Abstract Objective To conduct a comparative assessment of the six-month cardioprotective efficacy of combined therapy using azilsartan with indapamide and nitrendipine in patients with essential hypertension (EH). Materials and Methods The study included 101 male and female patients with grade I–II arterial hypertension (AH) according to the classification (ESC/ESH, 2018), who were undergoing outpatient treatment at the Republican Specialized Scientific-Practical Medical Center of Cardiology. The mean age of the patients was 53.1±11.2 years, and the mean duration of AH was 8.5±7.2 years. Initially and after 6 months of therapy, echocardiography was performed to determine the left ventricular myocardial mass index (LVMMI) and left ventricular (LV) echo geometry types. Echocardiography (ECHO) was performed using the "En VisorC" ultrasound system (Philips, Netherlands). Statistical significance was considered for all analyses with p <0.05. Results All patients were divided into 2 groups: Group 1 - patients on combined antihypertensive therapy (AHT) with azilsartan and indapamide (n=50) and Group 2 - patients on therapy with azilsartan and nitrendipine (n=51). The mean daily dose of azilsartan was 49.3±6.0 mg, nitrendipine was 10.88±4.3 mg, and indapamide was 1.69±0.5 mg. In Group 1, the LVMMI initially was 127.4±32.9 g/m2, and after treatment, it was 110.3±29.0 g/m2 (p<0.001); in Group 2, it was 138.7±31.9 g/m2 and 116.6±30.3 g/m2, respectively (p<0.001). The degree of LVMMI reduction in Group 1 was -13.3±15.6% compared to Group 2, which was -14.4±17.9% (p>0.05). During therapy with azilsartan, indapamide, and nitrendipine, the reduction of LVMMI in EH patients was associated with a decrease in the concentric type of left ventricular hypertrophy (LVH) in both therapy groups: in both groups, a significant increase in the LV diastolic filling pattern index/LVMMI was observed, which was 0.51±0.07 ml/g before treatment and 0.57±0.14 ml/g after treatment in Group 1 (p<0.001), and 0.50±0.11 ml/g before treatment and 0.54±0.12 ml/g after treatment in Group 2 (p<0.02). Significant regression of LVH with 6-month combined therapy in both groups was accompanied by an improvement in LV echo geometry. Initially, there were 12 patients (11.9%) with unchanged LV echo geometry, concentric remodeling was detected in 9 patients (8.91%), eccentric LVH in 30 patients (29.7%), and concentric LVH in 50 patients (49.5%). In the dynamics, the number of patients with normal LV echo geometry increased to 41 patients (40.6%), with concentric LVH decreased to 34 patients (33.6%), with concentric remodeling decreased to 7 patients (7%), and with eccentric LVH decreased to 19 patients (18.8%) (χ2=21.635, p<0.001). Conclusion Achieving target blood pressure levels provided high cardioprotective efficacy of combined therapy with azilsartan, indapamide, and nitrendipine with improvement in LV echo geometry in both groups.