Anti-inflammatory and antiplatelet effects of non-vitamin K antagonist oral anticoagulants in acute phase of ischemic stroke patients

Abstract

Background: Recently, non-vitamin K antagonist oral anticoagulants such as direct thrombin and direct factor Xa inhibitors have been prescribed for prevention of embolic stroke. While in Japan, argatroban, also a direct thrombin inhibitor, is available for the treatment of atherothrombotic stroke patients. This study aimed to explore whether there is any differences between direct thrombin and direct factor Xa inhibitors regarding the inhibiting effect against thrombogenesis in the clinical setting of acute ischemic stroke.

Methods: Acute ischemic stroke patients newly prescribed anti-thrombotic agents were consecutively screened, and 44 patients with single medicine were enrolled (median 72.0 years-old). Blood samples were obtained at 1 and 2 weeks after the medication started. The extent of anticoagulation activity, inflammatory markers and platelet aggregation were assessed. Patients with antiplatelets were used as control.

Results: Prescribed antithrombotics were dabigatran (group D: n = 12), apixaban (group A: n = 14) and antiplatelet agents (group P: n = 18). Prevalence of stroke risks and anticoagulation activity were not different between groups D and A. The alteration of inflammatory markers in a week in the group A showed similar trend to those in the group P. The group D presented relatively lower amount of high-sensitive C-reactive protein and higher amount of pentraxin-3 compared with groups A and P. While 88.9% of group P patients showed decreased platelet aggregation activity with adenosine diphosphate, 55.6% of group D and 40.0% of group A presented the inhibition of platelet aggregation activity.

Conclusions: Even in acute ischemic stroke patients, both apixaban and dabigatran equally showed the anticoagulation activity. The reduction of inflammatory response might be prominent in apixaban, whereas the inhibition of platelet aggregation activity might be evident in dabigatran.

Keywords: Blood platelets; Factor Xa; Inflammation; Stroke; Thrombin.

Fig. 1

The inclusion and exclusion criteria with number of patients

Fig. 2

The algorithm of selection of non-vitamin K antagonist oral anticoagulant (NOAC). This arm is used when a patient prefer a medicine twice a day administration. A patient with poor kidney function (CCr < 15 ml/min) cannot apply this algorithm. If a patient shows dysphagia, a NOAC which can be pulverized is considered for prescription. CCr creatinine clearance, BID twice a day oral administration

Fig. 3

Platelet aggregation activity elicited by ADP or collagen. The number of patients in whom platelet aggregation activity is reduced are increasing in 1 week in both groups D and A. This finding is observed in the same tendency as for elicitation by ADP and collagen. Bubble size and the number indicate the number of patients. Y axis expresses the degree of platelet coagulation activity. Negative number indicates reduced activity and positive number indicates accelerated activity