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Randomized Controlled Trial
. 2024 Jun;47(6):1668-1677.
doi: 10.1038/s41440-024-01658-y. Epub 2024 Apr 8.

Efficacy and safety of a four-drug, quarter-dose treatment for hypertension: the QUARTET USA randomized trial

Mark D Huffman  1   2   3 , Abigail S Baldridge  4   5 , Danielle Lazar  6 , Hiba Abbas  6 , Jairo Mejia  6 , Fallon M Flowers  6 , Adriana Quintana  6 , Alema Jackson  6 , Namratha R Kandula  4   7 , Donald M Lloyd-Jones  4   8 , Stephen D Persell  7   9 , Sadiya S Khan  4   8 , James J Paparello  4   10 , Aashima Chopra  4 , Priya Tripathi  4 , My H Vu  4 , Clara K Chow  11 , Jody D Ciolino  4   12
Affiliations
Randomized Controlled Trial

Efficacy and safety of a four-drug, quarter-dose treatment for hypertension: the QUARTET USA randomized trial

Mark D Huffman et al. Hypertens Res. 2024 Jun.

Abstract

New approaches are needed to lower blood pressure (BP) given persistently low control rates. QUARTET USA sought to evaluate the effect of four-drug, quarter-dose BP lowering combination in patients with hypertension. QUARTET USA was a randomized (1:1), double-blinded trial conducted in federally qualified health centers among adults with hypertension. Participants received either a quadpill of candesartan 2 mg, amlodipine 1.25 mg, indapamide 0.625 mg, and bisoprolol 2.5 mg or candesartan 8 mg for 12 weeks. If BP was >130/>80 mm Hg at 6 weeks in either arm, then participants received open label add-on amlodipine 5 mg. The primary outcome was mean change in systolic blood pressure (SBP) at 12 weeks, controlling for baseline BP. Secondary outcomes included mean change in diastolic blood pressure (DBP), and safety included serious adverse events, relevant adverse drug effects, and electrolyte abnormalities. Among 62 participants randomized between August 2019-May 2022 (n = 32 intervention, n = 30 control), mean (SD) age was 52 (11.5) years, 45% were female, 73% identified as Hispanic, and 18% identified as Black. Baseline mean (SD) SBP was 138.1 (11.2) mmHg, and baseline mean (SD) DBP was 84.3 (10.5) mmHg. In a modified intention-to-treat analysis, there was no significant difference in SBP (-4.8 mm Hg [95% CI: -10.8, 1.3, p = 0.123] and a -4.9 mmHg (95% CI: -8.6, -1.3, p = 0.009) greater mean DBP change in the intervention arm compared with the control arm at 12 weeks. Adverse events did not differ significantly between arms. The quadpill had a similar SBP and greater DBP lowering effect compared with candesartan 8 mg. Trial registration number: NCT03640312.

Keywords: Federally qualified health centers; Hypertension; Quadpill; Randomized trial; Single pill combination.

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Conflict of interest statement

MDH has received travel support from the American Heart Association and World Heart Federation and consulting fees from PwC Switzerland. MDH has an appointment at The George Institute for Global Health, which has a patent, license, and has received investment funding with intent to commercialize fixed-dose combination therapy through its social enterprise business, George Medicines. MDH has pending patents for heart failure polypills. CKC has a patent for quarter-dose, quadruple drug combination therapy for blood pressure lowering. SDP receives unrelated research support from Omron Healthcare Co. Ltd. and honoraria for speaking from Omron Healthcare Co. and the National Committee for Quality Assurance. The remaining authors have nothing to disclose.

Figures

Fig. 1
Fig. 1
CONSORT flowchart of study participants
Fig. 2
Fig. 2
Box plots outlining temporal changes in distribution of systolic blood pressure (SBP) in (A) and distribution of diastolic blood pressures (DBP) by study arm in (B). Asterisk represents the mean value
See this image and copyright information in PMC

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