Pooled randomised QUARTET trials assessing effectiveness of a single pill for hypertension

Hypertension is a major cause of premature death worldwide, controlled by only one in five adults. Two trials (Australia and USA) found a single quadpill containing a quarter dosage of four classes of medication effective in reducing blood pressure (BP) among participants with hypertension. By pooling these trials, we can estimate the overall benefit of the quadpill and its heterogeneity across subgroups and two important barriers for BP control: clinician medication inertia and participant medication adherence.

In a prespecified pooled individual participant data analysis of two QUARTET randomised, multicentre, double-blinded trials in people with hypertension using ≤1medication, quadpill (irbesartan (37.5 mg) (Australia)/candesartan (2 mg) (USA)), amlodipine (1.25 mg), indapamide (0.625 mg), bisoprolol (2.5 mg) unattended office systolic BP (SBP) at 12 weeks was compared with initial monotherapy (irbesartan (150 mg) (Australia), candesartan (8 mg) (USA)). Heterogeneity was assessed using an interaction term in the mixed cox model. Adherence, ≥80% pill count and treatment inertia were estimated.

In 653 participants (Australia, 591 (91%); USA, 62 (9%)) a significant drop in mean SBP (6.5 mm Hg (95% CI 4.8 to 8.8; p<0·001)) and diastolic BP (5.6 mm Hg (95% CI 4.5 to 6.9; p<0.001)) in favour of the quadpill was found, with less need for uptitration (p<0.001) and less treatment inertia (non-significant: p=0.303). Adherence was high for both treatment arms (over 80%). Compared with monotherapy, the quadpill effect varied by ethnicity (SBP reduced by White (6.9 mm Hg; 95% CI 4.7 to 9.2), Hispanic (3.3 mm Hg; 95% CI 4.0 to 10.6), Asian (12.3 mm Hg; 95% CI 6.2 to 18.5) and Black/other (1.4 mm Hg; 95% CI -9.0 to 6.3), interaction p=0.032).

This prospective individual participant data pooled analysis provides further evidence that the quadpill strategy is superior to initial monotherapy by virtue of improved BP-lowering, less need for uptitration and being associated with less treatment inertia.