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

Research output: Contribution to journalArticlepeer-review


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 languageEnglish
Pages (from-to)1668-1677
Number of pages10
JournalHypertension Research
Issue number6
StatePublished - Jun 2024


  • Federally qualified health centers
  • Hypertension
  • Quadpill
  • Randomized trial
  • Single pill combination


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