title: How quickly should we titrate antihypertensive medication? Systematic review modelling blood pressure response from trial data.
abstract: BACKGROUND
  There are no evidence syntheses available to guide clinicians on when to titrate antihypertensive medication after initiation.
  
  
  OBJECTIVE
  To model the blood pressure (BP) response after initiating antihypertensive medication. Data sources electronic databases including Medline, Embase, Cochrane Register and reference lists up to December 2009.
  
  
  METHODS
  Trials that initiated antihypertensive medication as single therapy in hypertensive patients who were either drug naive or had a placebo washout from previous drugs.
  
  
  METHODS
  Office BP measurements at a minimum of two weekly intervals for a minimum of 4 weeks. An asymptotic approach model of BP response was assumed and non-linear mixed effects modelling used to calculate model parameters.
  
  
  CONCLUSIONS
  Eighteen trials that recruited 4168 patients met inclusion criteria. The time to reach 50% of the maximum estimated BP lowering effect was 1 week (systolic 0.91 weeks, 95% CI 0.74 to 1.10; diastolic 0.95, 0.75 to 1.15). Models incorporating drug class as a source of variability did not improve fit of the data. Incorporating the presence of a titration schedule improved model fit for both systolic and diastolic pressure. Titration increased both the predicted maximum effect and the time taken to reach 50% of the maximum (systolic 1.2 vs. 0.7 weeks; diastolic 1.4 vs. 0.7 weeks).
  
  
  CONCLUSIONS
  Estimates of the maximum efficacy of antihypertensive agents can be made early after starting therapy. This knowledge will guide clinicians in deciding when a newly started antihypertensive agent is likely to be effective or not at controlling BP.
authors.affiliation: Department of Primary Health Care, University of Oxford, Old Road Campus, Headington, Oxford OX3 7LF, UK. daniel.lasserson@phc.ox.ac.uk
authors.forename: Daniel S
authors.initials: DS
authors.lastname: Lasserson
authors.forename: Thierry
authors.initials: T
authors.lastname: Buclin
authors.forename: Paul
authors.initials: P
authors.lastname: Glasziou
mesh_terms: D000959:Antihypertensive Agents / Q000008:administration & dosage* / Q000494:pharmacology / Q000627:therapeutic use; D001794:Blood Pressure / Q000187:drug effects; D004334:Drug Administration Schedule; D016903:Drug Monitoring / Q000379:methods*; D006801:Humans; D006973:Hypertension / Q000188:drug therapy* / Q000503:physiopathology; D016032:Randomized Controlled Trials as Topic; D013997:Time Factors
chemical_list: D000959:Antihypertensive Agents