Applied mediation analyses:a review and tutorial

In recent years, mediation analysis has emerged as a powerful tool to disentangle causal pathways from an exposure/treatment to clinically relevant outcomes. Mediation analysis has been applied in scientific fields as diverse as labour market relations and randomized clinical trials of heart disease treatments. In parallel to these applications, the underlying mathematical theory and computer tools have been refined. This combined review and tutorial will introduce the reader to modern mediation analysis including: the mathematical framework; required assumptions; and software implementation in the R package medflex. All results are illustrated using a recent study on the causal pathways stemming from the early invasive treatment of acute coronary syndrome, for which the rich Danish population registers allow us to follow patients’ medication use and more after being discharged from hospital

Use of diagnostic coronary angiography in women and men presenting with acute myocardial infarction:a matched cohort study

BACKGROUND: Based on evident sex-related differences in the invasive management of patients presenting with acute myocardial infarction (AMI), we sought to identify predictors of diagnostic coronary angiography (DCA) and to investigate reasons for opting out an invasive strategy in women and men. METHODS: The study was designed as a matched cohort study. We randomly selected 250 female cases from a source population of 4000 patients hospitalized with a first AMI in a geographically confined region of Denmark from January 2010 to November 2011. Each case was matched to a male control on age and availability of cardiac invasive facilities at the index hospital. We systematically reviewed medical records for risk factors, comorbid conditions, clinical presentation, and receipt of DCA. Clinical justifications, as stated by the treating physician, were noted for the subset of patients who did not receive a DCA. RESULTS: Overall, 187 women and 198 men received DCA within 60 days (75 % vs. 79 %, hazard ratio: 0.82 [0.67-1.00], p = 0.047).In the subset of patients who did not receive a DCA (n = 114), clinical justifications for opting out an invasive strategy was not documented for 21 patients (18.4 %). Type 2 myocardial infarction was noted in 11 patients (women versus men; 14.5 % vs. 3.8 %, p = 0.06) and identified as a potential confounder of the sex-DCA relationship. Receipt of DCA was predicted by traditional risk factors for ischaemic heart disease (family history of cardiovascular disease, hypercholesterolemia, and smoking) and clinical presentation (chest pain, ST-segment elevations). Although prevalent in both women and men, the presence of relative contraindications did not prohibit the use of DCA. CONCLUSION: In this matched cohort of patients with a first AMI, women and men had different clinical presentations despite similar age. However, no differences in the distribution of relative contraindications for DCA were found between the sexes. Type 2 MI posed a potentiel confounder for the sex-related differences in the use of DCA. Importantly,clinical justification for opting out an invasive strategy was not documented in almost one fifth of patients not receiving a DCA. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12872-016-0248-9) contains supplementary material, which is available to authorized users

Underuse of an invasive strategy for patients with diabetes with acute coronary syndrome:a nationwide study

BACKGROUND: Guidelines recommend an early invasive strategy for patients with diabetes with acute coronary syndromes (ACS). We investigated if patients with diabetes with ACS are offered coronary angiography (CAG) and revascularisation to the same extent as patients without diabetes. METHODS AND RESULTS: The study is a nationwide cohort study linking Danish national registries containing information on healthcare. The study population comprises all patients hospitalised with first-time ACS in Denmark during 2005–2007 (N=24 952). Diabetes was defined as claiming of a prescription for insulin and/or oral hypoglycaemic agents within 6 months prior to the ACS event. Diabetes was present in 2813 (11%) patients. Compared with patients without diabetes, patients with diabetes were older (mean 69 vs 67 years, p<0.0001), less often males (60% vs 64%, p=0.0001) and had more comorbidity. Fewer patients with diabetes underwent CAG: cumulative incidence 64% vs 74% for patients without diabetes, HR=0.72 (95% CI 0.69 to 0.76, p<0.0001); adjusted for age, sex, previous revascularisation and comorbidity HR=0.78 (95% CI 0.74 to 0.82, p<0.0001). More patients with diabetes had CAG showing two-vessel or three-vessel disease (53% vs 38%, p<0.0001). However, revascularisation after CAG revealing multivessel disease was less likely in patients with diabetes (multivariable adjusted HR=0.76, 95% CI 0.68 to 0.85, p<0.0001). CONCLUSIONS: In this nationwide cohort of patients with incident ACS, patients with diabetes were found to be less aggressively managed by an invasive treatment strategy. The factors underlying the decision to defer an invasive strategy in patients with diabetes are unclear and merit further investigation

