‘Quad therapy’ strategy may improve BP control vs. angiotensin receptor blocker monotherapy
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CHICAGO — An ultra-low-dose four-drug quad therapy may improve BP control among patients with hypertension, with no increased safety risk, compared with angiotensin receptor blocker monotherapy, according to a small, first-in-U.S. study.
The results of the Quadruple Ultra-low-dose Treatment for Hypertension (QUARTET-USA) study were presented at the American Heart Association Scientific Sessions.
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“Replacing individual monotherapy with a four-drug, quarter-dose blood pressure-lowering combination led to a 4.8/4.9 mm Hg greater reduction in change in blood pressure from baseline to 12 weeks compared with standard-dose [angiotensin receptor blocker] monotherapy in patients with mild to moderate hypertension. That’s even with 53% uptitration in the control group,” Mark D. Huffman, MD, MPH, adjunct professor of preventive medicine at Northwestern University Feinberg School of Medicine, said during a presentation. “The differences in systolic blood pressure were not statistically significant, which is likely due to limited power related to sample size. Adverse events were more common in the intervention group, but the rate of discontinuation was higher in the comparator group. No serious adverse events were related to the study drug.”
As Healio previously reported, in the original QUARTET trial of 591 patients from Australia, the quad therapy strategy conferred greater BP reductions compared with monotherapy, with similar safety and tolerability and despite uptitration of therapy in the monotherapy arm.
QUARTET-USA was a randomized controlled trial that enrolled 62 patients (mean age, 52 years) in the Access Community Health Network in Chicago who were treatment-naive and had systolic BP 140 mm Hg to 179 mm Hg/diastolic BP 90 mm Hg to 109 mm Hg or who were already on monotherapy and had systolic BP 130 mm Hg to 159 mm Hg/diastolic BP 85 mm Hg to 99 mm Hg. Patients were assigned to the quad therapy, which consisted of a single pill (“polypill”) combination therapy of candesartan 2 mg, amlodipine 1.25 mg, indapamide 0.625 mg and bisoprolol 2.5, or to a comparator of candesartan 8 mg daily. The on-treatment period lasted 12 weeks and the primary outcome was mean change in automated systolic BP. The key secondary outcome was mean change in diastolic BP.
In both groups, if BP remained greater than 130/80 mm Hg at 6 weeks, an add-on of amlodipine 5 mg daily was given.
Approximately three-quarters of the study population was Hispanic and more than half of the cohort had annual household income less than $25,000.
Add-on amlodipine was prescribed in 18.8% of the quad therapy arm and 53.3% of the comparator group.
In the quad therapy group, the adjusted mean change in systolic BP at 12 weeks was –4.8 mm Hg (95% CI, –10.7 to 1.2) and the mean change in diastolic BP was –4.9 mm Hg (95% CI, –8.6 to –1.1) compared with monotherapy.
Researchers observed numerically more adverse events in the quad therapy arm than the comparator arm, and the two serious adverse events in the quad therapy arm were determined to be unrelated to the treatment regimen.
“New approaches are urgently needed to achieve lower blood pressure targets, especially for patients and communities with a high burden of hypertension and hypertension-related diseases,” Huffman said during the presentation. “QUARTET-USA was the first trial of a four-drug, ultra-low-dose blood pressure-lowering combination therapy in the United States. The direction and magnitude of blood pressure-lowering effect were similar between QUARTET in Australia and QUARTET-USA, despite being different study populations with lower baseline blood pressure in the current study, thus strengthening the case for this new approach.”
Editor’s Note: This article was updated on November 18, 2022 to correct some of the description of the trial’s methods. The Editors regret the error.
References:
- Baldridge AS, et al. Am Heart J. 2022;doi:10.1016/j.ahj.2022.09.004.
- Chow CK, et al. Lancet. 2021;doi:10.1016/S0140-6736(21)01922-X.
Perspective
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Keith C. Ferdinand, MD, FACC, FAHA, FASPC, FNLA
The polypill is not a bad concept. Simplifying pill burden may increase adherence, since most middle-aged and older people need two or more medicines to control BP.
The ultra-low-dose quadruple-combination pill vs. standard-dose monotherapy did not quite reach statistical significance for systolic BP at 12 weeks, but did show a trend toward BP reduction.
If clinicians can combine BP medications, going from four or five pills to two or three pills, it may increase adherence, which is a big problem in the hypertension population. One reason for persistent suboptimal BP control is that only about 50% of patients with hypertension are adherent after 2 years.
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Huffman M, et al. LBS.04: Mindful Disruption of Chronic Hypertension Management. Presented at: American Heart Association Scientific Sessions; Nov. 5-7, 2022; Chicago (hybrid meeting).
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