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Chronic total occlusion (CTO) percutaneous coronary intervention (PCI) has substantially improved due to increasing operator experience and advancements in equipment, techniques, and management algorithms. However, the overall benefit of CTO PCI remains controversial, particularly since only a few randomized trials have been reported to date. Methods: We performed a meta-analysis to evaluate the efficacy of CTO PCI. The study outcomes were the occurrence of all-cause mortality, myocardial infarction, repeat revascularization, stroke, or freedom from angina at the longest documented follow-up period. Results: In five trials including 1790 patients, the mean age was 63 ± 10 years, 17% were female, with a median follow-up of 2.9 years. The procedural success rate ranged from 73% to 97% and the right coronary artery was the most involved artery (52%). There was no significant difference between CTO PCI and no intervention regarding all-cause mortality (odds ratio [OR]: 1.10, 95% confidence interval [CI]: 0.49--2.47, P = 0.82), myocardial infarction (OR: 1.20, 95% CI: 0.81--1.77, P = 0.36), repeat revascularization (OR: 0.67, 95% CI: 0.40--1.14, P = 0.14), or stroke (OR: 0.60, 95% CI: 0.26--1.36, P = 0.22). In two trials including 686 patients, significantly more patients were free of angina at 1 year, defined as the Canadian Cardiovascular Society grading of angina pectoris Grade 0, in the CTO PCI group compared to the no intervention group (OR: 0.52, 95% CI: 0.35--0.76, P < 0.001). Meta-regression analyses based on various trial-level covariates (gender, diabetes, previous myocardial infarction, PCI or coronary artery bypass graft, SYNTAX or J-CTO scores, and CTO-related artery percentages) did not suggest any statistically significant relationships. Conclusions: CTO PCI appears to have a similar efficacy profile compared to no intervention at long-term follow-up, but with a significant improvement of angina favoring PCI-treated patients. Further adequately powered and long-term trials are required to identify the best management strategy for patients with coronary CTO. [ABSTRACT FROM AUTHOR]

Aims Remote ischaemic conditioning (RIC) has been shown to reduce myocardial infarct size in animal models of myocardial infarction. Platelet thrombus formation is a critical determinant of outcome in ST-segment elevation myocardial infarction (STEMI). Whether the beneficial effects of RIC are related to thrombotic parameters is unclear. Methods and results In a substudy of the Effect of Remote Ischaemic Conditioning on clinical outcomes in STEMI patients undergoing Primary Percutaneous Coronary Intervention (ERIC-PPCI) trial, we assessed the effect of RIC on thrombotic status. Patients presenting with STEMI were randomized to immediate RIC consisting of an automated autoRIC™ cuff on the upper arm inflated to 200 mmHg for 5 min and deflated for 5 min for four cycles (n  = 53) or sham (n  = 47). Venous blood was tested at presentation, discharge (48 h) and 6–8 weeks, to assess platelet reactivity, coagulation, and endogenous fibrinolysis using the Global Thrombosis Test and thromboelastography. Baseline thrombotic status was similar in the two groups. At discharge, there was some evidence that the time to in vitro thrombotic occlusion under high shear stress was longer with RIC compared to sham (454 ± 105 s vs. 403 ± 105 s; mean difference 50.1 s; 95% confidence interval 93.7–6.4, P  = 0.025), but this was no longer apparent at 6–8 weeks. There was no difference in clot formation or endogenous fibrinolysis between the study arms at any time point. Conclusion RIC may reduce platelet reactivity in the first 48 h post-STEMI. Further research is needed to delineate mechanisms through which RIC may reduce platelet reactivity, and whether it may improve outcomes in patients with persistent high on-treatment platelet reactivity. [ABSTRACT FROM AUTHOR]

Aims The endogenous fibrinolytic system serves to prevent lasting thrombotic occlusion and infarction following initiation of coronary thrombosis. We aimed to determine whether impaired endogenous fibrinolysis can identify patients with ST-segment elevation myocardial infarction (STEMI) who remain at high cardiovascular risk despite dual antiplatelet therapy (DAPT). Methods and results A prospective, observational study was conducted in 496 patients presenting with STEMI for primary percutaneous coronary intervention (PPCI). Blood was tested on arrival pre-PPCI, at discharge and at 30 days to assess thrombotic status using the automated point-of-care global thrombosis test and patients followed for 1 year for major adverse cardiovascular events (MACEs). Endogenous fibrinolysis was significantly impaired [baseline lysis time (LT) ≥2500 s] in 14% of patients and was highly predictive of recurrent MACE [hazard ratio (HR) 9.1, 95% confidence interval (CI) 5.29–15.75; P  < 0.001], driven by cardiovascular death (HR 18.5, 95% CI 7.69–44.31; P  < 0.001) and myocardial infarction (HR 6.2, 95% CI 2.64–14.73; P  < 0.001), particularly within 30 days. Fibrinolysis remained strongly predictive of MACE after adjustment for conventional risk factors (HR 8.03, 95% CI 4.28–15.03; P  < 0.001). Net reclassification showed that adding impaired fibrinolysis improved the prediction of recurrent MACE by >50% (P  < 0.001). Patients with spontaneous ST-segment resolution pre-PPCI had more rapid, effective fibrinolysis [LT 1050 (1004–1125) s vs. 1501 (1239–1997) s, P  < 0.001] than those without. Lysis time was not altered by standard of care STEMI treatment including DAPT and was unchanged at 30 days. Conclusion Endogenous fibrinolysis assessment can identify patients with STEMI who remain at very high cardiovascular risk despite PPCI and DAPT. Further studies are needed to assess whether these patients may benefit from additional, personalized antithrombotic/anticoagulant medication to reduce future cardiovascular risk. Clinical trial registration http://www.clinicaltrials.gov. Unique identifier: NCT02562690. View large Download slide View large Download slide [ABSTRACT FROM AUTHOR]