Reperfusion therapy for ST elevation acute myocardial infarction 2010/2011: current status in 37 ESC countries

Aims Primary percutaneous coronary intervention (PPCI) is the preferred reperfusion therapy in ST-elevation myocardial infarction (STEMI). We conducted this study to evaluate the contemporary status on the use and type of reperfusion therapy in patients admitted with STEMI in the European Society of Cardiology (ESC) member countries. Methods and results A cross-sectional descriptive study based on aggregated country-level data on the use of reperfusion therapy in patients admitted with STEMI during 2010 or 2011. Thirty-seven ESC countries were able to provide data from existing national or regional registries. In countries where no such registries exist, data were based on best expert estimates. Data were collected on the use of STEMI reperfusion treatment and mortality, the numbers of cardiologists, and the availability of PPCI facilities in each country. Our survey provides a brief data summary of the degree of variation in reperfusion therapy across Europe. The number of PPCI procedures varied between countries, ranging from 23 to 884 per million inhabitants. Primary percutaneous coronary intervention and thrombolysis were the dominant reperfusion strategy in 33 and 4 countries, respectively. The mean population served by a single PPCI centre with a 24-h service 7 days a week ranged from 31 300 inhabitants per centre to 6 533 000 inhabitants per centre. Twenty-seven of the total 37 countries participated in a former survey from 2007, and major increases in PPCI utilization were observed in 13 of these countries. Conclusion Large variations in reperfusion treatment are still present across Europe. Countries in Eastern and Southern Europe reported that a substantial number of STEMI patients are not receiving any reperfusion therapy. Implementation of the best reperfusion therapy as recommended in the guidelines should be encourage

Developments in the invasive diagnostic-therapeutic cascade of women and men with acute coronary syndromes from 2005 to 2011:a nationwide cohort study

OBJECTIVES: To investigate for trends in sex-related differences in the invasive diagnostic–therapeutic cascade in a population of patients with acute coronary syndromes (ACS). DESIGN: A nationwide cohort study. SETTING: Administrative and clinical registries covering all hospitalisations, invasive cardiac procedures and deaths in the Danish population of 5.6 million inhabitants. PARTICIPANTS: We included 52 565 patients aged 30–90 years who were hospitalised with a first ACS from January 2005 to November 2011. Follow-up was 60 days from the day of index admission. MAIN OUTCOME MEASURES: Diagnostic coronary angiography, percutaneous coronary intervention or coronary artery bypass within 60 days of index admission. RESULTS: Women constituted 36%, were older, had more comorbidity and were less likely to be admitted to a hospital with cardiac catheterisation facilities than men. Mortality rates were similar for both sexes. Diagnostic coronary angiography was performed less frequently on women compared with men, both within 1 day (31% vs 42%; p<0.001) and within 60 days (67% vs 80%; p<0.001), yielding adjusted female–male HRs of 0.83 (0.79–0.87) and 0.86 (0.84–0.89), respectively.Among the 39 677 patients undergoing coronary angiography, non-obstructive coronary artery disease was more frequent among women than men (22% vs 9%; p<0.001). Women were less likely to undergo percutaneous coronary intervention (58% vs 72%; p<0.001) and coronary artery bypass (6% vs 11%, p<0.001) within 60 days than men, yielding adjusted HRs of 0.96 (0.92–0.99) and 0.81 (0.74–0.89), respectively. The sex-related differences were not attenuated over time for any of the invasive cardiac procedures (p values for trend >0.05). CONCLUSIONS: In this nationwide study, men were more likely to undergo an invasive approach than women when hospitalised with a first ACS—a difference persisting from 2005 to 2011. Future studies should focus on the potential mechanisms behind this differential treatment