Among patients with NSTE acute coronary syndromes who were scheduled to undergo catheterization, pretreatment with prasugrel did not reduce the rate of major ischemic events up to 30 days but increased the rate of major bleeding complications. (Funded by Daiichi Sankyo and Eli Lilly; ACCOAST ClinicalTrials.gov number, NCT01015287.).

No abstract

No abstract

Increasing airflow obstruction and hypercapnia are associated with an enhanced TNFalpha response in COPD.

The synthetic direct thrombin inhibitor argatroban has a rapid onset and offset of anticoagulation. However, there are no data about the pharmacokinetic-pharmacodynamic (PK-PD) relationship of argatroban in patients undergoing contemporary percutaneous coronary intervention (PCI) and no data about other coagulation parameters than activated clotting time (ACT) in this setting. In the ARG-E04-trial, 140 patients were randomly assigned to argatroban (250, 300, or 350 µg/kg as bolus before PCI, followed by 15, 20, or 25 µg/kg/min infusion) or unfractionated heparin (70-100 IU/kg bolus). A 2-compartment model with first-order elimination adequately described the pharmacokinetic profile of argatroban over all 3 dosing groups. Clearance (CL) and distribution volumes (V1 and V2) were 21 L/h, 9.2 L, and 6.6 L, respectively. A significant sigmoidal E(max) relationship was established between the argatroban plasma concentration and the response in ACT and the endogenous thrombin potential (ETP), whereas the response in activated partial thromoplastin time (aPTT), ecarin time (ECA-T), and prothrombinase-induced clotting time (PiCT) could be described by a nonsigmoidal E(max) model. This study proves a relatively small interindividual variability of both PK and PK-PD properties of argatroban even at high doses and supports the profile of argatroban as a drug with a predictive dose-effect relationship and therefore good controllability.

Background: Time-to-first-event analysis considers only the first event irrespective of its severity. There are several methods to assess trial outcomes beyond time-to-first-event analysis, such as analyzing total events and ranking outcomes. In the GLOBAL LEADERS study, time-to-first-event analysis did not show superiority of ticagrelor monotherapy following one-month dual antiplatelet therapy (DAPT) after percutaneous coronary intervention to conventional 12-month DAPT followed by aspirin monotherapy in the reduction of the primary composite end point of all-cause mortality or new Q-wave myocardial infarction. This study sought to explore various analytical approaches in assessing total ischemic and bleeding events after percutaneous coronary intervention in the GLOBAL LEADERS study. Methods and Results: Total ischemic and bleeding events were defined as all-cause mortality, any stroke, any myocardial infarction, any revascularization, or Bleeding Academic Research Consortium grade 2 or 3 bleeding. We used various analytical approaches to analyze the benefit of ticagrelor monotherapy over conventional DAPT. For ischemic and bleeding events at 2 years after percutaneous coronary intervention, ticagrelor monotherapy demonstrated a 6% risk reduction, compared with conventional 12-month DAPT in time-to-first-event analysis (hazard ratio, 0.94 [95% CI, 0.88–1.01]; log-rank P =0.10). In win ratio analysis, win ratio was 1.05 (95% CI, 0.97–1.13; P =0.20). Negative binomial regression and Andersen-Gill analyses which include repeated events showed statistically significant advantage for ticagrelor monotherapy (rate ratio, 0.92 [95% CI, 0.85–0.99; P =0.020] and hazard ratio, 0.92 [95% CI, 0.85–0.99; P =0.028], respectively), although in weighted composite end point analysis, the hazard ratio was 0.93 (95% CI, 0.84–1.04; log-rank P =0.22). Conclusions: Statistical analyses considering repeated events or event severity showed that ticagrelor monotherapy consistently reduced ischemic and bleeding events by 5% to 8%, compared with conventional 1-year DAPT. Applying multiple statistical methods could emphasize the multiple facets of a trial and result in accurate and more appropriate analyses. Considering the recurrence of ischemic and bleeding events, ticagrelor monotherapy appeared to be beneficial after percutaneous coronary intervention. Registration: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT01813435.

CME-Fortbildung Dieses Dokument wurde zum persönlichen Gebrauch heruntergeladen. Vervielfältigung nur mit Zustimmung des Verlages.

ZusammenfassungIn dieser Übersicht stellen wir die aktuelle Literatur zum Gerinnungsmanagement nach TAVI zusammen. Aus den publizierten Studien ergibt sich für die klinische Praxis, dass direkte orale Antikoagulanzien den Vitamin-K-Antagonisten nicht unterlegen sind, wenn aus anderen Gründen (z. B. Vorhofflimmern) eine Antikoagulation nach TAVI erforderlich ist. Die zusätzliche Gabe eines Thrombozytenaggregationshemmers bringt in dieser Konstellation keinen Vorteil. Bei Patienten, die keine Indikation für eine orale Antikoagulation haben, hat sich in vielen Zentren die duale Thrombozytenaggregationshemmung mit ASS und Clopidogrel für 3–6 Monate als Standard etabliert. Die randomisierte POPular TAVI-Studie hat allerdings gezeigt, dass die alleinige ASS-Gabe nach TAVI Blutungskomplikationen reduziert, bei gleicher Sicherheit in der Verhinderung thrombotischer Komplikationen.