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Abstract-Intravenous infusion of recombinant tissue factor pathway inhibitor (rTFPI) for 24 hours decreases neointimal thickening and luminal stenosis 1 month after balloon-induced injury to the carotid arteries in minipigs. This study was designed to determine whether the effect of rTFPI is accounted for by early decreases in procoagulant activity and thrombosis on the injured vessel wall. Vascular injury was induced by balloon hyperinflations in both carotid arteries of anesthetized pigs given no anticoagulant as a control (nϭ16), an intravenous infusion for 24 hours of rTFPI (0.5 mg/kg bolus and 25 g ⅐ kg Ϫ1 ⅐ min Ϫ1 , nϭ14), or an intravenous infusion of unfractionated heparin (100 U ⅐ kg Ϫ1 ⅐ h Ϫ1 , nϭ19). Accumulation of radiolabeled autologous platelets was markedly decreased over 24 hours on injured arteries from animals given rTFPI (0.6ϫ10 6 /cm 2 ) compared with controls (2.5ϫ10 6 /cm 2 , Pϭ0.0004). Deposition of radiolabeled fibrin was also decreased in rTFPI-treated animals (269Ϯ266 g/cm 2 ) compared with controls (2389Ϯ1673 g/cm 2 , Pϭ0.04). Similar effects were observed with heparin. However, factor Xa activity, assayed after 24 hours by incubation of the injured arterial segments with the chromogenic substrate S-2222, was decreased more markedly on arteries from rTFPI-treated animals (0.14Ϯ0.13 OD) than those from heparin-treated animals (0.29Ϯ0.18 OD) compared with controls (0.47Ϯ0.24 OD, Pϭ0.0007). In addition, arteries from rTFPI-treated animals showed a 4-fold lower induction of tissue factor protein compared with controls (Pϭ0.0002). Attenuation of procoagulant activity and tissue factor-mediated thrombin generation in response to injury may account for the promising results with rTFPI in the porcine angioplasty model.

There is a growing appreciation for differences in epidemiology, treatment, and outcomes of cardiovascular conditions by sex. Historically, cardiovascular clinical trials have under-represented females, but findings have nonetheless been applied to clinical care in a sex-agnostic manner. Thus, much of the collective knowledge about sex-specific cardiovascular outcomes result from post hoc and secondary analyses. In some cases, these investigations have revealed important sex-based differences with implications for optimizing care for female patients with arrhythmias. This review explores the available evidence related to cardiac arrhythmia care among females, with emphasis on areas in which important sex differences are known or suggested. Considerations related to improving female enrollment in clinical trials as a way to establish more robust clinical evidence for the treatment of females are discussed. Areas of remaining evidence gaps are provided, and recommendations for areas of future research and specific action items are suggested. The overarching goal is to improve appreciation for sex-based differences in cardiac arrhythmia care as 1 component of a comprehensive plan to optimize arrhythmia care for all patients.