Double-blind, placebo-controlled crossover comparison of five classes of antihypertensive drugs.
OBJECTIVE
Hypertension guidelines recommend initial treatment with a beta-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.


METHODS
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 beta-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.
Deary
Alison J
AJ
Clinical Pharmacology Unit, University of Cambridge, Addenbrooke's Hospital, Cambridge, UK.
Schumann
Anne L
AL
Murfet
Helen
H
Haydock
Stephen F
SF
Foo
Roger S-Y
RS
Brown
Morris J
MJ
D000317:Adrenergic alpha-Antagonists / Q000008:administration & dosage; D000319:Adrenergic beta-Antagonists / Q000008:administration & dosage; D000328:Adult; D017311:Amlodipine / Q000008:administration & dosage; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000008:administration & dosage; D000959:Antihypertensive Agents / Q000008:administration & dosage* / Q000009:adverse effects / Q000145:classification*; D001539:Bendroflumethiazide / Q000008:administration & dosage; D017298:Bisoprolol / Q000008:administration & dosage; D001794:Blood Pressure / Q000187:drug effects; D002121:Calcium Channel Blockers / Q000008:administration & dosage; D018592:Cross-Over Studies; D004232:Diuretics; D004311:Double-Blind Method; D017292:Doxazosin / Q000008:administration & dosage; D005260:Female; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D006973:Hypertension / Q000188:drug therapy* / Q000503:physiopathology; D017706:Lisinopril / Q000008:administration & dosage; D008297:Male; D008875:Middle Aged; D020097:Natriuretic Peptide, Brain / Q000097:blood; D012084:Renin-Angiotensin System / Q000187:drug effects; D049993:Sodium Chloride Symporter Inhibitors / Q000008:administration & dosage
D000317:Adrenergic alpha-Antagonists; D000319:Adrenergic beta-Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors; D000959:Antihypertensive Agents; D002121:Calcium Channel Blockers; D004232:Diuretics; D049993:Sodium Chloride Symporter Inhibitors; D020097:Natriuretic Peptide, Brain; D017311:Amlodipine; D001539:Bendroflumethiazide; D017706:Lisinopril; D017292:Doxazosin; D017298:Bisoprolol