Abstract Body (Do not enter title and authors here): Introduction
The burden of over 300 million individuals living with hypertension in India is increasing steadily. Most current guidelines recommend initial combination therapy for effective blood pressure (BP) control. However, there is no randomised evidence to inform which combinations to use in South Asian populations which account for over one-quarter of the world’s population. Evidence from other ethnicities may not be relevant to this population and hence the TOPSPIN trial was initiated.
Methods
The TOPSPIN is a randomised, multi-centre, single-blind, three-arm trial of single-pill combinations (SPCs) of two BP-lowering agents. Males or females aged 18 to 79 years with a systolic BP (SBP) of ≥140mmHg and <160mmHg on one BP-lowering agent or SBP of ≥150mmHg and <180 mmHg on no BP-lowering agent were eligible. Patients with established cardiovascular disease, cerebrovascular disease and renal impairment were excluded. Participants were randomized 1:1:1 to receive a SPC of starting doses of either - amlodipine and perindopril or perindopril and indapamide or amlodipine and indapamide. Initial doses were force titrated to full doses at two months unless the SBP was <120 mmHg. The primary outcome is 24-hour ambulatory SBP at six months adjusted for baseline levels. Secondary endpoints include ambulatory diastolic BP, daytime and nighttime BP and 24-hour BP variability, clinic BP at two, four and six months, proportion of participants achieving BP control and safety endpoints The study has 85% power with 1968 participants to detect a clinically meaningful difference of 3mmHg in 24-hour SBP amongst the three groups (assuming 15% loss to follow-up and alpha-0.0167).
Results
Between 2022 to 2024, we enrolled 1981 participants (42% female, median age 52 years) from 35 hospitals across India. At recruitment, 55% of study participants were taking BP-lowering medication, 18.6% reported having diabetes and 6.2% were current smokers. Follow-up will be completed in August 2024 and the database will be locked in September 2024. Final study results will be available for presentation at the AHA meeting along with simultaneous publication.
Conclusion
TOPSPIN is the first randomized evaluation of commonly used combination therapies in a South Asian population. The results of this trial may have major clinical implications for improving BP control in India and the South Asian diaspora. (CTRI/2022/04/042106 & NCT05683301)