title: Effect of dose and combination of antihypertensives on interindividual blood pressure variability: a systematic review.
abstract: OBJECTIVE
  Recent studies have shown that visit-to-visit blood pressure variability is a powerful risk factor for stroke, is reduced by calcium channel blockers and diuretics, and increased by β-blockers. However, it is unknown whether these effects are dose-dependent and persist in combination with other drugs.
  
  
  METHODS
  Cochrane and Medline databases were searched for systematic reviews and randomized controlled trials of antihypertensive drugs. Eligible trials randomized all patients to a combination of drug classes or different doses of the same drug. Baseline and follow-up data for mean (SD) systolic blood pressure (SBP) and diastolic blood pressure were extracted. Differences in interindividual variance (SD2) in blood pressure were expressed as a ratio (VR). Estimates were pooled by random-effects meta-analysis.
  
  
  RESULTS
  Calcium channel blockers reduced interindividual variability in SBP when added to another agent (VR, 0.75; 95% CI, 0.64 to 0.87; P=0.0002; 12 trials; 1565 patients) with a smaller reduction with diuretics (VR, 0.85; 0.71 to 1.01; P=0.07; 17 trials; 3217 patients). Adding other agents to calcium channel blockers did not significantly affect SBP variability (VR, 1.06; 0.83 to 1.34; P=0.65; 12 trials; 1460 patients) despite a 5.8-mm Hg reduction in mean SBP. Randomization to a higher dose of calcium channel blockers reduced SBP variability (VR, 0.84; 0.74 to 0.94; P=0.004; 25 trials; 2179 patients), whereas randomization to a higher dose of β-blockers increased SBP variability (VR, 1.31; 1.01 to 1.69; P=0.034; 6 trials; 486 patients).
  
  
  CONCLUSIONS
  Effects of antihypertensive drugs on SBP variability are dose-dependent and persist when used in combinations. Use of a high dose of a calcium channel blocker alone or in combination with other agents is therefore likely to be particularly effective in prevention of stroke.
authors.affiliation: Stroke Prevention Research Unit, Department of Clinical Neurology, University of Oxford, and John Radcliffe Hospital, Headington, Oxford OX3 9DU, UK.
authors.forename: Alastair John Stewart
authors.initials: AJ
authors.lastname: Webb
authors.forename: Peter Malcolm
authors.initials: PM
authors.lastname: Rothwell
mesh_terms: D000959:Antihypertensive Agents / Q000008:administration & dosage* / Q000627:therapeutic use; D001794:Blood Pressure / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D004359:Drug Therapy, Combination; D006801:Humans; D006973:Hypertension / Q000188:drug therapy*
chemical_list: D000959:Antihypertensive Agents