1. ¹College of Pharmacy, University of Florida, Gainesville, Florida, USA
2. ²College of Medicine, University of Florida, Gainesville, Florida, USA
3. ³Center for Pharmacogenomics, University of Florida, Gainesville, Florida, USA
4. ⁴Mayo Clinic College of Medicine, Rochester, Minnesota, USA
5. ⁵Emory University School of Medicine, Atlanta, Georgia, USA
6. ⁶University of Maryland College of Medicine, Baltimore, Maryland, USA
7. ⁷University of Texas at Houston Center for Human Genetics, Houston, Texas, USA

Correspondence: JA Johnson, (Johnson@cop.ufl.edu)

Received 9 March 2009; Accepted 27 April 2009; Published online 1 July 2009.

Abstract

For combination antihypertensive therapy with thiazide diuretics and -blockers, the effect of the order of initiation of the drugs on the outcome has not been tested. Patients with uncomplicated hypertension were randomized to receive either hydrochlorothiazide (HCTZ) or atenolol monotherapy, followed by addition of the alternative drug. Blood pressure (BP) responses were evaluated by race and order of drug initiation. A total of 368 participants received combination therapy. Among the participants, blacks showed a greater BP-lowering effect than whites did with HCTZ monotherapy (-13.0/-7.4 mm Hg vs. -8.0/-4.2 mm Hg, P < 0.001) but a smaller BP-lowering effect than did whites with atenolol monotherapy (-1.1/-2.9 mm Hg vs. -9.9/-9.2 mm Hg, P < 0.0001). These differences were not evident during combination therapy. However, both groups showed greater response to HCTZ + atenolol than to atenolol + HCTZ (-19.1/-14.2 mm Hg vs. -15.6/-11.3 mm Hg, P < 0.0001). Despite optimal dosing of HCTZ + atenolol, only two-thirds of the participants achieved BP control. In HCTZ/atenolol combination antihypertensive therapy, the order in which the drugs are initiated affects total BP lowering during the first 4–6 months of therapy.