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Halvorsen S.,University of Oslo | Huber K.,Wilhelminenhospital
Hamostaseologie | Year: 2014

Primary percutaneous coronary intervention (PPCI) is the preferred reperfusion therapy in ST-elevation myocardial infarction (STEMI), as long as it can be delivered within 90-120 minutes from patient's first medical contact, and is the leading reperfusion strategy in most European countries. However, as PPCI cannot be offered in a timely manner to all patients, fibrinolytic therapy (FT) is the recommended choice in patients with an anticipated delay to PPCI of >90-120 minutes, presenting early after symptom onset and without contra-indications. FT should preferably be started in the pre-hospital setting. Following FT, all patients should be transferred to a PCI-center for rescue PCI or routine coronary angiography with PCI as indicated. Such a pharmaco-invasive strategy, combining FT with invasive treatment, has recently been shown to be non-inferior to PPCI in patients living in areas with long transfer delays to PCI (>60 minutes). In this overview, we will briefly present the evidence for the benefit of FT in STEMI, and discuss the role of FT in the current era of PPCI as well as the optimal treatment following pharmacologic reperfusion. © Schattauer 2014.

Rega-Kaun G.,Medical University of Vienna | Rega-Kaun G.,Wilhelminenhospital | Kaun C.,Medical University of Vienna | Wojta J.,Medical University of Vienna | Wojta J.,Ludwig Boltzmann Cluster for Cardiovascular Research
Thrombosis and Haemostasis | Year: 2013

Overweight and obesity in many countries have developed into a serious health problem by themselves and by their impact on other pathologies such as insulin resistance, type 2 diabetes, hypertension, heart disease and cancer. The modulation of these diseases by adipose tissue-derived biomolecules, so-called adipokines, could be the key to differentiate between metabolically healthy and unhealthy obesity This review will discuss the pathophysiological role of selected adipokines, primarily focusing on cardiovascular diseases. Furthermore, we. will highlight possible therapeutic approaches, which target these bio-molecules. © Schattauer 2013.

Siller-Matula J.M.,Medical University of Vienna | Trenk D.,Universitaets Herzzentrum Freiburg Bad Krozingen | Schror K.,Heinrich Heine University Düsseldorf | Gawaz M.,University of Tübingen | And 3 more authors.
Thrombosis and Haemostasis | Year: 2015

Within the past decade, high on-treatment platelet reactivity (HTPR) on clopidogrel and its clinical implications have been frequently discussed. Although it has been previously assumed that HTPR is a phenomenon occurring only in patients treated with clopidogrel, recent data show that HTPR might also occur during treatment with prasugrel or ticagrelor in the acute phase of ST-elevation myocardial infarction. Moreover, it has been postulated that there is a therapeutic window for P2Y12 receptor blockers, thus indicating that HTPR is associated with thrombotic events whereas low on-treatment platelet reactivity (LTPR) is associated with bleeding events. The current paper focuses on tools to identify risk factors for HTPR (pharmacogenomic testing, clinical scoring and drug-drug interactions) and on the use of platelet function testing in order to identify patients who might not respond adequately to clopidogrel. The majority of recent clinical randomised trials have not supported the hypothesis that platelet function testing and tailored antiplatelet therapy are providing a favourable clinical outcome. These trials, mainly performed in low-to-moderate risk patients, will be reviewed and discussed. Finally, an algorithm based on current knowledge is suggested, which might be of use for design of clinical trials. © Schattauer 2015.

Kristensen S.D.,Aarhus University Hospital | Wurtz M.,Aarhus University Hospital | Grove E.L.,Aarhus University Hospital | de Caterina R.,University of Chieti Pescara | And 3 more authors.
Thrombosis and Haemostasis | Year: 2012

Platelet glycoprotein IIb/IIIa inhibitors (GPI) are antithrombotic agents preventing the binding of fibrinogen to GP IIb/IIIa receptors. Thus, GPI interfere with interplatelet bridging mediated by fibrinogen. Currently, three generic GPI with different antithrombotic properties are available for intravenous administration: abciximab, eptifibatide, and tirofiban. The development of oral GPI was abandoned, whereas intravenous GPI were introduced in various clinical settings during the 1990s, yielding substantial benefit in the treatment of acute coronary syndromes, particularly during percutaneous coronary interventions. Results of the many randomised trials evidenced the efficacy of this drug class, though these trials were conducted prior to the emergence of modern oral antiplatelet therapy with efficient P2Y 12 inhibitors. Subsequent trials failed to consolidate the strongly favourable impression of GPI, and indications for their use have been more restricted in recent years. Nonetheless, GPI may still be beneficial during coronary interventions among high-risk patients including acute ST-elevation and non-ST-elevation myocardial infarctions, particularly in the absence of adequate pretreatment with oral antiplatelet drugs or when direct thrombin inhibitors are not utilised. Intracoronary GPI administration has been suggested as adjunctive therapy during primary percutaneous coronary intervention, and the results of larger ongoing trials are expected to elucidate its clinical potential. The present review outlines the key milestones of GPI development and provides an up-to-date overview of the clinical applicability of these drugs in the era of refined coronary stenting, potent antithrombotic drugs, and novel thrombin inhibiting agents. © Schattauer 2012.

