ABSTRACT

Introduction: Previous studies have suggested that more intensive initial therapy for
hypertension results in better long-term blood pressure (BP) control. We test this hypothesis
comparing initial monotherapy with dual therapy in the management of essential hypertension.

Methods and analysis: The study is a prospective, multicentre, double-blind, active-controlled
trial in patients with essential hypertension. Around 50% of patients studied will be newly
diagnosed and the others will be known hypertensives who previously received only
monotherapy. The trial is divided into three phases as follows: Phase 1 (Week 0–Week 16):
Randomised, parallel-group, masked assignation to either combination or monotherapy. Phase 2
(Week 17–Week 32): Open-label combination therapy. Phase 3 (Week 33–Week 52): Open-label
combination therapy plus open-label add-on (if BP is above 140/90 mm Hg). Hierarchical
primary end points are: a comparison of home BP (home systolic blood pressure (HSBP))
averaged over the duration of phase 1 and 2 in the combination versus monotherapy arms. If
combination is superior in this analysis, then the averaged mean HSBP between initial
monotherapy and initial combination therapy at the end of phase 2 will be compared. Secondary
end points include: BP control at 1 year; the role of age, baseline renin, sodium status, plasma
volume, haemodynamic compensation and peripheral resistance on BP control; validation of the
National Institute for Clinical Excellence/British Hypertension Society joint guideline algorithm;
safety and tolerability of combination therapy; and the impact of combination versus
monotherapy on left ventricular mass and aortic pulse wave velocity. A sample size of 536 (268
in each group) will have 90% power to detect a difference in means of 4 mm Hg.

Ethics and dissemination: PATHWAY 1 was approved by UK ethics (REC Reference
09/H0308/132). Trial results will be published and all participating subjects will be informed of
the results.

Trial registration number: UKCRN 4499 and EudraCT number 2008-007749-29 registered
27/08/2009.

 

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