How quickly should we titrate antihypertensive medication? Systematic review modelling blood pressure response from trial data

Heart. 2011 Nov;97(21):1771-5. doi: 10.1136/hrt.2010.221473. Epub 2011 May 17.


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.

Publication types

  • Meta-Analysis
  • Research Support, Non-U.S. Gov't
  • Review
  • Systematic Review

MeSH terms

  • Antihypertensive Agents / administration & dosage*
  • Antihypertensive Agents / pharmacology
  • Antihypertensive Agents / therapeutic use
  • Blood Pressure / drug effects
  • Drug Administration Schedule
  • Drug Monitoring / methods*
  • Humans
  • Hypertension / drug therapy*
  • Hypertension / physiopathology
  • Randomized Controlled Trials as Topic
  • Time Factors


  • Antihypertensive Agents