Thrombosis and haemostasis
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Randomized Controlled Trial
A randomised study for optimising crossover from ticagrelor to clopidogrel in patients with acute coronary syndrome. The CAPITAL OPTI-CROSS Study.
Ticagrelor has been endorsed by guidelines as the P2Y12 inhibitor of choice in patients with acute coronary syndrome. Clinically, some patients on ticagrelor will require a switch to clopidogrel; however, the optimal strategy and pharmacodynamics effects of switching remain unknown. Patients with an indication to switch were randomly assigned to either a bolus arm (Clopidogrel 600 mg bolus followed by 75 mg daily, n=30) or a no-bolus arm (Clopidogrel 75 mg daily, n=30). ⋯ Although a bolus strategy was not associated with improved platelet inhibition at 72 h; at 48 h, platelet inhibition was superior with reduced incidence of HPR. Larger studies will be required to determine its clinical significance. Until then, decision for giving a bolus of clopidogrel at the time of a switch may in part be dependent on the indication for switching, especially if there are concerns for bleeding risk.
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Multicenter Study
Clinical evaluation of glycoPEGylated recombinant FVIII: Efficacy and safety in severe haemophilia A.
Turoctocog alfa pegol (N8-GP) is a novel glycoPEGylated extended half-life recombinant factor VIII (FVIII) product developed for prophylaxis and treatment of bleeds in patients with haemophilia A, to enable higher activity levels with less frequent injections compared with standard FVIII products. This phase III (NCT01480180), multinational, open-label, non-randomised trial evaluated the safety and clinical efficacy of N8-GP when administered for treatment of bleeds and for prophylaxis, in previously treated patients aged ≥12 years with severe haemophilia A. Patients were allocated to receive N8-GP for prophylaxis or on-demand treatment for up to 1.8 years. ⋯ The frequency and types of adverse events reported were as expected in this population. One patient developed inhibitory antibodies against FVIII (≥0.6 Bethesda units [BU]) after 93 N8-GP exposure days. No clinically significant safety concerns were identified and N8-GP was effective for prophylaxis and treatment of bleeds in previously treated patients.
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Reasons for trends in venous thromboembolism (VTE) incidence are uncertain. It was our objective to determine VTE incidence trends and risk factor prevalence, and estimate population-attributable risk (PAR) trends for each risk factor. In a population-based cohort study of all residents of Olmsted County, Minnesota from 1981-2010, annual incidence rates were calculated using incident VTE cases as the numerator and age- and sex-specific Olmsted County population estimates as the denominator. ⋯ The PAR of active cancer and surgery, 1981-2010, significantly increased. In conclusion, almost 80 % of incident VTE events are attributable to known major VTE risk factors and one-third of incident idiopathic VTE events are attributable to obesity. Increasing surgery PAR suggests that concurrent efforts to prevent VTE may have been insufficient.
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Observational Study
Real-life treatment of venous thromboembolism with direct oral anticoagulants: The influence of recommended dosing and regimens.
In patients with venous thromboembolism (VTE), the influence on outcome of using direct oral anticoagulants (DOACs) at non-recommended doses or regimens (once vs twice daily) has not been investigated yet. We used the RIETE (Registro Informatizado Enfermedad TromboEmbólica) registry to compare the outcomes in patients with VTE receiving DOACs according to the recommendations of the product label versus in those receiving non-recommended doses and/or regimens. The major outcomes were the rate of VTE recurrences, major bleeding and death during the course of therapy. ⋯ Patients receiving DOACs at non-recommended doses and/or regimens experienced a higher rate of VTE recurrences (adjusted HR: 10.5; 95 %CI: 1.28-85.9) and a similar rate of major bleeding (adjusted HR: 1.04; 95 %CI: 0.36-3.03) or death (adjusted HR: 1.41; 95 %CI: 0.46-4.29) than those receiving the recommended doses and regimens. In our cohort, a non-negligible proportion of VTE patients received non-recommended doses and/or regimens of DOACs. This use may be associated with worse outcomes.
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Both type 2 diabetes (T2DM) and Bβ448Lys variant of fibrinogen are associated with dense fibrin clots, impaired fibrinolysis and increased cardiovascular risk. It was our objective to investigate whether BβArg448Lys adds to vascular risk by modulating fibrin network structure and/or fibrinolysis in diabetes. The primary aim was to study effects of BβArg448Lys on fibrin network characteristics in T2DM. ⋯ Women with Bβ448Lys genotype had increased risk of cerebrovascular events and were younger compared with Bβ448Arg variant (67.2 ± 4.0 and 68.2 ± 4.4 years, respectively; p=0.035). In conclusion, fibrinogen Bβ448Lys variant is associated with thrombotic fibrin clots in diabetes independently of traditional risk factors. Prospective studies are warranted to fully understand the role of BβArg448Lys in predisposition to vascular ischaemia in T2DM with the potential to develop individualised antithrombotic management strategies.