Efficacy and toxicity of antihypertensive pharmacotherapy relative to effective dose 50

Simon Dimmitt, HG Stampfer, Jennifer Martin, Robin Ferner

    Research output: Contribution to journalArticlepeer-review

    2 Citations (Scopus)

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

    Keywords

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

    Fingerprint

    Dive into the research topics of 'Efficacy and toxicity of antihypertensive pharmacotherapy relative to effective dose 50'. Together they form a unique fingerprint.

    Cite this