Catholic University of the Sacred Heart, Rome, Italy.
Maria Cecilia Hospital, GVM Care & Research, Cotignola, Italy.
Expert Rev Clin Pharmacol. 2023 Jan;16(1):27-38. doi: 10.1080/17512433.2023.2154651. Epub 2022 Dec 12.
The persistence of elevated rates of ischemic recurrences despite the use of antiplatelet therapy among patients with atherosclerotic disease together with the understanding of the pivotal role of coagulation in the thrombo-inflammatory processes involved in the pathogenesis of atherosclerosis and its complications has fostered the development of treatments targeting both platelets and coagulation, a strategy known as dual-pathway inhibition (DPI).
In this review we discuss the recent advancements in the understanding of the interplay between coagulation, platelets and inflammation involved in the pathophysiology of atherosclerosis and atherothrombosis, as the rationale for the implementation of a DPI strategy. We also discuss the available pharmacodynamic (PD) evidence and clinical implications with the use of DPI in patients with atherosclerotic disease.
The implementation of a DPI by adding the so-called 'vascular dose of rivaroxaban' (i.e. 2.5 mg bis in die), on top of antiplatelet therapy has consistently been associated with reduced levels of thrombin generation in PD studies and with reduced ischemic event rates at the cost of increased bleeding compared to antiplatelet therapy alone. Further research is warranted to best define patients in whom a DPI regimen has the best safety and efficacy profile.
尽管在动脉粥样硬化疾病患者中使用抗血小板治疗，但仍存在缺血性复发率升高的情况，同时对凝血在涉及动脉粥样硬化及其并发症发病机制的血栓炎症过程中的关键作用的理解，促进了针对血小板和凝血的双重途径抑制（DPI）治疗方法的发展。
在这篇综述中，我们讨论了对凝血、血小板和炎症之间相互作用的最新认识，这些相互作用涉及动脉粥样硬化和动脉血栓形成的病理生理学，这是实施 DPI 策略的理论基础。我们还讨论了在动脉粥样硬化疾病患者中使用 DPI 的现有药效学（PD）证据和临床意义。
在 PD 研究中，与单独使用抗血小板治疗相比，在抗血小板治疗的基础上添加所谓的“血管剂量利伐沙班”（即每天两次 2.5 毫克），实施 DPI 一直与凝血酶生成水平降低以及缺血性事件发生率降低相关，但出血风险增加。需要进一步的研究来最好地确定哪些患者使用 DPI 方案具有最佳的安全性和疗效。
