VIDEO: Triple-antihypertensive pill nails early therapy

By Mitchel L. Zoler  Cardiology News

REPORTING FROM ACC 18

ORLANDO – Hypertensive adults started on a triple-drug, single daily pill regimen as either initial or early treatment had a sharply better rate of reaching their goal blood pressure after 6 months, compared with usual-care controls, in a multicenter, randomized trial with 700 patients.

“Early use of a low-dose, three-in-one blood pressure lowering pill is safe and provides faster and better control of blood pressure compared with usual care,” Ruth Webster, PhD, said at the annual meeting of the American College of Cardiology.

The tested polypill contained half the standard doses of the angiotensin receptor blocker telmisartan (20 mg), the calcium channel blocker amlodipine (2.5 mg), and the diuretic chlorthalidone (12.5 mg). After 6 months on this regimen, 70% of patients were at their goal blood pressure, compared with 55% of the control patients, and patients on the polypill had on average a 10/5 mm Hg greater reduction in their blood pressure than did patients on usual care, reported Dr. Webster, head of research programs at the George Institute for Global Health in Sydney. Rates of total and serious adverse events and withdrawals because of adverse events were similar in the two study arms, and both arms also had nearly identical levels of treatment adherence, about 95%.

“No prior trial has evaluated a triple, low-dose pill for initial or early treatment,” she noted.

“This is a home run,” said Karol E. Watson, MD, professor of medicine and director of the Women’s Cardiovascular Health Center at the University of California, Los Angeles. “In the past, clinicians were told to pick one drug and push it as hard as you could and then maybe think about adding a second drug. Experience has shown that this does not increase efficacy, but it does increase adverse events, so current guidelines say start with two drugs. Now they are showing for the first time that you should start with three drugs. That goes with what we know.”

“Triple-drug therapy for the masses makes complete sense,” especially now that the blood pressure goal for most patients is less than 130/80 mm Hg, said William B. White, MD, professor of medicine and chief of hypertension and clinical pharmacology at the University of Connecticut in Farmington. Plus, “compliance is vastly improved when you use a combination-drug pill,” he noted.

The blood pressure targets that Dr. Webster and her associates used were less than 140/90 mm Hg except in patients with diabetes or chronic kidney disease, who had a target of less than 130/80 mm Hg. At the time researchers designed the trial the generally accepted blood pressure target for antihypertensive treatment was less than 140/90 mm Hg, Dr. Webster noted.

She also stressed that she did not believe the three specific drugs selected for the polypill made a difference. “The specific drugs we used was not that important. We would probably get the same result with different drugs. It’s about the strategy of using triple, low-dose therapy,” Dr. Webster suggested. Dr. Watson agreed.

The TRIUMPH (Triple Pill vs. Usual Care Management for Patients with Mild to Moderate Hypertension) study enrolled patients at 11 hospital outpatient clinics in Sri Lanka. The average age of the patients was 56 years. The average blood pressure was 154/90 mm Hg. About 59% of patients were not on any antihypertensive drug at baseline, with the rest on a single drug. The study protocol excluded patients on two or more drugs at entry. Roughly 30% of enrolled patients had diabetes, and 1%-2% had chronic kidney disease. Their target blood pressure on treatment during the study was less than 130/80 mm Hg.

The study’s primary endpoint was the percentage of patients at their goal blood pressure after 6 months. Patients in the triple-drug polypill group achieved their goal blood pressure 23% more often relative to the control, usual care patients, a statistically significant difference. The between group difference in achievement of goal blood pressure was apparent by the end of the first 6 weeks in the study. Patients in the control arm generally received either one or two drugs during the study, but often at full dose rather than the half doses used in the triple-drug patients. The study’s design specified that patients in the triple-drug arm who were not at their target blood pressure after 6 weeks could, at the discretion of their treating physician, switch to a second formulation that doubled the dosage of each of the three drugs. Patients in the usual care arm could have their treatment adjusted after 6 or 12 weeks as long as they continued to receive either one or two drugs. After 6 weeks, 68% of patients in the triple-drug arm and 44% receiving usual care were at their blood pressure goal. After 12 weeks, the percentages at goal were 73% of patients on the triple-drug pill and 47% on usual care.

Dr. Webster hypothesized that the triple-drug, low-dose strategy for initial or early treatment would surpass usual care not only in low- and middle-income countries, like Sri Lanka, but also in high-income, industrialized countries such as the United States.

TRIUMPH received no commercial funding. Dr. Webster had no disclosures. Dr. Watson has been a consultant to Amgen, AstraZeneca, Boehringer Ingelheim, Daiichi Sankyo, and GlaxoSmithKline. Dr. White has been a consultant to Novartis.

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SOURCE: Webster R. ACC 2018. Webster R et al. ACC 18 late breaker.