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 - PubMed (original) (raw)

Observational Study

. 2019 Dec;28(12):1572-1582.

doi: 10.1002/pds.4884. Epub 2019 Sep 3.

Affiliations

Observational Study

Karine Marinier et al. Pharmacoepidemiol Drug Saf. 2019 Dec.

Abstract

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.

Keywords: blood pressure (BP) control; comparative effectiveness; hypertension; initial regimen; monotherapy; pharmacoepidemiology; propensity score; two-drug therapy.

© 2019 The Authors. Pharmacoepidemiology & Drug Safety Published by John Wiley & Sons Ltd.

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Conflict of interest statement

K.M., N.D., and M.d.C. are employees of Servier, a pharmaceutical company which manufactures blood‐pressure lowering agents. P.M. is an employee of IT&M Stats and currently works as a Servier contractor. N.P. has received financial support from several pharmaceutical companies which manufacture blood‐pressure lowering agents, for consultancy fees, research projects and staff, and for arranging and speaking at educational meetings. He holds no stocks and shares in any such companies. G.M. has received speaking fees from several companies (Servier, Menarini, Ferrer, Recordati, Merck Serono, Amgen, Medtronic, Fukuda), has been a member of advisory boards (Ferrer, Menarini, Sanofi). He holds no stocks or has no any other business participation in any such companies.

Figures

Figure 1

Figure 1

Patient flow chart. Abbreviations: ACEI, angiotensin‐converting enzyme inhibitors; ARB, angiotensin receptor blockers; BB, beta‐blockers; BP, blood pressure; CCB, calcium channel blockers; DBP, diastolic blood pressure; HES, Hospital Episode Statistics; ID, index date; MI, myocardial infarction; ONS, Office for National Statistics; Rx, prescription; SBP, systolic blood pressure; TIA, transient ischemic attack; TZD, thiazide and thiazide‐like diuretics.† reported diagnosis code before the index date and/or repeated elevated BP measures (defined as SBP ≥140 mmHg and/or DBP ≥90 mmHg) within a year before the index date.

Figure 2

Figure 2

Prescription patterns of antihypertensive drug class (es) in the study population at treatment initiation. Abbreviations: ACEi, angiotensin‐converting enzyme inhibitors; ARB, angiotensin receptor blockers; BB, beta‐blockers; CCB, calcium channel blockers; TZD, thiazide and thiazide‐like diuretics. [Colour figure can be viewed at

http://wileyonlinelibrary.com

]

Figure 3

Figure 3

Forest plots for blood pressure control. Abbreviations: ACEI, angiotensin‐converting enzyme inhibitors; AT, as treated; CCB, calcium channel blockers; HT, hypertension; ITT, intention‐to‐treat.

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