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

JAMA Neurol. 2015 Jul;72(7):764-72. doi: 10.1001/jamaneurol.2015.0654.


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.

Publication types

  • Comparative Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Blood Platelets / drug effects*
  • Blood Platelets / metabolism
  • Embolization, Therapeutic / methods
  • Embolization, Therapeutic / standards*
  • Female
  • Humans
  • Intracranial Aneurysm / diagnosis
  • Intracranial Aneurysm / therapy*
  • Male
  • Middle Aged
  • Platelet Activation / drug effects*
  • Platelet Activation / physiology
  • Platelet Aggregation Inhibitors / administration & dosage*
  • Prospective Studies
  • Thromboembolism / diagnosis
  • Thromboembolism / prevention & control*
  • Treatment Outcome


  • Platelet Aggregation Inhibitors

Associated data

  • CRiS/KCT0000804