Comparative assessment of arterial stiffness and endothelial dysfunction during treatment with fixed combinations of antihypertensive drugs in patients with arterial hypertension and coronary artery disease

Aim. To evaluate and compare the efficacy and safety of two triple fixed combinations (FC) of antihypertensive drugs, amlodipine/indapamide/perindopril and amlodipine/valsartan/hydrochlorothiazide (HCTZ), in managing the clinical course in patients with grade 2-3 hypertension and functional class II and III coronary artery disease.

Materials and methods. The study included 52 patients with uncontrolled hypertension with systolic blood pressure (SBP)≥160 mmHg and/or diastolic blood pressure (DBP)≥90 mmHg combined with stable effort angina who were taking two antihypertensive drugs at the beginning of the study. Depending on the treatment, the participants were divided into two groups: Group 1 included 27 subjects who received FC of amlodipine/indapamide/perindopril, and Group 2 included 25 subjects who received FC of amlodipine/valsartan/HCTZ. All patients also received β-blocker bisoprolol 5-10 mg and antiplatelet agent 75-100 mg.

Results. After 12 weeks of follow-up compared to baseline, there was a significant decrease in office BP in Groups 1 and 2: SBP by 34.50 and 32.03 mmHg (p<0.001 for both groups), with significant differences between the groups (p=0.045), DBP by 13.28 and 13.79 mmHg, respectively (p<0.001 for both groups), without significant differences between the groups (p=0.052). The heart rate decreased in both groups to 69.00 bpm, with no intergroup differences (p=0.061). In Groups 1 and 2, after 12 weeks of follow-up, arterial stiffness significantly improved compared to baseline: SBP in the aorta decreased by 23.50 and 27.00 mmHg (p<0.001 for both groups), DBP in the aorta decreased by 17.50 and 20.00 mmHg (p<0.001 for both groups), pulse pressure in the aorta decreased by 4.50 and 8.00 mmHg (p<0.001), augmentation index decreased by 9.00% and 10.00% (p<0.001 for both groups), pulse wave velocity decreased by 2.51 and 1.97 m/s (p<0.001 for both groups), with significant differences between groups (p=0.032), the ankle-brachial index decreased by 0.01 and 0.02 (p<0.001 for both groups), vascular age decreased by 5.00 years (p=0.001) and 3.00 years (p=0.025) [p=0.025 for comparison between groups], endothelial function improved by 24.5% (p=0.015) and 18.0% (p<0.001) [p=0.015 for comparison between groups]. The number of ischemia episodes significantly decreased in both groups: in Group 1 from 2.8±0.3 to 1.2±0.2 per week (p=0.021), in Group 2 from 2.5±0.6 to 1.5±0.3 (p=0.018), with no significant differences between the groups.

Conclusion. Both triple FCs – amlodipine/indapamide/perindopril and amlodipine/valsartan/HCTZ – effectively reduced office BP and improved vascular stiffness and endothelial function in patients with hypertension and coronary artery disease. FC of amlodipine/indapamide/perindopril provided a more pronounced reduction in office SBP, pulse wave velocity, and vascular age, as well as endothelial function improvement. Both regimens reduced the incidence of ischemic episodes, with no significant differences between the groups.