Siller-Matula J.M.,Medical University of Vienna | Jilma B.,Medical University of Vienna | Schror K.,Heinrich Heine University Düsseldorf | Christ G.,Kaiser Franz Joseph Hospital | Huber K.,Wilhelminenhospital
Journal of Thrombosis and Haemostasis | Year: 2010

To investigate whether proton pump inhibitors (PPIs) negatively affect clinical outcome in patients treated with clopidogrel. Systematic review and meta-analysis. Outcomes evaluated were combined major adverse cardiac events (MACE), myocardial infarction (MI), stent thrombosis, death and gastrointestinal bleeding. Studies included were randomized trials or post-hoc analyzes of randomized trials and observational studies reporting adjusted effect estimates. Twenty five studies met the selection criteria and included 159-138 patients. Administration of PPIs together with clopidogrel corresponded to a 29% increased risk of combined major cardiovascular events [risk ratio (RR)-=-1.29, 95% confidence intervals (CI)-=-1.15-1.45] and a 31% increased risk of MI (RR-=-1.31, 95%CI-=-1.12-1.53). In contrast, PPI use did not negatively influence the mortality (RR-=-1.04, 95%CI-=-0.93-1.16), whereas the risk of developing a gastrointestinal bleed under PPI treatment decreased by 50% (RR-=-0.50, 95% CI-=-0.37-0.69). The presence of significant heterogeneity might indicate that the evidence is biased, confounded or inconsistent. The sensitivity analysis, however, yielded that the direction of the effect remained unchanged irrespective of the publication type, study quality, study size or risk of developing an event. Two studies indicate that PPIs have a negative effect irrespective of clopidogrel exposure. In conclusion, concomitant PPI use might be associated with an increased risk of cardiovascular events but does not influence the risk of death. Prospective randomized trials are required to investigate whether a cause-and-effect relationship truly exists and to explore whether different PPIs worsen clinical outcome in clopidogrel treated patients as the PPI-clopidogrel drug-drug interaction does not seem to be a class effect. © 2010 International Society on Thrombosis and Haemostasis.

Siller-Matula J.M.,Medical University of Vienna | Trenk D.,Universitats Herzzentrum Freiburg Bad Krozingen | Schror K.,Heinrich Heine University Düsseldorf | Gawaz M.,University of Tübingen | And 3 more authors.
JACC: Cardiovascular Interventions | Year: 2013

P2Y12 inhibitors are widely used in patients with acute coronary syndromes and in the secondary prevention of thrombotic events in vascular diseases. Within the past few years, several pharmacological, genetic, and clinical limitations of the second-generation thienopyridine clopidogrel have raised major concerns. High on-treatment platelet reactivity, which is common in clopidogrel-treated patients, and its clinical implications led to the development of the more effective platelet P2Y12 inhibitors prasugrel (a third-generation thienopyridine) and ticagrelor (a cyclopentyl-triazolo- pyrimidine). The pharmacokinetics and pharmacodynamics of prasugrel and ticagrelor indicate that they provide more consistent, more rapid, and more potent platelet inhibition than clopidogrel, which translates into improved ischemic outcomes. Nevertheless, higher efficacy, which is reflected by low on-treatment platelet reactivity, increases the risk of major bleeding events. Therefore, cardiologists might be facing a new challenge in the future: to individualize the level of platelet inhibition in order to decrease thrombotic events without increasing bleeding. The current review focuses on the use of platelet function testing and pharmacogenomic testing in order to identify patients who either do not respond to or are at risk of not responding sufficiently to P2Y12 inhibitors. Moreover, this paper discusses randomized trials, which so far have failed to show that tailored antiplatelet therapy improves clinical outcome, and treatment options for patients with high on-treatment platelet reactivity. © 2013 BY THE AMERICAN COLLEGE OF CARDIOLOGY FOUNDATION PUBLISHED BY ELSEVIER INC.

