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

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

doi:10.1038/s41440-024-01658-y

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

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

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

5 Scopus citations

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. (Figure presented.)

Original language	English (US)
Pages (from-to)	1668-1677
Number of pages	10
Journal	Hypertension Research
Volume	47
Issue number	6
DOIs	https://doi.org/10.1038/s41440-024-01658-y
State	Published - Jun 2024

Funding

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. The study was supported by the National Heart, Lung, and Blood Institute (R61/R33HL139852), National Center for Advancing Translational Sciences (UL1TR001422), and Northwestern University Feinberg School of Medicine. The funders were not involved in the development of the study design; collection, management, analysis, and interpretation of data; writing of the report; and the decision to submit the report for publication. The program officers representing the National Heart, Lung, and Blood Institute participated in Data and Safety Monitoring Board activities (ex officio, non-voting).

Keywords

Federally qualified health centers
Hypertension
Quadpill
Randomized trial
Single pill combination

ASJC Scopus subject areas

Internal Medicine
Physiology
Cardiology and Cardiovascular Medicine

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Huffman, M. D., Baldridge, A. S., Lazar, D., Abbas, H., Mejia, J., Flowers, F. M., Quintana, A., Jackson, A., Kandula, N. R., Lloyd-Jones, D. M., Persell, S. D., Khan, S. S., Paparello, J. J., Chopra, A., Tripathi, P., Vu, M. H., Chow, C. K., & Ciolino, J. D. (2024). Efficacy and safety of a four-drug, quarter-dose treatment for hypertension: the QUARTET USA randomized trial. Hypertension Research, 47(6), 1668-1677. https://doi.org/10.1038/s41440-024-01658-y

@article{963e127e17404b878ac47d37e8a96eed,

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

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. (Figure presented.)",

keywords = "Federally qualified health centers, Hypertension, Quadpill, Randomized trial, Single pill combination",

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

note = "Publisher Copyright: {\textcopyright} The Author(s) 2024.",

year = "2024",

month = jun,

doi = "10.1038/s41440-024-01658-y",

language = "English (US)",

volume = "47",

pages = "1668--1677",

journal = "Hypertension Research",

issn = "0916-9636",

publisher = "Springer Nature",

number = "6",

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Huffman, MD, Baldridge, AS, Lazar, D, Abbas, H, Mejia, J, Flowers, FM, Quintana, A, Jackson, A, Kandula, NR, Lloyd-Jones, DM, Persell, SD , Khan, SS , Paparello, JJ, Chopra, A, Tripathi, P, Vu, MH, Chow, CK & Ciolino, JD 2024, 'Efficacy and safety of a four-drug, quarter-dose treatment for hypertension: the QUARTET USA randomized trial', Hypertension Research, vol. 47, no. 6, pp. 1668-1677. https://doi.org/10.1038/s41440-024-01658-y

TY - JOUR

T1 - Efficacy and safety of a four-drug, quarter-dose treatment for hypertension

T2 - the QUARTET USA randomized trial

AU - Huffman, Mark D.

AU - Baldridge, Abigail S.

AU - Lazar, Danielle

AU - Abbas, Hiba

AU - Mejia, Jairo

AU - Flowers, Fallon M.

AU - Quintana, Adriana

AU - Jackson, Alema

AU - Kandula, Namratha R.

AU - Lloyd-Jones, Donald M.

AU - Persell, Stephen D.

AU - Khan, Sadiya S.

AU - Paparello, James J.

AU - Chopra, Aashima

AU - Tripathi, Priya

AU - Vu, My H.

AU - Chow, Clara K.

AU - Ciolino, Jody D.

PY - 2024/6

Y1 - 2024/6

N2 - 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. (Figure presented.)

AB - 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. (Figure presented.)

KW - Federally qualified health centers

KW - Hypertension

KW - Quadpill

KW - Randomized trial

KW - Single pill combination

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

Abstract

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