Outcomes of non-invasive diagnostic modalities for the detection of coronary artery disease: network meta-analysis of diagnostic randomised controlled trials

Objective: To evaluate differences in downstream testing, coronary revascularisation, and clinical outcomes following non-invasive diagnostic modalities used to detect coronary artery disease. Design: Systematic review and network meta-analysis. Data sources: Medline, Medline in process, Embase, Cochrane Library for clinical trials, PubMed, Web of Science, SCOPUS, WHO International Clinical Trials Registry Platform, and Clinicaltrials.gov. Eligibility criteria for selecting studies: Diagnostic randomised controlled trials comparing non-invasive diagnostic modalities in patients presenting with symptoms suggestive of low risk acute coronary syndrome or stable coronary artery disease. Data synthesis: A random effects network meta-analysis synthesised available evidence from trials evaluating the effect of non-invasive diagnostic modalities on downstream testing and patient oriented outcomes in patients with suspected coronary artery disease. Modalities included exercise electrocardiograms, stress echocardiography, single photon emission computed tomography-myocardial perfusion imaging, real time myocardial contrast echocardiography, coronary computed tomographic angiography, and cardiovascular magnetic resonance. Unpublished outcome data were obtained from 11 trials. Results: 18 trials of patients with low risk acute coronary syndrome (n=11 329) and 12 trials of those with suspected stable coronary artery disease (n=22 062) were included. Among patients with low risk acute coronary syndrome, stress echocardiography, cardiovascular magnetic resonance, and exercise electrocardiograms resulted in fewer invasive referrals for coronary angiography than coronary computed tomographic angiography (odds ratio 0.28 (95% confidence interval 0.14 to 0.57), 0.32 (0.15 to 0.71), and 0.53 (0.28 to 1.00), respectively). There was no effect on the subsequent risk of myocardial infarction, but estimates were imprecise. Heterogeneity and inconsistency were low. In patients with suspected stable coronary artery disease, an initial diagnostic strategy of stress echocardiography or single photon emission computed tomography-myocardial perfusion imaging resulted in fewer downstream tests than coronary computed tomographic angiography (0.24 (0.08 to 0.74) and 0.57 (0.37 to 0.87), respectively). However, exercise electrocardiograms yielded the highest downstream testing rate. Estimates for death and myocardial infarction were imprecise without clear discrimination between strategies. Conclusions: For patients with low risk acute coronary syndrome, an initial diagnostic strategy of stress echocardiography or cardiovascular magnetic resonance is associated with fewer referrals for invasive coronary angiography and revascularisation procedures than non-invasive anatomical testing, without apparent impact on the future risk of myocardial infarction. For suspected stable coronary artery disease, there was no clear discrimination between diagnostic strategies regarding the subsequent need for invasive coronary angiography, and differences in the risk of myocardial infarction cannot be ruled out. Systematic review registration: PROSPERO registry no CRD42016049442

Prediction of cardiovascular risk using Framingham, ASSIGN and QRISK2: how well do they predict individual rather than population risk?

BACKGROUND: The objective of this study was to evaluate the performance of risk scores (Framingham, Assign and QRISK2) in predicting high cardiovascular disease (CVD) risk in individuals rather than populations. METHODS AND FINDINGS: This study included 1.8 million persons without CVD and prior statin prescribing using the Clinical Practice Research Datalink. This contains electronic medical records of the general population registered with a UK general practice. Individual CVD risks were estimated using competing risk regression models. Individual differences in the 10-year CVD risks as predicted by risk scores and competing risk models were estimated; the population was divided into 20 subgroups based on predicted risk. CVD outcomes occurred in 69,870 persons. In the subgroup with lowest risks, risk predictions by QRISK2 were similar to individual risks predicted using our competing risk model (99.9% of people had differences of less than 2%); in the subgroup with highest risks, risk predictions varied greatly (only 13.3% of people had differences of less than 2%). Larger deviations between QRISK2 and our individual predicted risks occurred with calendar year, different ethnicities, diabetes mellitus and number of records for medical events in the electronic health records in the year before the index date. A QRISK2 estimate of low 10-year CVD risk (<15%) was confirmed by Framingham, ASSIGN and our individual predicted risks in 89.8% while an estimate of high 10-year CVD risk (≥ 20%) was confirmed in only 48.6% of people. The majority of cases occurred in people who had predicted 10-year CVD risk of less than 20%. CONCLUSIONS: Application of existing CVD risk scores may result in considerable misclassification of high risk status. Current practice to use a constant threshold level for intervention for all patients, together with the use of different scoring methods, may inadvertently create an arbitrary classification of high CVD risk

External validation of a COPD prediction model using population-based primary care data: a nested case-control study

