Quadruple UltrA-low-dose tReaTment for hypErTension - QUARTET USA

Contribution To Literature:

The QUARTET USA trial showed that a strategy of quarter dosing of four antihypertensive medications into one polypill (“quadpill”) was not superior to full-dose ARB monotherapy in improving BP control among patients with mild to moderate hypertension.


The goal of the trial was to assess the efficacy and safety of a polypill containing quarter doses of four antihypertensive medications for hypertension compared with angiotensin receptor blocker (ARB) monotherapy.

Study Design

This was a randomized, controlled, parallel-group trial over 12 weeks in Chicago, Illinois. Eligible patients were randomized in 1:1 fashion to either a polypill (n = 32) or candesartan 8 mg (n = 30). The polypill contained bisoprolol 2.5 mg, candesartan 2 mg, amlodipine 1.25 mg, and indapamide 0.625 mg. Patients in the ARB arm also received add-on amlodipine 5 mg daily if blood pressure (BP) was above goal.

  • Total consented: 120
  • Total randomized: 62
  • Total with 12-week follow-up: 53
  • Mean patient age: 52 years
  • Percentage female: 45%

Inclusion criteria:

  • Age ≥18 years
  • Diagnosis of hypertension among two groups: treatment naïve: 140-179/90-109 mm Hg, or current monotherapy: 130-159/85-99 mm Hg

Other salient features/characteristics:

  • Hispanic ethnicity: 73%
  • Black race: 18%
  • Baseline monotherapy: 77%

Principal Findings:

The primary outcome, mean change in automated systolic BP, for polypill vs. monotherapy, was: -4.8 mm Hg (95% confidence interval -10.7 to 1.2 mm Hg, p > 0.05).

Secondary outcomes for polypill vs. monotherapy:

  • Adjusted mean change in diastolic BP at 12 weeks: -4.9 mm Hg (p > 0.05)
  • Add on amlodipine: 18.8% vs. 53.3%
  • Any serious adverse event: 6.3% vs. 0
  • Adverse event leading to discontinuation: 6.3% vs. 26.7%


The results of this trial indicate that a treatment strategy of ultra-low dosing of four BP-lowering medications did not lead to a statistically greater BP reduction versus standard-dose ARB monotherapy for patients with mild to moderate hypertension. Adverse events were more common in the intervention arm, although discontinuation rates were higher in the control arm. Due to COVID-19, the enrollment target could not be achieved, and this limited sample size led to low power. These findings were consistent with the international QUARTET trial and suggest a potential use of a low-dose antihypertensive polypill for patients with hypertension. Next steps will include evaluating a hypertensive polypill to assess clinical outcomes.


Presented by Dr. Mark D. Huffman at the American Heart Association Scientific Sessions, Chicago, IL, November 6, 2022.

Clinical Topics: Diabetes and Cardiometabolic Disease, Prevention, Hypertension

Keywords: AHA Annual Scientific Sessions, AHA22, Amlodipine, Angiotensin Receptor Antagonists, Antihypertensive Agents, Bisoprolol, Blood Pressure, Blood Pressure Monitoring, Ambulatory, Hypertension, Metabolic Syndrome, Polypharmacy, Primary Prevention, Treatment Outcome

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