Aims: Approximately 20% of ischaemic stroke patients exhibit spontaneous arterial recanalization, attributable to endogenous fibrinolysis, which strongly relates to improved functional outcome. The impact of oral anticoagulants on endogenous fibrinolysis is unknown. Our aim was to test the hypothesis that apixaban enhances endogenous fibrinolysis in non-valvular atrial fibrillation (NVAF)., Methods and Results: In a prospective cross-sectional analysis, we compared endogenous fibrinolysis in NVAF patients (n = 180) taking aspirin, warfarin, or apixaban. In a prospective longitudinal study, patients were tested before and after apixaban (n = 80). Endogenous fibrinolysis was assessed using the Global Thrombosis Test (GTT) and thromboelastography (TEG). Endogenous fibrinolysis [measured by GTT lysis time (LT)] was shorter on apixaban compared with warfarin or aspirin [median 1850 (IQR 1591-2300) vs. 2758 (2014-3502) vs. 2135 (1752-2463) s, P < 0.0001]. Among TEG indices, a small but significant difference in clot lysis time (CLT) was observed [apixaban 60.0 (45.0-61.0) vs. warfarin 61.0 (57.0-62.0) vs. aspirin 61.0 (59.0-61.0) min, P = 0.036]. Apixaban improved endogenous fibrinolysis measured using the GTT [LT pre-treatment 2204 (1779-2738) vs. on-treatment 1882 (1607-2374) s, P = 0.0003], but not by using TEG. Change in LT (ΔLT) with apixaban correlated with baseline LT (r = 0.77, P < 0.0001). There was weak correlation between ΔLT and ΔCLT in response to apixaban (r = 0.28, P = 0.02) and between on-apixaban LT and CLT (r = 0.25, P = 0.022)., Conclusion: Apixaban enhances endogenous fibrinolysis, with maximal effect in those with impaired fibrinolysis pre-treatment. Apixaban-treated patients exhibit more favourable fibrinolysis profiles than those taking warfarin or aspirin. Whether apixaban may confer additional thrombotic risk reduction in NVAF patients with impaired fibrinolysis, compared to warfarin, merits further study., (© The Author(s) 2019. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Although used routinely to reduce thrombotic events in patients with coronary disease, the effects of P2Y 12 inhibitors on thrombus stability and endogenous fibrinolysis are largely unknown. Blood taken from patients pre- and post-aspirin (n = 20) and on aspirin alone and on dual antiplatelet therapy comprising aspirin plus clopidogrel (n = 20), ticagrelor (n = 20) or cangrelor (n = 20), was tested using the Global Thrombosis Test. The number of "rebleeds" or drops (D) after early platelet-rich thrombus formation (occlusion time, OT), and before final lasting occlusion, was used as an inverse measure of thrombus stability. Whilst clopidogrel had no effect, ticagrelor and cangrelor both increased D significantly, reflecting increased thrombus instability [D pre- and post-clopidogrel 4.3 ± 1.6 vs. 4.5 ± 1.4, p = 0.833; pre- and post-ticagrelor 4.1 ± 2.4 vs. 6.8 ± 5.1, p = 0.048; pre- and post-cangrelor 3.6 ± 2.0 vs. 7.9 ± 8.9, p = 0.046]. Platelet reactivity was reduced by all P2Y 12 inhibitors, demonstrated by OT prolongation (clopidogrel 378 ± 87 s vs. 491 ± 93 s, p < 0.001; ticagrelor 416 ± 122 s vs. 549 ± 121 s, p < 0.001; cangrelor 381 ± 146 s vs. 613 ± 210 s, p < 0.001). The magnitude of OT prolongation compared to baseline (ΔOT) was significantly greater for cangrelor compared to clopidogrel and ticagrelor. Cangrelor was the only agent to enhance fibrinolysis (lysis time pre- and post-cangrelor 1622[1240-2048]s vs. 1388[960-1634]s, p = 0.005). We demonstrate the ability to assess the effect of pharmacotherapy on thrombus stability in vitro and show that P2Y 12 inhibitors potentiate thrombus instability at high shear. Cangrelor, and to a lesser extent ticagrelor, de-stabilised thrombus formation and cangrelor also enhanced fibrinolysis. Potentiation of thrombus instability could become a new pharmacological target, that may be particularly important in acute coronary syndromes., (Copyright © 2018 Elsevier Ltd. All rights reserved.)