Optimisation of antihypertensive treatment by crossover rotation of four major classes

Lancet. 1999 Jun 12;353(9169):2008-13. doi: 10.1016/s0140-6736(98)07614-4.


Background: Most comparisons of antihypertensive drugs are undertaken in parallel groups. We undertook a crossover rotation of the four main classes of antihypertensive drugs, in untreated young hypertensive patients, to assess the response rate with monotherapy achieved by a systematic rotation.

Methods: 56 patients, mean blood pressure 161/98 mm Hg, entered the rotation, of whom 36 received all four monthly cycles of treatment with an angiotensin-converting-enzyme (ACE) inhibitor (A), beta-blocker (B), calcium-channel blocker (C), and diuretic (D). Each patient's best drug was then repeated to assess repeatability. Two measures of individual variability in response were used. First, the value of rotation was measured by the increased proportion of patients reaching target blood pressure on their best drug versus 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 patients reaching target blood pressure (< or =140/90 mm Hg) failed to achieve this target on their first drug. Rotation increased from 22/56 (39%) to 41/56 (73%) the success of monotherapy (p=0.0001); in half the 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 between the other four pairings of treatments. The responses to the AB pair were, on average, at least 50% higher than those to the CD pair; this difference was highly significant by multivariate repeated-measures ANOVA.

Interpretation: There is a marked variability in hypertensive patients' response to different antihypertensive drugs. The basis may be underlying variability in types of essential hypertension. Optimisation of treatment requires systematic rotation through several therapies; however, an "AB/CD" rule is proposed in which one of each of the two pairs of treatments is initially selected to abbreviate the rotation in routine practice.

Publication types

  • Clinical Trial
  • Comparative Study
  • Controlled Clinical Trial

MeSH terms

  • Adrenergic beta-Antagonists / therapeutic use
  • Adult
  • Angiotensin-Converting Enzyme Inhibitors / therapeutic use
  • Antihypertensive Agents / therapeutic use*
  • Blood Pressure / drug effects
  • Calcium Channel Blockers / therapeutic use
  • Cross-Over Studies
  • Diuretics / therapeutic use
  • Humans
  • Hypertension / drug therapy*
  • Hypertension / physiopathology
  • Middle Aged


  • Adrenergic beta-Antagonists
  • Angiotensin-Converting Enzyme Inhibitors
  • Antihypertensive Agents
  • Calcium Channel Blockers
  • Diuretics