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Randomized Controlled Trial
. 2025 Dec 18;12(2):e003843.
doi: 10.1136/openhrt-2025-003843.

Pooled randomised QUARTET trials assessing effectiveness of a single pill for hypertension

Simone Marschner  1 , Mark D Huffman  2   3 , Desi Quintans  4 , Jody Ciolino  5   6 , Abigail Baldridge  7 , Danielle Lazar  8 , Emily R Atkins  9   10 , Graham S Hillis  11 , Mark R Nelson  12 , Markus Schlaich  13   14 , Anthony Rodgers  15 , Clara K Chow  16
Affiliations
Randomized Controlled Trial

Pooled randomised QUARTET trials assessing effectiveness of a single pill for hypertension

Simone Marschner et al. Open Heart. .

Abstract

Background: Hypertension is a major cause of premature death worldwide, controlled by only one in five adults. Two trials (Australia and USA) found a single quadpill containing a quarter dosage of four classes of medication effective in reducing blood pressure (BP) among participants with hypertension. By pooling these trials, we can estimate the overall benefit of the quadpill and its heterogeneity across subgroups and two important barriers for BP control: clinician medication inertia and participant medication adherence.

Methods: In a prespecified pooled individual participant data analysis of two QUARTET randomised, multicentre, double-blinded trials in people with hypertension using ≤1medication, quadpill (irbesartan (37.5 mg) (Australia)/candesartan (2 mg) (USA)), amlodipine (1.25 mg), indapamide (0.625 mg), bisoprolol (2.5 mg) unattended office systolic BP (SBP) at 12 weeks was compared with initial monotherapy (irbesartan (150 mg) (Australia), candesartan (8 mg) (USA)). Heterogeneity was assessed using an interaction term in the mixed cox model. Adherence, ≥80% pill count and treatment inertia were estimated.

Results: In 653 participants (Australia, 591 (91%); USA, 62 (9%)) a significant drop in mean SBP (6.5 mm Hg (95% CI 4.8 to 8.8; p<0·001)) and diastolic BP (5.6 mm Hg (95% CI 4.5 to 6.9; p<0.001)) in favour of the quadpill was found, with less need for uptitration (p<0.001) and less treatment inertia (non-significant: p=0.303). Adherence was high for both treatment arms (over 80%). Compared with monotherapy, the quadpill effect varied by ethnicity (SBP reduced by White (6.9 mm Hg; 95% CI 4.7 to 9.2), Hispanic (3.3 mm Hg; 95% CI 4.0 to 10.6), Asian (12.3 mm Hg; 95% CI 6.2 to 18.5) and Black/other (1.4 mm Hg; 95% CI -9.0 to 6.3), interaction p=0.032).

Conclusion: This prospective individual participant data pooled analysis provides further evidence that the quadpill strategy is superior to initial monotherapy by virtue of improved BP-lowering, less need for uptitration and being associated with less treatment inertia.

Keywords: Hypertension; Medication Adherence; Quality of Health Care.

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Conflict of interest statement

Competing interests: The George Institute for Global Health (TGI) has submitted patent applications in respect of low fixed-dose combination products for the treatment of cardiovascular or cardiometabolic disease. AR and CC are listed as inventors. AR is employed by TGI and seconded part-time to George Medicines Pty Ltd (GM). George Health Enterprises Pty Ltd (GHE) and its subsidiary, GM, have received investment funds to develop fixed-dose combination products, including combinations of blood pressure-lowering drugs. GHE is the social enterprise arm of TGI. AR and CC do not have direct financial interests in these patent applications or investments. The other authors report no conflicts.

Figures

Figure 1
Figure 1. Adjusted automated systolic blood pressure (SBP) across time pooled and by trial.
Figure 2
Figure 2. Interaction analysis of automated systolic blood pressure (SBP).
See this image and copyright information in PMC

References

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