Abstract 4369346: Comparative effects of Single-Pill Combinations on Arterial Stiffness and Central Blood Pressure: A Randomized Trial in Indian Adults with Hypertension

I ntroduction: Arterial stiffness and central arterial pressure are independent predictors of cardiovascular morbidity and mortality, with central pressure offering prognostic value beyond peripheral blood pressure (BP). While current guidelines recommend initiating treatment with single-pill combinations (SPCs), but the comparative effects of these combinations on arterial stiffness and central BP remain unclear, and no randomized evidence exists demonstrating their superiority, particularly in South Asian populations. This sub-study of the TOPSIN Trial aimed to evaluate the impact of three SPCs on aortic stiffness and central BP in Indian hypertensive patients. Methods: This is a triple-blind, randomized, three-arm trial involving 210 hypertensive patients aged 30–79 years. Participants were randomized in a 1:1:1 ratio to receive one of the following SPCs: amlodipine + perindopril (AM+PE), perindopril + indapamide (PE+ID), or amlodipine + indapamide (AM+ID). Eligible patients had clinic SBP≥140 and <160 mmHg on one antihypertensive or SBP ≥150 and <180 mmHg with no prior treatment. The study assessed central arterial stiffness- carotid-femoral pulse wave velocity (cf-PWV), carotid β-stiffness index (SI beta); carotid systolic (cSBP), diastolic (cDBP), and pulse pressure (cPP) using validated vascular analyzer (ArtSens-Plus, India). Secondary measures included 24-hour ambulatory BP (24ABPM), plasma nitric oxide concentration (NOx), and oxidative stress markers. SPCs were initiated at standard doses with forced up-titration at 2 months, and efficacy was assessed at 6 months. Results: Of the 210 randomized participants, 184 (38.0% women) aged 51±9.89 years were included in the final analysis. The mean 24h ambulatory SBP was 137.5±15.4 mmHg, and DBP was 85.3±9.1 mmHg. 53.3% had a history of hypertension, and 16.3% had diabetes. All three SPCs significantly reduced central and peripheral BP (p<0.001), but no significant between-group differences were observed. There were no significant changes in arterial stiffness. However, AM+PE and PE+ID combinations significantly improved NOx levels (p<0.01), while oxidative stress and antioxidant capacity remained unchanged across groups. Conclusion: All three single-pill combinations effectively reduced central and peripheral BP in Indian hypertensive patients, with no significant differences in arterial stiffness. Combinations containing perindopril improved nitric oxide levels, suggesting additional vascular benefits.