A landmark randomized clinical trial led by the All India Institute of Medical Sciences (AIIMS) has demonstrated that three widely used two-drug combination therapies for hypertension show equal effectiveness in controlling blood pressure among South Asian patients. The TOPSPIN (Treatment Optimisation of blood Pressure with Single-Pill combinations in INdia) trial, published in Nature Medicine, represents the first robust comparison of dual antihypertensive combinations specifically in South Asian populations.
Study Design and Participants
The multicenter trial enrolled 1,981 participants aged 30-79 years across 32 hospitals throughout India, comparing three dual combination therapies: amlodipine plus perindopril, amlodipine plus indapamide, and perindopril plus indapamide. All medications were administered as single-pill combinations to improve patient adherence.
Participants had uncontrolled hypertension, with sitting office systolic blood pressure between 140-159 mmHg on one antihypertensive medication or 150-179 mmHg in treatment-naive patients. The study population had a mean age of 52.1 years, with 42.1% women and 18.6% having self-reported diabetes.
Primary Efficacy Results
After six months of treatment, all three combinations demonstrated substantial and statistically equivalent reductions in 24-hour ambulatory blood pressure measurements. The unadjusted reductions in systolic blood pressure were 14.5 mmHg for amlodipine-perindopril, 13.3 mmHg for perindopril-indapamide, and 13.9 mmHg for amlodipine-indapamide.
"All three combinations worked equally well in reducing blood pressure and were safe for patients," the study revealed. Office blood pressure measurements showed even more dramatic improvements, with reductions of approximately 30/14 mmHg across all treatment groups.
Clinical Control Rates
The trial achieved remarkable blood pressure control rates that substantially exceed current national averages. Nearly 70% of participants achieved conservative blood pressure control targets (below 140/90 mmHg), while over 40% reached more stringent current targets (below 130/80 mmHg).
Dr. Ambuj Roy, Professor of Cardiology at AIIMS Delhi, emphasized the clinical significance: "Nearly 70 per cent of patients got their blood pressure under control, a huge improvement over the current national average. And the pills were safe and easy to use. This study gives clear guidance for better hypertension care."
Safety Profile
All three combinations demonstrated excellent safety profiles. Only 51 participants (2.6%) experienced adverse events requiring withdrawal of study medication, with dizziness (23 participants), pedal swelling (12 participants), and headache (10 participants) being the most commonly reported side effects.
Serious adverse events occurred in 21 participants, but none were attributed to the study drugs. Two-thirds of participants maintained good adherence throughout the trial, consuming 80% or more of prescribed medications.
Laboratory and Metabolic Effects
The study revealed several clinically relevant differences in laboratory parameters between treatment groups. The amlodipine-perindopril combination showed significant improvements in fasting blood glucose and glycated hemoglobin levels compared to amlodipine-indapamide, which may have important implications for South Asian populations with high diabetes propensity.
Hypokalemia occurred in 7.4% of participants overall, with differential effects across groups. The amlodipine-indapamide combination showed the highest rate at 15.2%, highlighting the need for routine electrolyte monitoring, particularly with diuretic-containing regimens.
Clinical Implications for South Asian Populations
The findings address a critical knowledge gap in hypertension management for South Asian populations, who constitute a quarter of the world's population. India faces an enormous hypertension burden with an estimated 300 million individuals affected, yet poor blood pressure control rates of only 7-11% in rural areas and 11-20% in urban populations.
The study results contrast with the CREOLE trial conducted in sub-Saharan Africa, where calcium channel blocker combinations showed superior efficacy. This highlights the importance of population-specific evidence in guiding treatment decisions.
Study Strengths and Limitations
The trial's strengths include its large sample size, multicenter design across diverse Indian populations, and use of gold-standard 24-hour ambulatory blood pressure monitoring. The three drug components have established cardiovascular outcome benefits from previous trials, providing additional confidence in their clinical utility.
Limitations include the 17.4% of participants who did not complete 24-hour ambulatory recordings at six months, though sensitivity analyses confirmed the robustness of findings. The study also did not evaluate all possible two-drug combinations or assess long-term cardiovascular outcomes.
The research provides novel evidence supporting the use of any of the three evaluated dual combinations for hypertension treatment in South Asian populations, with implications extending beyond India to the broader South Asian diaspora worldwide.
