BackgroundNaltrexone is an opioid antagonist used in many different conditions, both licensed and unlicensed. It is used at widely varying doses from 3 to 250 mg. The aim of this review was to extensively evaluate the safety of oral naltrexone by examining the risk of serious adverse events and adverse events in randomised controlled trials of naltrexone compared to placebo.MethodsA systematic search of the Cochrane Central Register of Controlled Trials, MEDLINE, Embase, other databases and clinical trials registries was undertaken up to May 2018. Parallel placebo-controlled randomised controlled trials longer than 4 weeks published after 1 January 2001 of oral naltrexone at any dose were selected. Any condition or age group was included, excluding only studies in opioid or ex-opioid users owing to possible opioid/opioid antagonist interactions. The systematic review used the guidance of the Cochrane Handbook and Preferred Reporting Items for Systematic Reviews and Meta-analyses harms checklist throughout. Numerical data were independently extracted by two people and cross-checked. Risk of bias was assessed with the Cochrane risk-of-bias tool. Meta-analyses were performed in R using random effects models throughout.ResultsEighty-nine randomised controlled trials with 11,194 participants were found, studying alcohol use disorders (n = 38), various psychiatric disorders (n = 13), impulse control disorders (n = 9), other addictions including smoking (n = 18), obesity or eating disorders (n = 6), Crohn’s disease (n = 2), fibromyalgia (n = 1) and cancers (n = 2). Twenty-six studies (4,960 participants) recorded serious adverse events occurring by arm of study. There was no evidence of increased risk of serious adverse events for naltrexone compared to placebo (risk ratio 0.84, 95% confidence interval 0.66–1.06). Sensitivity analyses pooling risk differences supported this conclusion (risk difference −0.01, 95% confidence interval −0.02–0.00) and subgroup analyses showed that results were consistent across different doses and disease groups. Secondary analysis revealed only six marginally significant adverse events for naltrexone compared to placebo, which were of mild severity.ConclusionsNaltrexone does not appear to increase the risk of serious adverse events over placebo. These findings confirm the safety of oral naltrexone when used in licensed indications and encourage investments to undertake efficacy studies in unlicensed indications.Trial registrationPROSPERO 2017 CRD42017054421.Electronic supplementary materialThe online version of this article (10.1186/s12916-018-1242-0) contains supplementary material, which is available to authorized users.

Background and objective Hypertension, hyperlipidaemia, diabetes mellitus, smoking and family history are established risk factors for coronary artery disease. This study sought to determine the diagnostic value these factors have in patients presenting to an emergency department (ED) with suspected acute myocardial infarction (AMI). Design, settings and analysis This secondary analysis of a prospective diagnostic test accuracy study took place across 14 hospitals in England. A total of 1273 patients, presenting with suspected cardiac chest pain, were included for analysis - 179 (14.1%) had an adjudicated diagnosis of AMI. Outcome measure and analysis AMI diagnosis was adjudicated with serial troponin testing conducted on arrival and 3–12 hours later. The presence of any risk factors was documented at the time of initial presentation. Results The post-test probability of AMI in the absence of risk factors (9.7%) shifts to only 23.5% when 4–5 factors are present. Associations of risk factors with AMI diagnosis were found as follows; hypertension [odds ratio (OR) 1.47, confidence interval (CI) 1.07–2.02], hyperlipidaemia (OR 1.57, CI 1.14–2.16), diabetes mellitus (OR 1.51, CI 1.04–2.20), smoking (OR 1.51, CI 1.05–2.17) and family history (OR 0.98, CI 0.71–1.37). The area under the receiver operating characteristic curve was 0.58. Conclusion Traditional cardiac risk factors have limited association with AMI in the ED, but an increasing risk factor burden is associated with increasing prevalence of AMI. These findings suggest that future work to refine existing decision aids used in this patient group may be of value.

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