Three dual combinations of commonly prescribed antihypertensives ? amlodipine and perindopril, perindopril and indapamide, or amlodipine and indapamide ? demonstrated equal blood pressure (BP)-lowering efficacy among Indian adults, according to the results of the TOPSPIN trial presented at AHA 2024.

Current hypertension guidelines suggest combining BP-lowering agents, but it remains unclear which drug combos have the potential to offer the best outcomes among South Asians.

“South Asians account for a quarter of the world’s population, and India, in particular, has an enormous burden of hypertension, leading to high stroke and cardiovascular disease risk,” said lead investigator Dr Dorairaj Prabhakaran from the Centre for Chronic Disease Control, New Delhi, India. “Optimal BP management is essential to lower the cardiovascular complications of high BP.”

TOPSPIN was specifically initiated to ascertain the best dual combination for hypertension management in individuals of South Asian descent. This multicentre, single-blind, three-arm trial evaluated 1,981 participants (median age 52 years, 58 percent men) who had sitting office systolic BP of 140?159 mm Hg on one antihypertensive drug or 150?179 mm Hg on no treatment.

Participants were randomized 1:1:1 to receive one of three daily single-pill combos at starting doses of either amlodipine (calcium channel blocker) and perindopril (angiotensin-converting enzyme inhibitor), perindopril and indapamide (diuretic), or amlodipine and indapamide. Initial doses were force titrated to full doses at 2 months unless the systolic BP was <120 mm Hg.

Over half of the participants were taking at least one antihypertensive at enrolment. About 19 percent had type 2 diabetes and 6.2 percent were current smokers. Ambulatory BP was measured at enrolment and at 2, 4, and 6 months. [AHA 2024, abstract 4166995]

At 6 months, all three drug combos lowered BP equally. The mean change in the primary endpoint of 24-hour ambulatory systolic BP was similar with amlodipine and perindopril (?14.5 mm Hg), amlodipine and indapamide (?13.9 mm Hg), and perindopril and indapamide (?13.3 mm Hg). When measured in a clinic, the mean reduction in systolic BP was about 30 mm Hg.

About three-quarters of participants were able to get their BP under 140/90 mm Hg, and over 40 percent achieved the stricter BP target of 130/80 mm Hg.

All three drug combos had an excellent safety and tolerability profile, with only 2.6 percent of participants reporting treatment discontinuation due to adverse effects. Reductions in fasting blood sugar levels after 6 months were reported in the amlodipine-perindopril group.

“It was reassuring to find that all three dual combinations of commonly recommended [BP] medications were equally effective,” said Prabhakaran. He added that the results counter those observed in the CREOLE trial, which found amlodipine-based combinations to be superior to two other dual combination regimens in Black adults with hypertension in Sub-Saharan Africa.

Major clinical implications

“TOPSPIN is the first randomized evaluation of commonly used combination therapies in a South Asian population,” noted Prabhakaran and colleagues. Although almost 20 percent of participants did not complete the trial, the findings may have major clinical implications for improving BP control, they added.

“The results of this study can be easily extrapolated to larger populations due to the diversity of the participants enrolled in India and the South Asian diaspora at large … More than 5 million South Asian people live in the US, so these findings have huge relevance for them,” said Prabhakaran.