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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.<\/jats:p>","DOI":"10.1111\/bcp.14033","type":"journal-article","created":{"date-parts":[[2019,6,20]],"date-time":"2019-06-20T10:23:55Z","timestamp":1561026235000},"page":"2218-2227","source":"Crossref","is-referenced-by-count":12,"title":["Efficacy and toxicity of antihypertensive pharmacotherapy relative to effective dose 50"],"prefix":"10.1111","volume":"85","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0093-4949","authenticated-orcid":false,"given":"Simon B.","family":"Dimmitt","sequence":"first","affiliation":[{"name":"Division of Internal Medicine, Medical School University of Western Australia  Crawley Western Australia Australia"},{"name":"University of Newcastle School of Medicine and Public Health  Callaghan New South Wales 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