Siller-Matula J.M.,Medical University of Vienna | Christ G.,Kaiser Franz Josef Hospital | Lang I.M.,Medical University of Vienna | Delle-Karth G.,Medical University of Vienna | And 2 more authors.
Journal of Thrombosis and Haemostasis | Year: 2010

Background and Aim: The prognostic value of the vasodilator-stimulated phosphoprotein (VASP) phosphorylation assay and multiple electrode aggregometry (MEA) for thrombotic adverse events has been shown in independent studies. As no direct comparison between the two methods has been made so far, we investigated which laboratory approach has a better predictive value for stent thrombosis. Methods: The VASP phosphorylation assay and MEA were performed in 416 patients with coronary artery disease undergoing percutaneous coronary intervention. The rate of stent thrombosis was recorded during a 6-month follow-up. Results: Definite stent thrombosis occurred in three patients (0.7%) and probable stent thrombosis in four (1%). Receiver operating characteristic (ROC) analysis demonstrated that MEA distinguishes between patients with or without subsequent stent thrombosis better than the VASP phosphorylation assay: the area under the ROC curve was higher for MEA (0.92; P = 0.012) than for the VASP phosphorylation assay (0.60; P = 0.55). At equal levels of sensitivity (100%), the specificity was greater for MEA than for the VASP phosphorylation assay (86% vs. 37%). Stent thrombosis occurred in 9% of patients with platelet hyperreactivity in MEA, who were simultaneously clopidogrel non-responders in the VASP phosphorylation assay. Interestingly, clopidogrel non-responders in the VASP phosphorylation assay without platelet hyperreactivity in MEA did not suffer from stent thrombosis. Conclusions: Platelet hyperreactivity in MEA might be a better risk predictor for stent thrombosis than the assessment of the specific clopidogrel effect with the VASP phosphorylation assay. © 2009 International Society on Thrombosis and Haemostasis.

Rohla M.,Wilhelminenhospital | Weiss T.W.,Wilhelminenhospital
Hamostaseologie | Year: 2013

Extensive research of the past decades altered our traditional concept about the genesis of atherosclerosis fundamentally. Today, the crucial role of inflammation in the formation and progression of atherosclerotic plaques is indisputable. Patients at high risk for developing cardiovascular disease, owing to poor diet, obesity and low physical activity have been shown to exhibit a particular inflammatory pattern. Therefore, the present review highlights the crosslink between the metabolic syndrome (MetS), adipose tissue, adipokines and selected inflammatory cytokines in the context of atherothrombosis and cardiovascular disease. © Schattauer 2013.

Huber K.,Wilhelminenhospital
European Heart Journal | Year: 2010

In their manuscript Harmsze et al.4 concluded that personalized therapy targeting patients who carry these genetic variants might help to improve clinical outcome after stent implantation. For the clinical role of genetic profiling multiple unknown factors still remain: while in the majority of trials CYP2C19 genetic polymorphisms and occasionally CYP2C9 genetic polymorphisms have been shown to reduce clopidogrel metabolism and its clinical effectiveness, there are no prospective studies demonstrating a clinical benefit of personalizing antiplatelet therapy based on genotyping. Commercially available genetic tests that can determine CYP2C19 genotype (and other) variants are not routinely reimbursed and point of care assays (e.g. for patients with ACS) are lacking at present. Moreover, it is important to point out that CYP2C19 polymorphisms account for only ∼12% of variability in clopidogrel platelet response,15 the positive predictive value of CYP2C19 loss-of-function polymorphisms for cardiovascular events in patients with ACS undergoing PCI is low, ∼12- 20%,8,15 and other clinical factors and risk constellations might be of greater clinical importance. Finally, it is not known whether a specific genetic polymorphism is capable of influencing outcome for the individual patient. Accordingly, genetic profiling should not be recommended for routine use at present but will remain of increased scientific interest. © 2010 The Author.

Schror K.,UniversitatsKlinikum Dusseldorf | Huber K.,Wilhelminenhospital
Thrombosis and Haemostasis | Year: 2015

Taken together, current evidence suggests that conventional antiplatelet drugs, such as aspirin, clopidogrel, prasugrel and ticagrelor also have antiinflammatory actions in different experimental settings and clinical conditions. These actions are thought to be primarily related to their antiplatelet effect. While there is significant evidence for aspirin-related antiinflammatory antiplatelet actions, the situation with ADP-antagonists is less clear, as it has been reported (28) that treatment with ticagrelor and clopidogrel did not lead to significant differences regarding the inflammatory biomarkers CRP, IL-6, and sCD40L in patients with NSTE-ACS among treatment groups at baseline, discharge, and at four weeks (23). However, these actions will be seen during DAPT and likely the anti - aggregatory effect might also be stronger with combined use. © Schattauer 2015.

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