutic option, particularly in elderly or high-risk hypertensive patients. Clinical Trial Registration: https://www.clinicaltrials.gov , NCT05878561. This graphical abstract summarizes the design and key findings of the FINEDUO randomized, double-blind, multicenter, phase III, 8-week trial comparing fimasartan plus indapamide sustained-release combination therapy with fimasartan monotherapy in patients with essential hypertension inadequately controlled with fimasartan. The left panel presents the study design and patient disposition. A total of 511 patients were screened; 129 failed screening, and 382 entered the fimasartan 30 mg run-in period. After 134 run-in failures, 248 patients were randomized at baseline in a 1:1 ratio. In the combination-therapy group, 126 patients received fimasartan 30 mg plus indapamide sustained-release 1.5 mg, followed by forced titration at week 4 to fimasartan 60 mg plus indapamide sustained-release 1.5 mg; 114 patients completed the study at week 8. In the monotherapy group, 122 patients received fimasartan 30 mg, followed by forced titration at week 4 to fimasartan 60 mg; 107 patients completed the study at week 8.The upper-right panel shows the blood pressure–lowering effect, expressed as least-squares mean changes from baseline in systolic and diastolic blood pressure at weeks 4 and 8. Blue bars represent fimasartan/indapamide sustained-release combination therapy, and yellow bars represent fimasartan monotherapy. At week 4, systolic blood pressure decreased by 15.3 mmHg in the combination group and by 5.0 mmHg in the monotherapy group, while diastolic blood pressure decreased by 6.0 mmHg and 1.2 mmHg, respectively; both between-group comparisons were statistically significant with P < 0.0001. At week 8, systolic blood pressure decreased by 17.9 mmHg in the combination group and by 7.4 mmHg in the monotherapy group, while diastolic blood pressure decreased by 7.5 mmHg and 2.8 mmHg, respectively; both between-group comparisons were also statistically significant with P < 0.0001.The lower-right panel summarizes safety and tolerability outcomes, including treatment-emergent adverse events and adverse drug reactions in the overall population and according to age group. In the overall population, treatment-emergent adverse events occurred in 17.74% of patients receiving fimasartan/indapamide sustained-release and 14.17% of patients receiving fimasartan monotherapy. Adverse drug reactions occurred in 12.10% and 5.83% of patients, respectively. Among patients younger than 65 years, treatment-emergent adverse events occurred in 15.15% versus 19.30%, and adverse drug reactions occurred in 10.61% versus 7.02%. Among patients aged 65 years or older, treatment-emergent adverse events occurred in 20.69% versus 9.52%, and adverse drug reactions occurred in 13.79% versus 4.76%. All safety comparisons shown in the graphical abstract had P values greater than 0.05, indicating no statistically significant differences between treatment groups.Graphical abstract summarizing the study design, blood pressure–lowering efficacy, and safety outcomes. In patients with essential hypertension inadequately controlled with fimasartan, fimasartan/indapamide sustained-release combination therapy produced significantly greater reductions in systolic and diastolic blood pressure than fimasartan monotherapy at weeks 4 and 8, with no statistically significant differences in adverse-event rates. Keywords: blood pressure control, combination therapy, fimasartan, indapamide sustained release, hypertension