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How quickly should we titrate antihypertensive medication? Systematic review modelling blood pressure response from trial data
  1. Daniel S Lasserson1,
  2. Thierry Buclin2,
  3. Paul Glasziou1,3
  1. 1Department of Primary Health Care, University of Oxford, Headington, Oxford, UK
  2. 2Division of Clinical Pharmacology and Toxicology, University of Lausanne, Hospital Beaumont, Switzerland
  3. 3Centre for Research in Evidence-Based Practice, Faculty of Health Sciences and Medicine, Bond University, Australia
  1. Correspondence to Dr D S Lasserson, Department of Primary Health Care, University of Oxford, Old Road Campus, Headington, Oxford OX3 7LF, UK; daniel.lasserson{at}


Context 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.

Study selection Trials that initiated antihypertensive medication as single therapy in hypertensive patients who were either drug naive or had a placebo washout from previous drugs.

Data extraction 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.

Results and 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.

  • EBM
  • pharmacokinetics/pharmacodynamics
  • primary care

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  • See Editorial, p 1721

  • Funding The study was funded by the National Institute for Health Research School for Primary Care Research.

  • Competing interests All authors have completed the Unified Competing Interest form at (available on request from the corresponding author) and declare: no relationships with any company that might have an interest in the submitted work in the previous 3 years; their spouses, partners, or children have no financial relationships that may be relevant to the submitted work; and no non-financial interests that may be relevant to the submitted work.

  • Provenance and peer review Not commissioned; externally peer reviewed.

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