New Delhi: A clinical trial has found that dual combinations of hypertension drugs are more effective in reducing blood pressure (BP) than individual medicines, prompting top cardiologists and researchers to recommend bringing these fixed-dose combinations (FDCs) under price control.
The first such trial, named TOPSPIN and spearheaded by the New Delhi-based Centre for Chronic Disease Control (CCDC), tested the efficacy of three dual-drug combinations—amlodipine and perindopril, amlodipine and indapamide, and perindopril and indapamide.
CCDC is a collaboration between the World Health Organization (WHO) and the Indian Council of Medical Research (ICMR).
All three combinations were found to be nearly 70 percent more effective in achieving BP control compared to single pills, according to results from the randomised clinical trial led by the All India Institute of Medical Sciences (AIIMS) in New Delhi.
The results of the study, conducted across 32 hospitals in the country, were published in the peer-reviewed journal Nature Medicine last week.
Currently, only one of the three drugs used in the trials, amlodipine, is a scheduled drug in India. This means it is included in the National List of Essential Medicines (NLEM) and its upper ceiling price is regulated by the government every year.
But CCDC Executive Director Dr Dorairaj Prabhakaran, one of the principal investigators, said the drug combinations should be part of the NLEM as they can reduce costs and improve adherence to prescribed medicines. “The move will ensure availability (of these drugs) at the primary care level, which treats more than 50 percent of the population to improve blood pressure control in India,” said Prabhakaran.
Hypertension, or high BP, occurs when the pressure in the blood vessels is too high—140/90 mm HG (millimetres of mercury) or higher. The first number, known as systolic pressure, measures pressure created as blood pumps out of the heart and into the arteries, while the diastolic pressure is the pressure created as the heart rests between heartbeats.
A 2023 large study by the Indian Council of Medical Research (ICMR) and the Madras Diabetes Research Foundation (MDRF), showed that India has 31.5 crore people with hypertension. But it is estimated that fewer than 10 percent of people with hypertension had their blood sugar under control in 2019-21.
If left untreated for long, the condition, called a ‘silent killer’, could lead to serious health complications, including heart attack, stroke, kidney disease and vision loss.
Initiating dual combinations of BP-lowering therapy, ideally as single-pill combinations (SPCs), is one of the proposed mechanisms for improving BP management, the researchers said.
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Why India needs to shift to hypertension FDCs
According to recent guidelines, diagnosis of hypertension typically requires at least two BP-lowering medications, as monotherapy effectively achieves optimal BP control for only about 30 percent of patients.
Current recommendations advocate combination therapy as a first-line treatment in most adults, particularly patients with comorbid conditions that require rapid BP reduction.
These combinations usually include an angiotensin-converting enzyme (ACE) inhibitor such as perindopril, which relaxes blood vessels; or an angiotensin II receptor blocker (ARB) paired with a calcium channel blocker (CCB) such as amlodipine, which prevents calcium from entering the heart’s muscle cells and blood vessels, thereby relaxing them; or a thiazide or thiazide-like diuretic like indapamide, which treats hypertension by increasing the excretion of water and salt from the body.
Based on this, 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 have ever been conducted in India, nor have enough South Asians been included in international trials.
South Asians represent one-fourth of the world population, with India alone accounting for one-sixth of the global population, the researchers said. They added that more innovative solutions are needed to curb the growing tide of cardiovascular disease and high blood pressure, the single highest risk factor for global deaths, which requires effective management solutions.
Two-drug combination therapies ideally delivered in a single pill are widely recommended to improve blood pressure control, but which combinations are suitable for the South-Asian population was previously unknown.
The trial results, involving 1,981 Indian patients between 2022-24, however, demonstrated that all three combinations are equally effective and safe in reducing ambulatory blood pressure monitored over 24 hours and office blood pressure randomly checked at a doctor’s office.
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 smokers.
After six months, all three combinations lowered BP equally, roughly 14/8 mm Hg on 24-hour ambulatory BP monitors and 30/14 mm Hg 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 combination pills, with fewer than three percent of all study participants ending treatment due to adverse effects.
Additionally, participants in the amlodipine-perindopril combination group also experienced a decrease in fasting blood sugar levels after six months.
‘Price control will expand access’
The results have prompted researchers to recommend that India expand its NLEM to include these specific hypertension FDCs.
The latest version of the NLEM, released in 2022, has 384 drugs and over 1,000 formulations across 27 therapeutic categories, but includes very few such combinations.
FDCs combine two or more drugs in a single pharmaceutical form, such as a capsule.
While the price of 2.5 mg, 5 mg and 10 mg amlodipine has been fixed at Rs 1.79, Rs 2.5 and Rs 5.45 per tablet, FDC tablets containing amlodipine and perindopril are not under price control and can cost Rs 17- 27 per tablet, depending on the manufacturer.
“Bringing these specific hypertension FDCs under NLEM will make them accessible to a high number of Indians and will even lead to government initiatives managing the condition in a cost-effective way,” Dr Ambuj Roy, senior interventional cardiologist with AIIMS, and a principal investigator of the research project, told ThePrint.
Scheduled drugs, included in the NLEM, are mostly made available free of cost to patients through government hospitals as part of various health programmes at the primary, secondary and tertiary levels of healthcare.
(Edited by Sugita Katyal)
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