Clinical Outcomes Using a Platelet Function-Guided Approach for Secondary Prevention in Patients With Ischemic Stroke or Transient Ischemic Attack

Abstract

Conclusion: Modification of antiplatelet therapy based on platelet function testing after ischemic stroke or a transient ischemic attack (TIA) results in higher rates of adverse clinical outcomes. Summary: Failure to respond to aspirin in patients with ischemic stroke is associated with an increased risk of cardiac events and death as well as decreased functional status (Ozben S et al, J Neurol 2011;258:1979-89). There are also adverse cardiac events associated with clopidogrel nonresponse. However, improvement in clinical outcomes by intensifying antiplatelet therapy has not been demonstrated in patients with ischemic stroke or TIA. The authors sought to determine clinical efficacy and safety of platelet function-guided modification of antiplatelet therapy in patients with ischemic stroke or TIA. From January 2005 to August 2007, 324 patients with ischemic stroke underwent platelet function testing using platelet aggregometry. A mean platelet aggregation >20% with 0.5 mg/mL arachidonic acid or >70% with 5 mmol/L adenosine diphosphate, or both, was defined as aspirin nonresponse. Clopidogrel nonresponse was defined as a mean platelet aggregation >40% with 5 μm/L adenosine diphosphate. Any increase in platelet therapy occurring after testing was considered a modification of antiplatelet therapy. Clinical outcomes were then compared between patients with and without platelet function-guided modification of antiplatelet therapy using univariate and propensity score-adjusted analysis. In patients with ischemic stroke or TIA, 128 (43%) and 54 (35%) were nonresponders to aspirin and clopidogrel, respectively. After platelet function testing, antiplatelet therapy was increased in 73 patients (23%). After propensity score matching, with 61 in each group, antiplatelet therapy modification was associated with significantly increased rates of death, ischemic events, or bleeding (hazard risk, 2.24; 95% confidence interval; 1.12-4.47; P = .02) compared with no modification of antiplatelet therapy. There was also a trend toward increased bleeding (hazard risk, 3.56; 95% confidence interval, 0.98-12.9; P = .05). Comment: The study found that increasing antiplatelet therapy in patients using aspirin or clopidogrel, or both, based on platelet function testing was not associated with better clinical outcomes and might be associated with higher adverse events. Why this is so is unclear. It is known that clinical factors that predict antiplatelet nonresponses are not consistent between different platelet function tests (Seok JI et al, Clin Neurol Neurosurg 2008;110:110-6). In addition, the increased risk associated with nonresponse to antiplatelet agents may reflect increased patient morbidity rather than modifiable risk factors. Current guidelines do not recommend platelet function testing for management of ischemic stroke or TIA (Furie KL, Stroke 2011;42:227-76). The data here suggest no changes are currently needed in these guidelines with respect to antiplatelet function testing.