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Double-blind, placebo-controlled crossover comparison of five classes of antihypertensive drugs

Deary, Alison J.; Schumann, Anne L.; Murfet, Helen; Haydock, Stephen F.; Foo, Roger S.-Y.; Brown, Morris J.

Original papers: Therapeutic aspects

Objective  Hypertension guidelines recommend initial treatment with a β-blocker or diuretic and adding the other drug where blood pressure is not controlled. We hypothesized that systematic rotation through the major classes of antihypertensive drugs would demonstrate substantial differences in the pattern of an individual patient's response, and suggest a more rational approach to choosing best treatment.

Design  Thirty-four young hypertensives (age 28–55, median 47) rotated in a double-blind, Latin-square, crossover fashion through 6 weeks of treatment each with amlodipine, doxazosin, lisinopril, bisoprolol, bendrofluazide and placebo. Blood pressure was measured at each visit. ‘Best’ drug, defined by efficacy and tolerability, was repeated at the end.

Results  Rotation doubled the number of patients reaching target blood pressure (systolic < 140 mmHg) on one drug (P = 0.03). All five drugs were represented among the ‘best’ drugs. In six patients, the blood pressure on ‘best’ drug was at least 10 mmHg lower than on any other. Response to the ‘best’ drug was highly correlated (r = 0.79) with its previous administration. By contrast, there were only weak correlations between responses to pairs of drugs, except for angiotensin-converting enzyme (ACE) inhibitor (A) with β-blocker (B), and calcium blocker (C) with diuretic (D) – each r = 0.71, P< 0.005). In these young patients, the majority of patients (23/34) responded best to a drug suppressing the renin system (A and B).

Conclusions  Patients vary reproducibly in their response to initial treatment, and switching among drugs can increase the efficacy of monotherapy. The results support an AB/CD scheme for choosing therapy, in which the first drug is taken from one of these pairs, and uncontrolled patients switch to one of the other pair.

Clinical Pharmacology Unit, University of Cambridge, Addenbrooke's Hospital, Cambridge, UK.

Sponsorship: Funding was donated by Pfizer UK, which also provided double-blind medication with each of the drugs.

Correspondence* to Professor Morris J. Brown, Clinical Pharmacology Unit, Level 6, ACCI, Box 110, Addenbrooke's Hospital, Cambridge, CB2 2QQ, UK. Tel: +44 1223 336743; fax: +44 1223 762576; email:

Received 17 July 2001

Revised 9 November 2001

Accepted 6 December 2001

*Reprints will not be made available.

© 2002 Lippincott Williams & Wilkins, Inc.