3 days Ago By Sumi Sukanya Dutta
New Delhi: The findings from a crucial clinical trial that may transform hypertension management in India have shown that two-drug combinations of three widely used medicines used in patients with high blood pressure (BP) are far more effective in controlling the condition than single medicines. The clinical trial was spearheaded by the Centre for Chronic Disease Control (CCDC), a collaboration between the World Health Organisation and the Indian Council of Medical Research (ICMR), and led by the All India Institute of Medical Sciences (AIIMS), Delhi, across 35 hospitals, both government and private, across the country. The trial, named TOPSPIN and sponsored by Imperial College, London, tested the efficacy of three two-drug combinations—amlodipine and perindopril, amlodipine and indapamide, and perindopril and indapamide.
It revealed that all three combinations achieved BP control in roughly 70 percent of patients undergoing trial, that is, was five times more effective than a single drug. The results have demonstrated that all three combinations are equally effective and safe in reducing ambulatory blood pressure, that is, BP monitored over 24 hours, and office blood pressure, that is, BP randomly checked at a doctor’s office. Amlodipine is available under brand names such as Amlong, Amlovas, Amlosafe and others; perindopril is available as Perigard, Gatosyl and Coversyl; and indapamide is available as Natrilix, Lorvax and Divret.
Hypertension or high BP is when the pressure in the blood vessels is too high—140/90 mm HG (millimetres of mercury) or higher—represented by a combination of systolic and diastolic pressures. The systolic pressure is the pressure created as blood pumps out of the heart and into the arteries, and the diastolic pressure is the pressure created as the heart rests between heartbeats. The results from the multi-centre, randomised clinical trial—carried out in 1,981 Indian patients between 2022-24—were presented at the 2024 scientific sessions of the American Heart Association in Chicago Sunday.
Hypertension is a significant cause of mortality and disability in India, affecting nearly 30 percent of the population. The rates of controlling hypertension are low, standing at a dismal 11 percent in rural areas and 20 percent in urban areas, according to the ICMR. Experts say that lowering blood pressure to target levels is crucial for preventing cardiovascular issues in hypertensive patients, with multiple medications often required to achieve this goal.
However, there has been a lack of specific trial data on the most effective combinations of antihypertensive drugs for patients of South Asian origin. Current drug selection guidelines in India primarily hinge on international standards, which might not fully apply to Indian patients. “With the latest evidence, healthcare professionals can be better equipped to recommend any of these three combination therapies in managing hypertension among South Asians,” said Dr Dorairaj Prabhakaran, the executive director of CCDC and one of the study’s principal investigators.
Also Read: India had highest number of diabetics in the world in 2022, 62% were not on medication—Lancet report The “Global report on hypertension: The race against a silent killer”, which the WHO released last year, said that at least 188.3 million people aged 30-79 years in India live with the condition. It also said that only 37 percent of Indians are diagnosed with the condition, a leading cause of death and disability, in time and even fewer, just roughly 30 percent, get treatment.
According to recent guidelines, this typically necessitates using at least two BP-lowering medications, whereas monotherapy effectively achieves optimal BP control for only approximately 30 percent of patients. Current recommendations advocate the initiation of combination therapy as a first-line treatment in most adults, particularly in patients with comorbid conditions necessitating rapid BP reduction. These combinations usually include an angiotensin-converting enzyme (ACE) inhibitor, such as perindopril, relaxing blood vessels; an angiotensin II receptor blocker (ARB) paired with a calcium channel blocker (CCB), such as amlodipine, preventing calcium from entering the muscle cells of the heart and blood vessels and relaxing them; and a thiazide or thiazide-like diuretic, such as indapamide, treating hypertension by increasing the excretion of water and salt from the body.
Similarly, the latest Indian hypertension guidelines endorse the use of low doses of drug combinations to achieve the desired BP control. However, no trials on the optimal initial antihypertensive combination had earlier been done in India, nor had enough South Asian individuals been part of the international trials. As a result, Indian guidelines on antihypertensive drug selection and sequencing were extrapolated primarily from international guidelines, which may or may not apply to the Indian patient population, according to researchers.
Also Read: Top panel suggests bringing health supplements under drug laws, greater scrutiny of their claims As part of the TOPSPIN trial, the researchers randomised 1,981 adults with high BP—aged 30 to 79 (median age 52)—at 35 hospitals in India to receive a single pill that included either amlodipine and perindopril, perindopril and indapamide, or amlodipine and indapamide. Of the patients, 42 were women. Ambulatory BP was measured—at enrolment first and, subsequently, at two, four and six months.
At the time of enrolment, 55 percent of the participants were already taking some BP-lowering medication, 18.6 percent had type 2 diabetes, and 6.2 percent were current smokers.
After six months, results showed that all three combinations of the medications lowered BP equally, roughly 14/8 mm Hg lower when measured using 24-hour ambulatory BP monitors and 30/14 mm Hg lower when measured in a clinic. The study achieved blood pressure control in approximately 70 percent of participants to less than 140/90 mm Hg—five times the current BP control rates in India with just a single drug. Also, a stricter BP target, 130/80 mmHg, was achieved in 40 percent of the study participants.
The researchers also noted an excellent safety profile of each of the three combinations, with fewer than three percent of all study participants ending treatment due to adverse effects from the medications. Additionally, participants in the amlodipine-perindopril combination group also experienced a decrease in fasting blood sugar levels after six months. Dr Ambuj Roy, a professor at the AIIMS cardiology department and another of the study’s principal investigators, said the study bridges a critical knowledge gap in hypertension treatment for South Asians.
“Even now,” Roy told ThePrint, “cardiologists prescribe these drug combinations to patients, but there was no evidence from our population regarding which combinations work best and are the safest.” “The results provide novel evidence to choose any of these three combinations to treat high blood pressure in Indians. It is important to note that the blood pressure control achieved with a single pill a day in 70 percent of the participants in the study exceeded the current control rates in India by 5 times,” he said.
The cardiologist added that this has important implications for the management of hypertension, a public health burden in India. A surprising outcome of the study was the lack of significant difference in BP control between the combinations tested—which contrasts with findings from the CREOLE study conducted in Sub-Saharan Africa. The findings, when looked at together, suggest that the combination therapies tested may have different effectiveness by ethnicity, the CCDC said.
Dr Neil Poulter, professor of preventive cardiovascular medicine at Imperial College, London, said the results of the study in India will play a crucial role in shaping the future of hypertension management not only in the country but also across the South-Asian diaspora. “These findings can guide physicians in selecting the most effective treatment strategies for patients, ensuring better blood pressure control with minimal risk,” he said. (Edited by Madhurita Goswami) Also Read: Killer superbugs mainly emerging from hospitals, not animals & environment—study by Indian, UK scientists Save my name, email, and website in this browser for the next time I comment.
Δ document.getElementById( "ak_js_1" ).setAttribute( "value", ( new Date() ).
getTime() );.
