Hypertension Fixed-Dose Quadpill Treatment Linked to Decrease in Blood Pressure


Investigators observed systolic blood pressure was lower by a rate of 6.9 mm Hg in the intervention group versus the control group.

Clara K Chow, PhD

Clara K Chow, PhD

Finding new, effective treatment strategies may decrease treatment inertia, a known barrier to blood pressure control in patients with hypertension.

A new study, presented at the European Society of Cardiology (ESC) 2021 Congress, aimed to determine if a single pill with ultra-low-dose quadruple combination therapy was more effective than a monotherapy starting strategy.

Investigators, led by Clara K Chow, PhD, Westmead Applied Research Centre, Faculty of Medicine and Health, University of Sydney, found an earlier treatment strategy of a fixed-dose quadruple quarter-dose combination achieved great blood pressure lowering in comparison with a monotherapy strategy.


The team performed the Quadruple Ultra-low-dose Treatment for Hypertension (QUARTET), a multi-center, randomized, phase 3 trial of Australian adults (≥18 years) with hypertension. Patients were either untreated or receiving monotherapy.

They were randomly assigned to either treatment of the “quadpill”, including irbesartan at 37.5 mg, amlodipine at 1.25 mg, indapamide at 0.625 mg, and bisoprolol at 2.5 mg, or a monotherapy control of irbesartan 150 mg. Additional medications could be used if blood pressure did not meet target, beginning with amlodipine at 5 mg.

Primary outcomes included the difference in unattended office systolic blood pressure at 12 weeks, with secondary outcomes including blood pressure control, safety, and tolerability. They noted standard office blood pressure at <140/90 mm Hg.


A total of 743 patients were screened for eligibility from June 2017 - August 2020, with 591 participants included in the study.

Of the 591 participants, 300 were randomized to the intervention of initial quadpill treatment and 291 were randomized to control of initial standard dose monotherapy treatment.

Data show a mean age of 59 years, with 356 male participants (60%) and 235 female participants (40%). In addition, 483 (82%) were White, 70 (12%) were Asian, and 38 (6%) reported as other ethnicity. The baseline mean unattended office blood pressure was 141 mm Hg/85 mm Hg.

At 12 weeks of the study, 44 participants (15%) in the intervention group had additional blood pressure medication, compared to 115 participants (40%) in the control group.

In addition, investigators observed systolic blood pressure was lower by a rate of 6.9 mm Hg (95% CI, 4.9 - 8.9, P <.0001) in the intervention group versus the control group.

They also found blood pressure control rates were higher in the intervention group (76%) versus the control group (58%; relative risk RR 1.30; 95% CI, 1.15 - 1.47, P <.0001).

The team saw no difference in adverse event-related treatment withdrawal at 12 weeks in the intervention group (4.0%) compared to control (2.4%; P = .27). In the patients who continued treatment (n = 417), it was shown that uptitration occurred more frequently in the control group compared to the intervention group (P <.0001).

Then, at 52 weeks, the mean unattended systolic blood pressure was lower by 7.7 mm Hg (95% CI, 5.2 - 10.3) and blood pressure control rates higher in the intervention group (81%), in comparison to the control group (62%; RR 1.32, 95% CI, 1.16 - 1.50).

A total of 7 serious adverse events (3%) were observed in the intervention group and 3 adverse events (1%) in the control group.


“A strategy with early treatment of a fixed-dose quadruple quarter-dose combination achieved and maintained greater blood pressure lowering compared with the common strategy of starting monotherapy,” investigators wrote. “This trial demonstrated the efficacy, tolerability, and simplicity of a quadpill-based strategy.”

The study, “Initial treatment with a single pill containing quadruple combination of quarter doses of blood pressure medicines versus standard dose monotherapy in patients with hypertension (QUARTET): a phase 3, randomised, double-blind, active-controlled trial,” was published online in The Lancet.

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