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Randomized Controlled Trial
. 2025 Sep;31(9):3169-3175.
doi: 10.1038/s41591-025-03854-w. Epub 2025 Jul 25.

Comparison of dual therapies for hypertension treatment in India: a randomized clinical trial

Dorairaj Prabhakaran #  1 , Ambuj Roy #  2 , Ambalam M Chandrasekaran  3 , Dimple Kondal  3 , Somnath Mukherjee  3 , Gaia Kiru  4 , Kavita Singh  5 , Hyndavi Salwa  3 , Edmin Christa Sobitharaj  3 , Ameeka Shereen Lobo  3 , Gayatri Mahajan  3 , Bishav Mohan  6 , Aman Khanna  7 , Amit Malviya  8 , Satish G Patil  9 , Vinod K Abichandani  10 , Bhupinder Singh  11 , Bal Kishan Gupta  12 , Balsubramaiam Yellapantula  13 , Shailendra Dandge  14 , Shantanu Sengupta  15 , Sunil Kumar  16 , Neil Bardoloi  17 , Nagendra Boopathy Senguttuvan  18 , Rakesh Kumar Sahay  19 , Suvarna Patil  20 , Surender Deora  21 , Rajpurohit Prahalad  22 , Vijaya Parthasaradhi Sarvepalli  23 , Justin Paul Gnanaraj  24 , Mallika Khanna  7 , Animesh Mishra  8 , Kiran Aithal  9 , Vipul Chavda  10 , Victoria R Cornelius  4 ; TOPSPIN Clinical Consortia; Neil R Poulter  4
Collaborators, Affiliations
Randomized Controlled Trial

Comparison of dual therapies for hypertension treatment in India: a randomized clinical trial

Dorairaj Prabhakaran et al. Nat Med. 2025 Sep.

Abstract

Evidence is lacking for guiding optimal combination hypertension therapy in South Asian patients. Here we investigated the blood pressure (BP)-lowering efficacy and safety of three commonly recommended antihypertensive dual combinations in a multicenter, single-blinded trial conducted in India. We randomized Indians aged 30-79 years (mean age, 52 years) with mean sitting systolic blood pressure (SBP) of 150-179 mmHg on no treatment or an SBP of 140-159 mmHg on monotherapy 1:1:1 to a single-pill combination of amlodipine-perindopril, perindopril-indapamide or amlodipine-indapamide. The primary outcome was the mean change in 24-hour ambulatory SBP at 6 months. Of the 1,981 participants (42% females) enrolled in the trial, 1,637 completed a 24-hour ambulatory BP measurement. All three drug combinations produced similar large reductions in the primary outcome, namely ambulatory (~14/8 mmHg) and office (~30/14 mmHg) BPs after 6 months, such that hypertension control rates (sitting BP < 140/90 mmHg) were achieved in approximately 70% of participants in all three groups. Furthermore, no significant differences in secondary outcomes, such as mean day and night ambulatory and office BPs and hypertension control rates, were observed among the study groups. Thus, in Indian patients, amlodipine-perindopril, perindopril-indapamide and amlodipine-indapamide were all equally well tolerated and equally highly effective in reducing 24-hour ambulatory and office BPs (ClinicalTrials.gov registration: NCT05683301 ).

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Conflict of interest statement

Competing interests: N.P. has received financial support from several pharmaceutical companies that manufacture BP-lowering agents. N.P. has received consultancy fees (Servier and Aktiia), funding for research projects and staff (Servier and Pfizer) and fees for arranging and speaking at educational meetings (AstraZeneca, Lri Therapharma, Napi, Servier, Sanofi, Eva Pharma, Pfizer, Emcure India, Dr. Reddy’s Laboratories and Zydus). He holds no stocks or shares in any such company. D.P.’s institution, the Centre for Chronic Disease Control, has received research grants from Sun Pharmaceuticals, Lupin Limited and Intas Pharmaceuticals in India for capacity building of primary care physicians in cardiovascular diseases. The other authors declare no competing interests.

Figures

Fig. 1
Fig. 1. Design and follow-up of the TOPSPIN trial.
The CONSORT flow diagram of the TOPSPIN trial. PI, principal investigator.
Fig. 2
Fig. 2. Unadjusted mean change in BP.
a–d, Bar graphs with error bars showing ambulatory SBP (a), ambulatory DBP (b), office SBP (c) and office DBP (d). In c and d, the bars represent mean change in BP at 2 months, 4 months and 6 months. Error bars denote 95% CI.
Extended Data Fig. 1
Extended Data Fig. 1. Changes in Ambulatory Systolic Blood Pressure by Pre-Specified Sub-Groups.
Plots showing mean difference with 95% CI and p-value for interaction.
Extended Data Fig. 2
Extended Data Fig. 2. Changes in Ambulatory Diastolic Blood Pressure by Pre-Specified Sub-Groups.
Plots showing mean difference with 95% CI and p-value for interaction.
See this image and copyright information in PMC

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