Quarter-Dose Quadruple Combination Therapy for Initial Treatment of Hypertension - Quadruple Combination Therapy

Contribution To Literature:

This trial showed that quadruple combination therapy was effective at lowering blood pressure.


The goal of the trial was to evaluate low-dose quadruple combination therapy compared with placebo among newly diagnosed hypertension patients.

Study Design

  • Randomized
  • Parallel
  • Placebo
  • Blinded
  • Crossover

Patients with newly diagnosed hypertension were randomized to quarter-dose quadruple combination therapy (irbesartan 37.5 mg, amlodipine 1.25 mg, hydrochlorothiazide 6.25 mg, atenolol 12.5 mg) versus placebo, which was administered by crossover design (n = 20).

  • Total number of enrollees: 20
  • Duration of follow-up: 10 weeks
  • Mean patient age: 58 years
  • Percentage female: 52%
  • Percentage with diabetes: 10%

Inclusion criteria:

  • Patients with newly diagnosed hypertension (systolic blood pressure >140 mm Hg)

Exclusion criteria:

  • Contraindication to at least one of the study medications
  • Severe or accelerated hypertension
  • Pregnancy
  • Inability to provide informed consent or limited life expectancy

Principal Findings:

The primary outcome, 24-hour systolic blood pressure, was 120 mm Hg in the active treatment group versus 138 mm Hg in the placebo group (p < 0.001).

Secondary outcomes:

  • Proportion with office blood pressure <140/90 mm Hg: 100% vs. 33%, respectively, for active treatment vs. placebo
  • Serious adverse events: 0 vs. 0


Among patients with newly diagnosed hypertension, the use of a quarter-dose quadruple combination therapy was effective at lowering blood pressure compared with placebo. This strategy was safe with no reported serious adverse events. Further research is needed to compare quarter-dose quadruple combination therapy compared with usual strategies for hypertension.


Chow CK, Thakkar J, Bennett A, et al. Quarter-dose quadruple combination therapy for initial treatment of hypertension: placebo-controlled, crossover, randomised trial and systematic review. Lancet 2017;389:1035-42.

Clinical Topics: Prevention, Statins, Hypertension

Keywords: Amlodipine, Atenolol, Blood Pressure, Hydrochlorothiazide, Hypertension, Primary Prevention, Treatment Outcome

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