Monitoring Response to Antiplatelet Therapy: A Role in Neurointerventional Procedures?
Monitoring Response to Antiplatelet Therapy: A Role in Neurointerventional Procedures?
Abstract & Commentary
By Dana Leifer, MD, Associate Professor of Clinical Neurology, Weill Cornell Medical College. Dr. Leifer reports she is involved with grants/research support for Neurobiological Technologies and ImaRx and is on the speaker's bureau for Bristol-Myers Squibb and Sanofi Aventis.
Synopsis: Platelet function testing identifies patients who do not respond to antiplatelet therapy and are at increased risk for acute stent thrombosis after neurointerventional procedures.
Source: Lee DH, Avat A, Morsi H, et al. Dual antiplatelet therapy monitoring for neurointerventional procedures using a point-of-care platelet function test: a single-center experience. AJNR Am J Neuroradiol 2008; 29:1389-1394.
Antiplatelet therapy is the key medical therapy for prevention of ischemic stroke for most patients and is essential for preventing thrombosis after angioplasty and stenting in the cerebrovascular, coronary, and peripheral vascular circulations. Despite the use of antiplatelet therapy, many patients who are treated only medically have recurrent ischemic events, and stent thrombosis remains a significant problem after endovascular procedures. A growing body of evidence suggests that resistance to antiplatelet therapy is a significant part of the problem.
The incidence of recurrent ischemia and death appears to be between 2 and 9 times more frequent in patients who are resistant to antiplatelet therapy.1,2 The use of assays to identify resistant patients and then to guide changes in therapy has been limited, however, because traditional assays of response to antiplatelet therapy have been time-consuming and dependent on the availability of skilled laboratory technicians. Several point-of-care systems have now been developed that are easier to use and make it practical to assess response to antiplatelet agents such as aspirin and clopidogrel.
Lee et al have now examined resistance to aspirin and clopidogrel in patients undergoing neurointerventional procedures. They used one of the newer assay systems (VerifyNow; Accumetrics). Previous work with this assay demonstrated that patients with coronary artery disease and aspirin resistance were more likely to have cardiovascular death or coronary or cerebrovascular ischemic events than aspirin-responsive patients (15.6% vs. 5.3%, P<0.001).3
Lee et al studied 98 patients who underwent neurointerventional procedures during which stenting was planned. Two patients were resistant to aspirin and 42 were resistant to clopidogrel. Stents were placed in 63 patients. The main finding of the study was that acute stent thrombosis developed in 3 of the 42 clopidogrel-resistant patients, but in none of the clopidogrel responders. Stent thrombosis did not occur in aspirin-resistant patients, but, as noted above, there were only 2 aspirin-resistant patients in the study.
The investigators state that the "preferred" regimen was aspirin 325 mg/day and clopidogrel 75 mg/day after a 300 mg load for 5 to 10 days before the procedure, but it is not stated how many patients actually received this regimen. Twenty-nine of the 42 patients who were resistant to clopidogrel received an extra 300 mg dose, and assays were repeated 30 minutes later in 10 of these, 3 of whom were clopidogrel-responsive on the repeat test. Of note, 2 of the cases of stent thrombosis were among the 29 patients who received an extra dose of clopidogrel, and neither of these patients responded to clopidogrel on repeat testing. However, repeat testing may have been done too quickly for the extra dose to have its maximal effect on the assay.
The investigators also tried to identify factors that predicted a response to clopidogrel. Multivariate analysis suggested that response to clopidogrel was inversely related to patient weight and not independently related to other factors. In particular, duration of treatment prior to the procedure was not related to response.
Commentary
The results suggest that measurement of resistance to antiplatelet therapy before neurointerventional procedures may identify patients at increased risk for intraprocedural thrombosis. The paper raises the possibility that extra doses of antiplatelet therapy that convert resistant patients into responders may improve their outcome, but the paper does not answer this question. Additional studies to address this question and to investigate the potential benefits of monitoring antiplatelet medication in other cerebrovascular disorders are needed and may lead to improved outcomes.
References
1. Grotemeyer KH, Scharafinski HW, Husstedt IW. Two-year follow-up of aspirin responder and aspirin non responder. A pilot study including 180 post-stroke patients. Thromb Res 1993;71:397-403.
2. Gum PA, Kottke-Marchant K, Welsh PA, et al. A prospective, blinded determination of the natural history of aspirin resistance among stable patients with cardiovascular disease. J Am Coll Cardiol 2003;41:961-965.
3. Chen WH, Cheng X, Lee PY. Aspirin resistance and adverse clinical events in patients with coronary artery disease. Am J Med 2007;120:631-635.
Platelet function testing identifies patients who do not respond to antiplatelet therapy and are at increased risk for acute stent thrombosis after neurointerventional procedures.Subscribe Now for Access
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