Efficacy and safety of a quadruple ultra-low-dose treatment for hypertension (QUARTET USA): Rationale and design for a randomized controlled trial

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

doi:10.1016/j.ahj.2022.09.004

Cited by 9 publications

(5 citation statements)

References 23 publications

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“…To support wider implementation of a four-drug, quarter-dose combination therapy approach, our study team also conducted an explanatory sequential, mixed methods process evaluation of the trial among patients and healthcare professionals [ 17 ]. This treatment approach was considered acceptable and convenient, despite the tension that patients reported related to necessity and concerns of blood pressure lowering medications.…”

Section: Discussionmentioning

confidence: 99%

“…The methods for the QUARTET USA trial have been published [ 17 ]. Briefly, the study used a type I hybrid, phase II randomized (1:1), double-blind trial design to evaluate efficacy and safety of a quarter-dose combination of four blood pressure lowering drugs with a corresponding process evaluation to understand factors related to trial implementation and study drug acceptability.…”

Section: Methodsmentioning

confidence: 99%

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

Huffman,

Baldridge,

Lazar

et al. 2024

Hypertens Res

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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.

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Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

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

Huffman,

Baldridge,

Lazar

et al. 2024

Hypertens Res

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“…Although a combination of antihypertensive medications can lower blood pressure more effectively than a single medication [6], about 40% of patients with hypertension, including those with uncontrolled blood pressure, still receive antihypertensive monotherapy [7]. Furthermore, a more active regimen with a quadruple low-dose antihypertensive single-pill combination (SPC) can be used as an initial treatment to achieve optimal blood pressure control [8][9][10][11][12]. The rationale underlying the benefits of combination therapy is that combination therapy can effectively activate different complementary pathophysiological pathways, and the incidence of adverse events (AEs) following combination therapy may be reduced because the effects of each agent are reciprocally counterbalanced [13].…”

Section: Introductionmentioning

confidence: 99%

A Randomized, Multicenter, Double-blind, Placebo-Controlled Study to Evaluate the Efficacy and Safety of a Quadruple Combination of Amlodipine, Losartan, Rosuvastatin, and Ezetimibe in Patients with Concomitant Essential Hypertension and Dyslipidemia

Kim

Ahn

Kim

et al. 2023

Am J Cardiovasc Drugs

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Background Few data are available regarding the efficacy and safety of a single-pill combination (SPC) consisting of four medications in patients with concomitant hypertension and dyslipidemia. Objective We aimed to determine the efficacy and tolerability of a fixed-dose SPC consisting of 5 mg amlodipine, 100 mg losartan, 20 mg rosuvastatin, and 10 mg ezetimibe (A/L/R/E) in patients with concomitant hypertension and dyslipidemia. Methods This was a 14-week, randomized, multicenter, double-blind, placebo-controlled, phase III clinical trial. In total, 145

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“…This trial investigated whether treatment with LDQT containing candesartan, 2 mg, amlodipine, 1.25 mg, indapamide, 0.625 mg, and bisoprolol, 2.5 mg, once daily, achieved blood pressure control more effectively, and with fewer adverse effects at 12 weeks, compared with standard monotherapy with candesartan, 8 mg, once daily. 16 In this report, we present the findings of the QUARTET USA clinical trial process evaluation, which explores patient and health care provider perceptions about LDQT as a novel strategy for hypertension treatment. Understanding patient‐centered mechanisms of the LDQT strategy is important for achieving widespread blood pressure control.…”

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confidence: 99%

Process Evaluation of a Double‐Blind Randomized Controlled Trial to Assess the Efficacy and Safety of a Quadruple Ultra‐Low‐Dose Treatment for Hypertension Within a Federally Qualified Health Center Network (QUARTET USA)

Sanuade,

Jacobson,

Quintana

et al. 2024

JAHA

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Background This convergent parallel‐design mixed‐methods process evaluation of the QUARTET USA (Quadruple Ultra‐Low‐Dose Treatment for Hypertension USA) clinical trial (NCT03640312) explores patient and health care professional perceptions about the use of low‐dose quadruple therapy (LDQT) as a novel strategy for hypertension management. Methods and Results A survey of all 62 patients enrolled in the QUARTET USA trial was conducted. A subsample of 13 patients and 11 health care professionals, recruited via purposive sampling, took part in semistructured interviews. At enrollment, 68% of participants (mean [SD] age, 51.7 [11.5] years; 56% self‐identified as Hispanic: Mexican ethnicity, 16% as Hispanic: other ethnicity, 16% as Black race, 8% as White race, and 1.6% as South Asian race) reported that their current health depended on blood pressure medications, and 48% were concerned about blood pressure medications. At trial completion, 80% were satisfied with LDQT, 96% were certain the benefits of taking LDQT outweighed the disadvantages, and 96% reported that LDQT was convenient to take. Both patients and health care professionals found LDQT acceptable because it reduced patients' perceived pill burden and facilitated medication adherence. Health care professionals stated that a perceived limitation of LDQT was the inability to titrate doses. Steps to facilitate LDQT implementation include introducing stepped‐care combinations and treatment protocols, inclusion in clinical practice guidelines, and eliminating patient cost barriers. Conclusions LDQT was an acceptable strategy for hypertension treatment among patients and health care professionals involved in the QUARTET USA clinical trial. Although LDQT was generally perceived as beneficial for maintaining patients' blood pressure control and facilitating adherence, some clinicians perceived limitations in titration inflexibility, adverse effects, and costs. Registration URL: https://www.clinicaltrials.gov ; Unique identifier: NCT03640312.

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Efficacy and safety of a quadruple ultra-low-dose treatment for hypertension (QUARTET USA): Rationale and design for a randomized controlled trial

Cited by 9 publications

References 23 publications

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

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

A Randomized, Multicenter, Double-blind, Placebo-Controlled Study to Evaluate the Efficacy and Safety of a Quadruple Combination of Amlodipine, Losartan, Rosuvastatin, and Ezetimibe in Patients with Concomitant Essential Hypertension and Dyslipidemia

Process Evaluation of a Double‐Blind Randomized Controlled Trial to Assess the Efficacy and Safety of a Quadruple Ultra‐Low‐Dose Treatment for Hypertension Within a Federally Qualified Health Center Network (QUARTET USA)

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