Efficacy and toxicity of antihypertensive pharmacotherapy relative to effective dose 50

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 redu...

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Bibliographic Details
Published in:British journal of clinical pharmacology 2019-10, Vol.85 (10), p.2218-2227
Main Authors: Dimmitt, Simon B., Stampfer, Hans G., Martin, Jennifer H., Ferner, Robin E.
Format: Article
Language:English
Subjects:
antihypertensive
Antihypertensive Agents - administration & dosage
Antihypertensive Agents - adverse effects
Blood Pressure - drug effects
Dose-Response Relationship, Drug
dose‐response
Drug Therapy, Combination
heart failure
Heart Failure - prevention & control
Humans
hypertension
Hypertension - drug therapy
Medication Adherence
polypill
Reviews‐themed Issue
Review‐themed Issue
stroke
Stroke - prevention & control
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Summary: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.
ISSN:0306-5251
1365-2125
DOI:10.1111/bcp.14033