Dual-medication polypills effectively lowered blood pressure among South Asian adults
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Key takeaways:
- Three polypills, each containing two antihypertensive drugs, effectively lowered blood pressure for Indian adults with hypertension.
- There were no between-group differences in all measurements of BP lowering.
CHICAGO — Among adults living in India with elevated BP, three different dual-medication polypills containing combinations of recommended first-line antihypertensive agents effectively lowered ambulatory BP, researchers reported.
Data from TOPSPIN, a randomized, three-arm trial of single-pill combinations of a renin-angiotensin system inhibitor, a long-acting ACE inhibitor and a thiazide-type diuretic, also demonstrated that the three combinations were equally effective across groups in a South Asian population, where there remains an outsize hypertension burden.
“There is no advantage of one combination above the others,” Dorairaj Prabhakaran, MD, DM, MSc, executive director of the Centre for Chronic Disease Control in New Delhi, told Healio during a press conference at the American Heart Association Scientific Sessions. “All three combinations worked very well and mean office BP reduction was 30/15 mm Hg. We leave the choice to the physicians who treat these patients. Cost [between choices] may be a factor, but that is also not huge and cost is fairly similar among the three.”
Adults with poorly controlled hypertension
Researchers analyzed data from 1,981 adults from 35 clinics across India with a systolic BP of 140 mm Hg to 160 mm Hg on one antihypertensive agent or a systolic BP of 150 mm Hg to 180 mm Hg with no antihypertensive treatment. The mean age of participants was 52 years; 42% were women and 55% were already taking BP-lowering medications. Participants were free of CVD at baseline; however, 18.6% reported a diabetes diagnosis and 6.2% were smokers.
Researchers randomly assigned participants to a single-pill combination of starting doses of amlodipine and perindopril, perindopril and indapamide, or amlodipine and indapamide. Study investigators force titrated to full doses at 2 months unless the systolic BP was lower than 120 mm Hg.
Primary outcome was 24-hour ambulatory systolic BP at 6 months. Secondary endpoints included ambulatory diastolic BP, daytime and nighttime BP and 24-hour BP variability, clinic BP at 2, 4 and 6 months, the proportion of participants achieving BP control and safety endpoints.
At 6 months, participants in all three combination pill groups experienced on average a 14 mm Hg reduction in ambulatory systolic BP, with no between-group differences. Mean office BP fell by 30/14 mm Hg, again with no between-group differences observed. In all three polypill groups, more than 40% of participants achieved a BP of lower than 130/80 mm Hg and more than 70% achieved a BP of less than 140/90 mm Hg.
Prabhakaran noted that there were significant but clinically minor differences in renal function, potassium and uric acid across the three groups and that 51 participants withdrew from the study citing adverse events that are commonly associated with the individual drug classes.
Improving medication adherence
In a discussant presentation of the TOPSPIN findings, Shawna Nesbitt, MD, MS, professor of internal medicine and cardiology and chief institutional opportunity officer at UT Southwestern Medical Center, said an ideal, fixed-combination BP therapy would need to have several characteristics, including high efficacy, synergy between the two agents, data from large trials, mitigation of adverse effects, potential for wide availability and affordability, safety and a daily dosing formulation.
“This trial represents three drugs that fit all of these characteristics very well,” Nesbitt said.
Nesbitt noted that findings are particularly useful as the 30-year increase in adults with hypertension rose 144% in the South Asia and Western Pacific region, with very few patients well controlled.
“Patients treated with combination therapy are more likely to be adherent to therapy and more likely to be persistent with therapy at 1 year and are more likely to refill their prescription than those who are taking separate agents not in a single pill,” Nesbitt said. “This is important because an issue we face in treating hypertension is many patients frequently stop taking their medications or they stop taking more than one of them because of cost or other issues.”
Perspective
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Keith C. Ferdinand, MD, FACC, FAHA, FASPC, FNLA
One of the interesting things about this study is the investigators used already approved and already effective BP medications, but in combinations to see which of those combinations would be most beneficial for BP reduction. It included a renin-angiotensin-aldosterone system blocking agent, perindopril, a long-acting ACE inhibitor, a thiazide-type diuretic, indapamide, and then a long-acting calcium channel blocker (CCB), amlodipine, already shown to be effective across a wide range of populations. The question asked was which of these combinations would be most efficacious for BP reduction. The answer appears to be that all are equally efficacious.
This is in line with emerging consensus across hypertension specialists, both here in the U.S., in Europe and increasingly in other countries, that treating high BP is not going to be about which medication is best. Instead, the question will be which combination is best? Combination therapy will be the first step for stage 2 hypertension, which many of the people in this South Asian cohort have.
I look further for some delineation of the thiazide-type diuretic and CCB combination because the investigators mentioned some differences in metabolism. We know that adding a CCB to an ACE inhibitor will not have a deleterious effect on glucose, potassium and uric acid. In fact, it may protect against some of the metabolic derangements that we may see with more potent thiazide-type diuretics. I would like to see data on any changes in levels of potassium, uric acid, sodium and glucose with the CCB/thiazide-type combination.
We also want to know, especially in developing societies, if we will be able to apply medicines more broadly without perhaps some of the close monitoring you would see in urban areas or more developed societies. Overall, the message is, for people with stage 2 and above hypertension, regardless of where they reside in the world, it is crucial to start combination therapy using effective long-acting agents.
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Prabhakaran D, et al. LBS.05. Presented at: American Heart Association Scientific Sessions; Nov. 16-18, 2024; Chicago.
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