Monitoring of clopidogrel-related platelet inhibition: correlation of nonresponse with clinical outcome in supra-aortic stenting

Abstract

Background and purpose: Clopidogrel and aspirin are antiplatelet medications used in patients intended for endovascular stent placement. Although various studies have investigated individual responsiveness to clopidogrel in patients undergoing coronary interventions, there are no studies regarding patients undergoing stent placement of supra-aortic arteries supplying the brain. We analyzed platelet function in a near-patient setting to determine the effects of antiplatelet treatment in neurologic patients and correlated the results with clinical outcome after stent placement.

Materials and methods: The platelet function of 50 consecutive patients scheduled for neuro-interventional stent placement procedures was assessed by using point-of-care testing. All of the patients had symptomatic arteriosclerotic lesions. Clopidogrel effects were tested by impedance aggregometry. Fifty healthy blood donors without clopidogrel medication served as the control group.

Results: Reference values for responders and nonresponders were established from the results of the healthy control group. Fourteen (28%) of 50 neurologic patients were stratified as clopidogrel nonresponders. Adverse events were registered in 5 (10%) of 50 patients, 1 of them with a permanent neurologic deficit (1 of 50 [2%]). All 5 of the patients with adverse events were nonresponders. There was a statistically significant correlation between adverse events and clopidogrel nonresponse (Fisher exact test, P = .001).

Conclusion: A significant rate of clopidogrel nonresponders could be identified in the treated patients. Our data strongly suggest a correlation of insufficient clopidogrel-related platelet inhibition with an increased risk of thromboembolic events in supra-aortic stent placement.

Fig 1.

The fifth percentile of the results of the healthy blood donors at 52 AU is marked and used as a cutoff for nonresponsiveness in neurologic patients. Patients under clopidogrel medication show marked platelet inhibition compared with the blood donors. Neurologic patients with aggregation over 52 AU after clopidogrel medication are classified as nonresponders (also see Fig 2).

Fig 2.

Fourteen (28%) of 50 patients met the criteria of nonresponse with test results of over 52 AU. Patient 1 received a second full loading dose of 300 mg of clopidogrel before treatment after the high initial test result. Patient 7 did not receive a stent due to a free-floating thrombus. The other patients marked with numbers either suffered peri-interventional clinical events (3 of 50; patients 3, 4, and 6) or adverse events during the angiographic procedure without any clinical consequences (2 of 50; patients 2 and 5). All of the patients (5 of 50) with any type of adverse event qualified as clopidogrel nonresponders as measured by the multiplate analyzer.

Fig 3.

Patient 2 (see Fig 2) showed the second highest aggregation level of all of the patients. She developed progressive in stent clotting at the end of the procedure (A) that could be reversed by intravenous administration of tirofiban (B).