Standard vs Modified Antiplatelet Preparation for Preventing Thromboembolic Events in Patients With High On-Treatment Platelet Reactivity Undergoing Coil Embolization for an Unruptured Intracranial Aneurysm: A Randomized Clinical Trial.

IMPORTANCE: Thromboembolism is the most common complication in coiling for an unruptured aneurysm and is frequent in patients with high on-treatment platelet reactivity (HTPR) who are prescribed a standard antiplatelet preparation for its prevention. OBJECTIVE: To evaluate the effect of a modified antiplatelet preparation compared with a standard preparation in patients with HTPR undergoing coiling. DESIGN, SETTING, AND PARTICIPANTS: A prospective randomized open-label active-control trial with blinded outcome assessment at the Seoul National University Bundang Hospital from May 27, 2013, to April 7, 2014. Patients with HTPR were randomly assigned (1 to 1) to the standard or modified preparation group. Patients without HTPR were assigned to the non-HTPR group. A total of 228 patients undergoing coiling for unruptured aneurysms were enrolled and allocated to the study, 126 in the HTPR group (63 to the standard preparation group and 63 to the modified preparation group) and 102 to the non-HTPR group. Intent-to-treat analysis was performed. INTERVENTIONS: The modified preparation (HTPR to aspirin, 300 mg of aspirin and 75 mg of clopidogrel bisulfate; and HTPR to clopidogrel, 200 mg of cilostazol added to the standard regimen) was performed before coiling in the modified preparation group. Standard preparation (100 mg of aspirin and 75 mg of clopidogrel) was maintained in the standard preparation and non-HTPR groups. MAIN OUTCOMES AND MEASURES: The primary outcome was a thromboembolic event defined as thromboembolism during coiling and a transient ischemic attack or ischemic stroke within 7 days after coiling. The principal secondary outcome was a bleeding complication according to Thrombolysis in Myocardial Infarction bleeding criteria within 30 days after coil embolization. RESULTS: The thromboembolic event rate was low in the modified preparation group (1 of 63 [1.6%]) compared with the standard preparation group (7 of 63 [11.1%]; adjusted risk difference, -11.7% [95% CI, -21.3% to -2.0%]; P = .02), which had a higher thromboembolic risk than the non-HTPR group (1 of 102 [1.0%]; adjusted risk difference, 8.6% [95% CI, 1.0% to 16.3%]; P = .03). All bleeding complications were of minimal grade according to Thrombolysis in Myocardial Infarction bleeding criteria. The bleeding rate was not different between the modified (6 of 63 [9.5%]) and standard (4 of 63 [6.3%]) preparation groups (adjusted risk difference, 5.6% [95% CI, -4.2% to 15.4%]; P = .26). CONCLUSIONS AND RELEVANCE: Modified antiplatelet preparation for patients with HTPR compared with standard antiplatelet preparation reduced the thromboembolic event rate in coiling for an unruptured aneurysm without increasing bleeding. TRIAL REGISTRATION: Clinical Research Information Service Identifier: KCT0000804.

Delayed ischemic stroke after stent-assisted coil placement in cerebral aneurysm: characteristics and optimal duration of preventative dual antiplatelet therapy.

PURPOSE: To evaluate characteristics of delayed ischemic stroke after stent-assisted coil placement in cerebral aneurysms and to determine the optimal duration of dual antiplatelet therapy for its prevention. MATERIALS AND METHODS: This retrospective study was approved by the institutional review board, and the requirement to obtain written informed consent was waived. Of 1579 patients with 1661 aneurysms, 395 patients (25.0%) with 403 aneurysms (24.3%) treated with stent-assisted coil placement were included and assigned to groups stratified as early (126 patients [31.9%]; 3 months of coil placement), midterm (160 patients [40.5%]; 6 months), or late (109 patients [27.6%]; ≥ 9 months), according to the time points of switching dual antiplatelet therapy to monotherapy from coil placement. Cumulative rates of delayed ischemic stroke in each group were calculated by using Kaplan-Meier estimates that were compared with log-rank tests. Risk factors of delayed ischemic stroke were identified by using Cox proportional hazard analysis. RESULTS: Delayed ischemic stroke occurred in 3.5% of all cases (embolism, 3.0%; thrombotic occlusion, 0.5%) within 2 months following the switch. Late switch yielded no delayed ischemic stroke, unlike early (seven of 126 patients [5.6%]; P = .013) or midterm (seven of 160 patients [4.4%]; P = .028) switch. Incomplete occlusion (hazard ratio, 6.68 [95% confidence interval: 1.490, 29.900]) was identified as a risk factor. CONCLUSION: Delayed ischemic stroke after stent-assisted coil placement is caused by embolism from or thrombotic occlusion of stent-containing vessels after switching from dual antiplatelet therapy to monotherapy. The stent-containing vessel with incomplete aneurysm occlusion presents as a long-term thromboembolic source. Therefore, dual antiplatelet therapy for more than 9 months and late switch to monotherapy are recommended for its prevention.