Emerging models for predicting risk of chronic obstructive pulmonary disease (COPD) require external validation in order to assess their clinical value. We validated a previous model for predicting new onset COPD in a different database. We randomly drew 38,597 case-control pairs (total N = 77,194) of individuals aged ≥35 years and matched for sex, age, and general practice from the United Kingdom Clinical Practice Research Datalink database. We assessed accuracy of the model to discriminate between COPD cases and non-cases by calculating area under the receiver operator characteristic (ROC(AUC)) for the prediction scores. Analogous to the development model, ever smoking (OR 6.70; 95%CI 6.41–6.99), prior asthma (OR 6.43; 95%CI 5.85–7.07), and higher socioeconomic deprivation (OR 2.90; 95%CI 2.72–3.09 for highest vs. lowest quintile) increased the risk of COPD. The validated prediction scores ranged from 0–5.71 (ROC(AUC) 0.66; 95%CI 0.65–0.66) for males and 0–5.95 (ROC(AUC) 0.71; 95%CI 0.70–0.71) for females. We have confirmed that smoking, prior asthma, and socioeconomic deprivation are key risk factors for new onset COPD. Our model seems externally valid at identifying patients at risk of developing COPD. An impact assessment now needs to be undertaken to assess whether this prediction model can be applied in clinical care settings

A systematic review of intervention effects on potential mediators of children\u27s physical activity

Background : Many interventions aiming to increase children&rsquo;s physical activity have been developed and implemented in a variety of settings, and these interventions have previously been reviewed; however the focus of these reviews tends to be on the intervention effects on physical activity outcomes without consideration of the reasons and pathways leading to intervention success or otherwise. To systematically review the efficacy of physical activity interventions targeting 5-12 year old children on potential mediators and, where possible, to calculate the size of the intervention effect on the potential mediator. Methods : A systematic search identified intervention studies that reported outcomes on potential mediators of physical activity among 5-12 year old children. Original research articles published between 1985 and April 2012 were reviewed. Results : Eighteen potential mediators were identified from 31 studies. Positive effects on cognitive/psychological potential mediators were reported in 15 out of 31 studies. Positive effects on social environmental potential mediators were reported in three out of seven studies, and no effects on the physical environment were reported. Although no studies were identified that performed a mediating analysis, 33 positive intervention effects were found on targeted potential mediators (with effect sizes ranging from small to large) and 73% of the time a positive effect on the physical activity outcome was reported. Conclusions : Many studies have reported null intervention effects on potential mediators of children&rsquo;s physical activity; however, it is important that intervention studies statistically examine the mediating effects of interventions so the most effective strategies can be implemented in future programs

Living network meta-analysis compared with pairwise meta-analysis in comparative effectiveness research: empirical study.

Objectives To examine whether the continuous updating of networks of prospectively planned randomised controlled trials (RCTs) (‘living’ network meta-analysis) provides strong evidence against the null hypothesis in comparative effectiveness of medical interventions earlier than the updating of conventional, pairwise meta-analysis. Design Empirical study of the accumulating evidence about the comparative effectiveness of clinical interventions. Data Sources Database of network meta-analyses of RCTs identified through searches of MEDLINE, EMBASE, and the Cochrane Database of Systematic Reviews until April 14, 2015. Eligibility criteria for study selection Network meta-analyses published after January 2012 that compared at least five treatments and included at least 20 RCTs. Clinical experts were asked to identify in each network the treatment comparisons of greatest clinical interest. We excluded comparisons for which direct and indirect evidence disagreed, based on side-splitting test P&lt;0.10. Outcomes and analysis For each selected comparison we performed cumulative pairwise and network meta-analyses. We constructed monitoring boundaries of statistical significance and considered the evidence against the null hypothesis as strong when the monitoring boundaries were crossed. We defined a significance level α=5%, power of 90% (β=10%) and an anticipated treatment effect to detect equal to the final estimate from the network meta-analysis. We compared the frequency and time to strong evidence against the null hypothesis between pairwise and network meta-analyses. Results Forty-nine comparisons of interest from 44 networks were included; the majority (n=39, 80%) were between active drugs, mainly from cardiology, endocrinology, psychiatry and rheumatology. Twenty-nine comparisons were informed by both direct and indirect evidence (59%), 13 comparisons by indirect (27%) and seven by direct evidence (14%) only. Both network and pairwise meta-analysis provided strong evidence against the null hypothesis for seven comparisons but for an additional ten comparisons only network meta-analysis provided strong evidence against the null hypothesis (P=0.002). The median time to strong evidence against the null hypothesis was 19 years with living network meta-analysis and 23 years with living pairwise meta-analysis (hazard ratio 2.78 (95% CI 1.00 to 7.72), P=0.05). Studies directly comparing the treatments of interest continued to be published for 8 comparisons after strong evidence had become evident in network meta-analysis. Conclusions In comparative effectiveness research, prospectively planned living network meta-analyses produced strong evidence against the null hypothesis more often and earlier than conventional, pairwise meta-analyses. </p

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Life of King Edward VI