Hydrochlorothiazide and atenolol combination antihypertensive therapy: Effects of drug initiation order

J. A. Johnson, Y. Gong, K. R. Bailey, R. M. Cooper-Dehoff, A. B. Chapman, S. T. Turner, G. L. Schwartz, K. Campbell, S. Schmidt, A. L. Beitelshees, E. Boerwinkle, J. G. Gums

Research output: Contribution to journalArticlepeer-review

22 Scopus citations


For combination antihypertensive therapy with thiazide diuretics and Β-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.

Original languageEnglish (US)
Pages (from-to)533-539
Number of pages7
JournalClinical Pharmacology and Therapeutics
Issue number5
StatePublished - Nov 2009
Externally publishedYes

ASJC Scopus subject areas

  • Pharmacology
  • Pharmacology (medical)


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