Quadruple UltrA-low-dose tReaTment for hypErTension - QUARTET

Contribution To Literature:

The QUARTET trial showed that a strategy of quarter dosing of four antihypertensive medications into one polypill (“quadpill”) is superior to full-dose monotherapy with irbesartan in improving BP control among patients with a diagnosis of HTN on no medications or therapy with only one medication at baseline.

Description:

The goal of the trial was to assess the efficacy and safety of a polypill/quadpill containing quarter doses of four antihypertensive medications compared with monotherapy among patients with hypertension (HTN).

Study Design

Eligible patients were randomized in a double-blind 1:1 fashion to either a quadpill (n = 300) or irbesartan 150 mg (n = 291). The quadpill contained bisoprolol 2.5 mg, irbesartan 37.5 mg, amlodipine 1.25 mg, and indapamide 0.625 mg.

  • Total screened: 743
  • Total number of enrollees: 591
  • Duration of follow-up: 52 weeks
  • Mean patient age: 59 years
  • Percentage female: 40%

Inclusion criteria:

  • Age ≥18 years
  • Diagnosis of HTN, and
  • Criteria A: Untreated HTN ≥4 weeks with clinic systolic blood pressure (SBP) ≥140/90 mm Hg or daytime 24-hour ambulatory BP (ABP) ≥135/85 mm Hg
  • Criteria B: Monotherapy for HTN with clinic SBP ≥130/85 mm Hg or daytime ABP ≥125/80 mm Hg

Exclusion criteria:

  • Contraindication to study drugs
  • Secondary causes of HTN
  • Concomitant illness
  • Breastfeeding, women not on contraception

Other salient features/characteristics:

  • White race: 82%
  • No BP medications at baseline: 54%
  • Mean office BP: 153/89 mm Hg

Principal Findings:

The primary outcome, unattended office SBP for quadpill vs. monotherapy at week 12, was 121/71 mm Hg vs. 127/79 mm Hg; mean difference in SBP was -6.9 mm Hg (p < 0.01).

Secondary outcomes for quadpill vs. monotherapy:

  • Mean difference in diastolic BP (DBP) at week 12: -5.8 mm Hg (p < 0.0001)
  • BP control <140/90 mm Hg at week 12: 76% vs. 58% (p < 0.0001)
  • Mean difference in SBP/DBP at week 52: -7.8/-6 mm Hg (p < 0.0001)
  • Dizziness at week 12: 31% vs. 25.4% (p = 0.08)
  • Serum creatinine at week 12: 0.9 vs. 0.85 mg/dl (p = 0.006)

Interpretation:

The results of this trial indicate that a strategy of quarter dosing of four antihypertensive medications into one polypill (“quadpill”) is superior to full-dose monotherapy with irbesartan for improving BP control among patients with a diagnosis of HTN on no medications or therapy with only one medication at baseline. Due to COVID-19, the total enrollment target could not be achieved. Side effects were more or less similar, with a small (but likely clinically insignificant) increase in serum creatinine and potassium with the quadpill approach. The trial was not powered for clinical endpoints. It adds to the body of favorable literature on a polypill approach for the management of chronic cardiovascular conditions. This may be particularly useful among elderly patients where polypharmacy and HTN undertreatment both tend to be common.

References:

Chow CK, Atkins ER, Hillis GS, et al., on behalf of the QUARTET Investigators. Initial treatment with a single pill containing quadruple combination of quarter doses of blood pressure medicines versus standard dose monotherapy in patients with hypertension (QUARTET): a phase 3, randomized, double-blind, active-controlled trial. Lancet 2021;Aug 29:[Epub ahead of print].

Presented by Dr. Clara Chow at the European Society of Cardiology Virtual Congress, August 27, 2021.

Clinical Topics: Diabetes and Cardiometabolic Disease, Prevention, Hypertension

Keywords: ESC21, ESC Congress, Antihypertensive Agents, Blood Pressure, Blood Pressure Monitoring, Ambulatory, Creatinine, Hypertension, Metabolic Syndrome, Polypharmacy, Primary Prevention, Treatment Outcome


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