Efficacy and toxicity of antihypertensive pharmacotherapy relative to effective dose 50

Research output: Contribution to journalArticlepeer-review

Authors

  • Simon Dimmitt
  • HG Stampfer
  • Jennifer Martin
  • Robin Ferner

Colleges, School and Institutes

External organisations

  • Department of Medicine, Hunter New England Local Health District, Newcastle, Australia
  • University of Western Australia

Abstract

Antihypertensive drugs have usually been approved at doses near the top of their respective dose-response curves. Efficacy plateaus but adverse drug reactions (ADRs), such as falls, cerebral or renal ischaemia, increase as dose is increased, especially in older patients with comorbidities. ADRs reduce adherence and may be difficult to ascertain reliably. Higher doses have generally not been shown to reduce total mortality, which provides a summary of efficacy and safety. Weight loss and other lifestyle measures are essential and may be sufficient treatment in many young and low risk patients. Most antihypertensive drug lower systolic blood pressure by around 10 mmHg, which reduces stroke and heart failure by about a quarter. Clinical trials have not been designed to demonstrate specific blood pressure treatment thresholds and targets, which are mostly extrapolated from epidemiology. Mean population oral effective dose 50 may be the most appropriate dose at which to commence antihypertensive drugs. The dose can then be titrated up if greater efficacy is demonstrated, or lowered if ADRs develop. Lower dose combination therapy may best balance benefit and harms with fewer ADRs and additive, potentially synergistic, efficacy.

Details

Original languageEnglish
Pages (from-to)2218-2227
Number of pages10
JournalBritish Journal of Clinical Pharmacology
Volume85
Issue number10
Early online date19 Aug 2019
Publication statusPublished - 1 Oct 2019

Keywords

  • stroke, antihypertensive, dose-response, heart failure, hypertension, polypill