COMPARATIVE EFFECTIVENESS OF TWO-DRUG THERAPY VERSUS MONOTHERAPY AS INITIAL REGIMEN IN HYPERTENSION

Abstract

Objective: Clinical trials have shown initial combination therapy to be more effective on blood pressure (BP) control than initial monotherapy but few studies examined the question in a large primary care database. The main objective of this study was to evaluate relative effectiveness on BP of an initial two-drug therapy compared to monotherapy in hypertension (HT). Design and method: In the UK Clinical Practice Research Datalink with hospitalisation and mortality data linkage, we identified a cohort of adults with uncontrolled HT and initiating one or two antihypertensive drug class(es) (among ACEIs, ARBs, CCB, BB, thiazide-like diuretics) between 2006 and 2014, with follow-up until February 2016. New users of 2-drugs and monotherapy were matched 1:2 using a propensity score. Exposure was defined as intention-to-treat (ITT) or as treated (AT), i.e. until first regimen change. Primary and secondary endpoints were respectively BP control and serious cardiovascular event (SCE). Analyses in planned subgroups, according to HT severity or most frequent classes of drugs (ACEi, CCB) used specific propensity scores. Results: Among 54,523 eligible hypertensive patients included, 3,256 patients were initiated on 2 drugs of which 2,807 (86.2%) were matched to 5,614 monotherapy new users (mean SBP/DBP 164.6/94.8 mm Hg). During a mean follow-up (ITT) of 4.6 years, mean exposure duration (AT) was 12.7 months, with 76.5% patients changing initial regimen. In the AT analysis, use of 2 drugs was associated with 17% increased BP control in all hypertensive patients (HR [95%CI]: 1.17 [1.09–1.26]), increasing to 28% in patients with grade 2–3 HT (1.28 [1.17–1.41]), and 27% in patients with ACEi+CCB (1.27 [1.08–1.49]). A positive association was also observed in the ITT analysis of all hypertensive patients (1.08 [1.03–1.13]) or those with grade 2–3 HT (1.10 [1.03–1.18]). For SCE, overall no significant association with 2-drug therapy was found. Conclusions: In line with UK guidelines, only a small fraction of hypertensive patients used two drugs in combination as initial therapy. This large population-based cohort study supports the evidence of greater effectiveness of 2-drug therapy for BP control, while additional data would be required for SCE.