BackgroundOral anticoagulation in addition to antiplatelet treatment after an acute coronary syndrome might reduce ischaemic events but increase bleeding risk. We performed a meta-analysis to evaluate the efficacy and safety of adding direct thrombin or factor-Xa inhibition by any of the novel oral anticoagulants (apixaban, dabigatran, darexaban, rivaroxaban, and ximelagatran) to single (aspirin) or dual (aspirin and clopidogrel) antiplatelet therapy in this setting.Methods and resultsAll seven published randomized, placebo-controlled phase II and III studies of novel oral anticoagulants in acute coronary syndromes were included. The database consisted of 30 866 patients, 4135 (13.4%) on single, and 26 731 (86.6%) on dual antiplatelet therapy, with a non-ST- or ST-elevation acute coronary syndrome within the last 7–14 days. We defined major adverse cardiovascular events (MACEs) as the composite of all-cause mortality, myocardial infarction, or stroke; and clinically significant bleeding as the composite of major and non-major bleeding requiring medical attention according to the study definitions. When compared with aspirin alone the combination of an oral anticoagulant and aspirin reduced the incidence of MACE [hazard ratio (HR) and 95% confidence interval 0.70; 0.59–0.84], but increased clinically significant bleeding (HR: 1.79; 1.54–2.09). Compared with dual antiplatelet therapy with aspirin and clopidogrel, adding an oral anticoagulant decreased the incidence of MACE modestly (HR: 0.87; 0.80–0.95), but more than doubled the bleeding (HR: 2.34; 2.06–2.66). Heterogeneity between studies was low, and results were similar when restricting the analysis to phase III studies.ConclusionIn patients with a recent acute coronary syndrome, the addition of a new oral anticoagulant to antiplatelet therapy results in a modest reduction in cardiovascular events but a substantial increase in bleeding, most pronounced when new oral anticoagulants are combined with dual antiplatelet therapy.

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A few studies have examined biomarkers in patients with myocardial infarction (MI) and peripheral artery disease (PAD), i.e. multisite artery disease (MSAD). The aim of the study was firstly, to associate biomarkers with the occurrence of PAD/MSAD and secondly, if those can, in addition to clinical characteristics, identify MI patients with MSAD.In two prospectively observational studies including unselected patients with recent MI, PAD was defined as an abnormal ankle-brachial index (ABI) score (<0.9 or >1.4). The proximity extension assay (PEA) technique was used, simultaneously analyzing 92 biomarkers with association to cardiovascular disease. Biomarkers were tested for univariate associations with PAD. Random forest was used to identify biomarkers with a higher association to PAD. The additional discriminatory accuracy of adding biomarkers to clinical characteristics was analyzed by the cstatistics. Nine biomarkers were identified as significantly associated with MSAD/PAD in the primary patient cohort, analyzed early after the MI. In the prediction analysis, six biomarkers were identified associated with PAD. Three of these; Tumor necrosis factor receptor (TNFR-1), Tumor necrosis factor receptor 2 (TNFR-2) and Growth Differentiation Factor 15 (GDF-15) improved c-statistics when added to clinical characteristics from 0.683 (95% CI 0.610-0.756) to 0.715 (95% CI 0.645-0.784) in the primary patient cohort with a similar result, 0.729 (95% CI 0.687-0.770) to 0.752 (95% CI 0.771-0.792) in the secondary patient cohort. Biomarkers associated with inflammatory pathways are associated with MSAD in MI patients. Three biomarkers of 92; TNFR-1, TNFR-2 and GDF-15, in this exploratory added information in the prediction of MSAD and emphasis the importance of further studies.

