Effectiveness of two-drug therapy versus monotherapy as initial regimen in hypertension: A propensity score-matched cohort study in the UK Clinical Practice Research Datalink

Purpose To compare the effectiveness on blood pressure (BP) of initial two-drug therapy versus monotherapy in hypertensive patients. Methods Using the Clinical Practice Research Datalink, linked with Hospital Episode Statistics and Office for National Statistics, we identified a cohort of adults with uncontrolled hypertension, initiating one or two antihypertensive drug classes between 2006 and 2014. New users of two drugs and monotherapy were matched 1:2 by propensity score. Main exposure was "as-treated," ie, until first regimen change. Primary and secondary endpoints were systolic and diastolic BP control and major adverse cardiovascular event (MACE), respectively. Hazard ratios (HR) and 95% confidence intervals (CI) were estimated using Cox proportional hazard models. Results Of 54 523 eligible patients, 3256 (6.0%) were initiated to a two-drug combination. Of these, 2807 were matched to 5614 monotherapy users. Mean exposure duration was 12.7 months, with 76.5% patients changing their initial regimen. Two-drug therapy was associated with a clinically significant BP control increase in all hypertensive patients (HR = 1.17 [95%CI: 1.09-1.26]), more so in patients with grade 2-3 hypertension (HR = 1.28 [1.17-1.41]). An increase of 27% in BP control (HR = 1.27 [1.08-1.49]) was observed in patients initiating an ACEi+CCB combination compared with initiators of either single class. No significant association was found between two-drug therapy and MACE. Several sensitivity analyses confirmed the main findings. Conclusions Few patients initiated therapy with two drugs, reflecting UK guidelines' recommendation to start with monotherapy. This study supports the greater effectiveness of two-drug therapy as the initial regimen for BP control.