Optimisation of antihypertensive treatment by crossover rotation of four major classes

Background. Most comparisons of antihypertensive drugs are undertaken in pa rallel groups. We undertook a crossover rotation of the four main classes o f antihypertensive drugs, in untreated young hypertensive patients, to asse ss the response rate with monotherapy achieved by a systematic rotation. Methods. 56 patients, mean blood pressure 161/98 mm Hg, entered the relatio n, of whom 36 received all four monthly cycles of treatment with an angiote nsin-converting-enzyme (ACE) inhibitor (A), beta-blocker (B), calcium-chann el blocker (C), and diuretic (D). Each patient's best drug was then repeate d to assess repeatability. Two measures of individual variability in respon se were used. First, the value of rotation was measured by the increased pr oportion of patients reaching target blood pressure on their best drug vers us their first drug. Second, we assessed whether the responses to each drug were correlated with each other. Findings. Significant variability in response was found. 20 of the 41 patie nts reaching target blood pressure (less than or equal to 140/90 mm Hg) fai led to achieve this target on their first drug, Relation increased from 22/ 56 (39%) to 41/56 (73%) the success of monotherapy (p = 0.0001); in half th e patients, blood-pressure on the best treatment was 135/85 mm Hg or less. There were significant correlations between the blood pressure responses to A and B (r = 0.5, p < 0.01), and C and D (r = 0.6, p < 0.001), but not bet ween the other four pairings of treatments. The responses to the AB pair we re, on average, at least 50% higher than those to the CD pair; this differe nce was highly significant by multivariate repeated-measures ANOVA. Interpretation. There is a marked variability in hypertensive patients' res ponse to different antihypertensive drugs. The basis may be underlying vari ability in types of essential hypertension. Optimisation of treatment requi res systematic rotation through several therapies; however, an "AB/CD" rule is proposed in which one of each of the two pairs of treatments is initial ly selected to abbreviate the rotation in routine practice.