Thrombosis and haemostasis
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Review Comparative Study
Comparative efficacy and safety of the novel oral anticoagulants dabigatran, rivaroxaban and apixaban in preclinical and clinical development.
Therapeutic oral anticoagulation is still commonly achieved by administration of warfarin or other vitamin K antagonists that are associated with an untoward pharmacokinetic / pharmacodynamic (PK/PD) profile leading to a high incidence of bleeding complications or therapeutic failure. Hence, there is an unmet medical need of novel easy-to-use oral anticoagulants with improved efficacy and safety. Recent developments include the identification of non-peptidic small-molecules that selectively inhibit certain serine proteases within the coagulation cascade. ⋯ Phase III trials in orthopaedic patients essentially resulted in non-inferior efficacy of dabigatran and superior efficacy of rivaroxaban over enoxaparin without any marked differences of drug safety, while apixaban data is still controversial. However, alterations of rivaroxaban and apixaban pharmacokinetics upon interactions with inhibitors and inducers of CYP3A4 or P-glycoprotein may complicate the use of these compounds in daily practice, whereas dabigatran elimination largely depends on renal function. Hence, this review reports PK/PD, efficacy and safety data of dabigatran, rivaroxaban and apixaban throughout preclinical and clinical development.
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The in-hospital incidence of pulmonary embolism (PE) in patients undergoing elective joint arthroplasty who receive a minimum of 10 days of dalteparin prophylaxis is reported to be less than 1%. Recent clinical experience raised suspicion that the incidence of PE was significantly higher at our tertiary care institution. It was the objective of this study to determine the incidence of in-hospital PE and symptomatic deep-vein thrombosis following elective joint arthroplasty in patients who received a minimum of 10 days of dalteparin prophylaxis. ⋯ The incidence of in-hospital PE in knee arthroplasty patients who received dalteparin prophylaxis was significantly higher than expected. Potential explanations for this finding include poor efficacy of dalteparin started 12-24 hours postoperatively and/or a low threshold for ordering diagnostic imaging for PE. Studies to clarify these issues are needed.
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Multicenter Study Clinical Trial
Clopidogrel response status assessed with Multiplate point-of-care analysis and the incidence and timing of stent thrombosis over six months following coronary stenting.
Clopidogrel low-responsiveness assessed with multiple electrode platelet aggregometry (MEA) has been shown to be a strong and independent predictor of early stent thrombosis (ST) after coronary stenting. The relation of clopidogrel response status, as assessed with MEA, with incidence and timing of ST during an extended follow-up period has never been reported. Here, we report the six-month follow-up results of a prospective trial assessing clopidogrel responsiveness with MEA in patients undergoing percutaneous coronary intervention (PCI). ⋯ A significant inverse correlation of MEA values and the timing of definite or probable ST (in days) was observed (Spearman coefficient = -0.45; P=0.04) with events occurring earlier in the low-responder group. MEA measurements are highly predictive for the occurrence of ST during the first six months following coronary stenting. In the majority of clopidogrel low responders suffering ST, the ischaemic event occurs early in the course after the procedure.