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Objectives To evaluate whether the Walking Impairment Questionnaire score could identify patients with polyvascular disease in a population with recent myocardial infarction and their association with cardiovascular events during two-year follow-up. Design A prospective observational study. Setting Patients admitted to the acute coronary care unit, the Department of Cardiology, Uppsala University Hospital. Participants Patients admitted with acute Non-STEMI- or STEMI-elevation myocardial infarction. Main outcome measures The Walking Impairment Questionnaire, developed as a self-administered instrument to assess walking distance , speed , and stair climbing in patients with peripheral artery disease, predicts future cardiovascular events and mortality. Two hundred and sixty-three patients with recent myocardial infarction answered Walking Impairment Questionnaire. Polyvascular disease was defined as abnormal findings in the coronary- and carotid arteries and an abnormal ankle–brachial index. The calculated score for each of all three categories were divided into quartiles with the lowest score in first quartile. Results The lowest (worst) quartile in all three Walking Impairment Questionnaire categories was associated with polyvascular disease, fully adjusted; distance , odds ratio (OR) 5.4 (95% confidence interval (CI) 1.8–16.1); speed , OR 7.4 (95% CI 1.5–36.5); stair climbing , OR 8.4 (95% CI 1.0–73.6). In stair climbing score , patients with the lowest (worst) score had a higher risk for the composite cardiovascular endpoint compared to the highest (best) score; hazard ratio 5.3 (95% CI 1.5–19.0). The adherence to medical treatment was high (between 81.7% and 99.2%). Conclusions The Walking Impairment Questionnaire is a simple tool to identify myocardial infarction patients with more widespread atherosclerotic disease and although well treated medically, stair climbing predicts cardiovascular events.

Background Peripheral artery disease (PAD) is associated with increased risk of cardiovascular events and mortality. PAD is underdiagnosed in patients admitted for myocardial infarction (MI). Purpose To evaluate whether biomarkers in addition to clinical characteristics could improve the identification of PAD in MI patients. Methods Two prospectively observational studies including unselected patients with recent ST-elevation or non-ST elevation MI were used for the analyses. PAD was defined as abnormal ankle brachial indexes (ABI) score (<0.9 or >1.4) on at least one side. The Proximity Extension Assay (PEA) technique was used to simultaneously analyze 92 biomarkers with association to cardiovascular disease (CVD I and III, Olink Proteomics) in samples early after the acute MI. Random forest was used to identify the biomarkers with higher association to PAD. The discriminating accuracy of adding biomarkers to clinical characteristics including age, sex, diabetes mellitus, hypertension and smoking were analyzed by the c-statistic. Results In the REBUS cohort (n=420) the mean age was 67 years, 22.1% were women, 26.4% were smoking, 16.2% had diabetes and 53.3% hypertension. In the VAMIS cohort (n=998) the mean age was 71 years, 33.5% were women, 19.9% were smoking, 18.1% and 49.9% had diabetes and hypertension, respectively. PAD was found in 20.0% and 22.8% of the patients in the REBUS and VAMIS cohort, respectively. Six biomarkers associated with PAD (Tnfrsf 14, tnf r2, tnf r1, GDF-15, IL-6 ra, ctsd) were identified in the REBUS cohort and validated in the VAMIS cohort. Additional predictive value of the biomarkers compared to the performance of the model with clinical characteristics, as measured by the c-statistic Clinical characteristics (CC) CC + Tnfrsf14 CC + Tnf r2 CC + Tnf r1 CC + GDF-15 CC + IL-6 ra CC + ctsd REBUS (n=420) 0.683 (0.610,0.756) 0.702 (0.632, 0.772) 0.703 (0.633, 0.773) 0.709 (0.640, 0.779) 0.710 (0.640, 0.781) 0.682 (0.608, 0.775) 0.683 (0.610, 0.757) VaMIS (n=998) 0.729 (0.687, 0.770) 0.732 (0.691, 0.733) 0.745 (0.704, 0.785) 0.746 (0.706, 0.787) 0.752 (0.711, 0.792) 0.729 (0.688, 0.770) 0.736 (0.695, 0.777) Tnfrsf 14 = tumor necrosis factor receptor superfamily member 14; Tnf r2 = tumor necrosis factor receptor 2; Tnf r1 = tumor necrosis factor receptor 1; GDF-15 = growth differentiation factor 15; IL-6 ra = interleukin-6 receptor subunit alpha; ctsd = Cathepsin D. Conclusion Out of a large panel of biomarkers, tumor necrosis factor and its receptors and GDF-15 were identified associated with PAD in MI patients. In this underdiagnosed manifestation of atherosclerosis in MI patients, clinical characteristics are strong predictors of PAD, but the cytokines may have an additional value. Further studies focusing on more widespread atherosclerosis in acute coronary syndrome might identify a patient group with benefit of treatment targeting inflammation. Acknowledgement/Funding None