Dual Antithrombotic Therapy Increases Severe Bleeding Events in Patients With Stroke and Cardiovascular Disease

Abstract

Background and Purpose-We sought to determine the incidence and severity of bleeding events in patients with stroke and cardiovascular diseases who were taking oral antithrombotic agents in Japan, where the incidence of hemorrhagic stroke is higher than in Western countries. Methods-A prospective, multicenter, observational study was conducted; 4009 patients who were taking oral antithrombotic agents for stroke and cardiovascular diseases were enrolled. The patients were classified into 4 groups according to their antithrombotic treatment: the single antiplatelet agent group (47.2%); the dual antiplatelet agent group (8.7%); the warfarin group (32.4%); and the warfarin plus antiplatelet agent group (11.7%). The primary end point was life-threatening or major bleeding according to the MATCH trial definition. Results-During a median follow-up of 19 months, there were 57 life-threatening and 51 major bleeding events, including 31 intracranial hemorrhages. The annual incidence of the primary end point was 1.21% in the single antiplatelet agent group, 2.00% in the dual antiplatelet agent group, 2.06% in the warfarin group, and 3.56% in the warfarin plus antiplatelet agent group (PϽ0.001). After adjustment for baseline characteristics, adding an antiplatelet agent to warfarin increased the risk of the primary end point (relative riskϭ1.76; 95% CI, 1.05 to 2.95), and adding another antiplatelet agent to single antiplatelet agent therapy increased the secondary end point of any bleeding, including minor events (relative riskϭ1.37; 95% CI, 1.07 to 1.76). Conclusions-The incidence of bleeding events during antithrombotic therapy in Japan was similar to that reported for Western countries, although the trials used different study designs. Dual antithrombotic therapy was independently related to an increased risk of bleeding events.

Platelet Function Measured Using a Whole Blood Aggregometer Can Predict Bleeding Events

“…Subjects who took other combinations of medications (n 57), including 23 subjects who took various combinations of antiplatelet and anticoagulant agents, also had a relatively high number of bleeding events. These findings are consistent with the results of previous studies, which showed that the concomitant administration of antiplatelet and anticoagulant agents was associated with a relatively high risk of bleeding complications [28][29][30] . From the results of our study, however, we were unable to conclude that the combined use of antiplatelet and anticoagulant agents was an independent predictor of bleeding events.…”

Safety and Management of Antithrombotic Therapy with Intra-Arterial Catheter Procedures

“…Conversely, a single antiplatelet agent was the most common therapy in the cerebral angiography group, which included a large number of ischemic stroke patients. This is, however, an expected result, since multiple antiplatelet agents or the coadministration of antiplatelet agents and anticoagulants leads to an increase in intracranial bleeding and life-threatening severe bleeding in patients with a history of cerebrovascular disorders (9)(10)(11).…”

Retrospective Analysis of Delayed Intraparenchymal Hemorrhage after Flow-Diverter Treatment: Presentation of a Retrospective Multicenter Trial

“…29 Lately, antiplatelet treatment with hypertension has been associated with the occurrence of intracranial hemorrhages. 29 Even if hemorrhagic complications occur after stent placement, their incidence is low, about 2.2%; no intraparenchymal hemorrhage has been described remote from an aneurysm treated with stents. Therefore, the FD probably has a specific mechanism that may lead to intraparenchymal hemorrhage and that could be amplified by the antiplatelet regimen.…”