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

Priya Tripathi, Mark D Huffman, Donald M Lloyd-Jones, Clara K Chow, Jody D Ciolino, Jairo Mejia, James J Paparello, Stephen D Persell, Namratha R Kandula, My H Vu, Aashima Chopra, Sadiya S Khan, Alema Jackson, Adriana Quintana, Fallon M Flowers, Hiba Abbas, Danielle Lazar, Abigail S Baldridge

Journal: Hypertension research : official journal of the Japanese Society of Hypertension 2024;47(6):1668-1677

PMID: 38584159

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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.

Address: Cardiovascular Division and Global Health Center, Washington University in St. Louis, St. Louis, MO, USA. [email protected].; The George Institute for Global Health, University of New South Wales, Sydney, NSW, Australia. [email protected].; Department of Preventive Medicine, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA. [email protected].; Department of Preventive Medicine, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA.; Bluhm Cardiovascular Institute, Northwestern Medicine, Chicago, IL, USA.; Access Community Health Network, Chicago, IL, USA.; Department of Preventive Medicine, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA.; Division of General Internal Medicine, Department of Medicine, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA.; Department of Preventive Medicine, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA.; Division of Cardiology, Department of Medicine, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA.; Division of General Internal Medicine, Department of Medicine, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA.; Center for Primary Care Innovation, Institute for Public Health and Medicine, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA.; Department of Preventive Medicine, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA.; Division of Nephrology and Hypertension, Department of Medicine, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA.; Department of Preventive Medicine, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA.; Westmead Applied Research Centre, University of Sydney, Westmead, NSW, Australia.; Department of Preventive Medicine, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA.; Northwestern University Data Analysis and Coordinating Center, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA.

DOI: 10.1038/s41440-024-01658-y

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MeSH Terms: Humans, Female, Male, Hypertension, Middle Aged, Biphenyl Compounds, Antihypertensive Agents, Double-Blind Method, Benzimidazoles, Amlodipine, Tetrazoles, Blood Pressure, Aged, Treatment Outcome, Bisoprolol, Indapamide, Adult, Drug Therapy, Combination