Bifurcation coronary lesions and the "crush" technique.

aggregometry (LTA) is the most widely reported ex vivo technique to assess aspirin effect in platelets (1–3). With respect to our study potentially underestimating aspirin resistance in patients with unstable coronary syndromes, it should be noted that 23% (n 47) of our percutaneous coronary intervention (PCI) patients were in that category. All of these patients were sensitive to aspirin (4). To the best of our knowledge, our prospective study is the largest reported in PCI patients and is concordant with Schwartz et al (5), who reported 1 of 190 patients resistant to aspirin using 1 mol/l arachidonic acid (AA)-induced aggregation in platelet-rich plasma. The latter investigators also reported that 9% of patients exhibiting “resistance” were proven to be responders after strict adherence to aspirin treatment. These data are strikingly consistent with the results of our study (4). 2. Controversy remains regarding dose-dependent effects of aspirin on ex vivo platelet function. The latter effects may be COX-1 independent. We are currently conducting a double crossover study in outpatients that addresses these important issues. 3. With respect to the relation of ex vivo AA-induced aggregation to clinical outcomes, the single patient who was aspirinresistant in our study had suffered a stent thrombosis. We agree that large-scale studies are necessary to firmly link ex vivo platelet function measurements to the occurrence of adverse ischemic events. 4. With respect to the assertion that the thrombelastograph (TEG) assay has not undergone extensive evaluation, it should be noted that the TEG platelet mapping assay has been cleared by the Food and Drug Administration as an automated platelet aggregation system. As reported in our study, a statistically significant correlation existed between measurements by LTA and TEG (r 0.85; p 0.001). We are currently studying the relation of TEG measurements to the occurrence of recurrent ischemic events (6). The TEG has been used for many years to guide therapy in patients with postsurgical bleeding. 5. We referred to a previous study of the VerifyNow assay using propyl gallate (PG) as the agonist (7). There are no published data correlating PG as an agonist to AA in the measurement of aspirin resistance. At the time we submitted our findings to JACC, PG was the only reported agonist used in the VerifyNow assay to assess platelet responsiveness to aspirin. Moreover, no major studies describing the new AA cartridge in the VerifyNow assay had occurred prior to, and none have occurred since, our submission to JACC. 6. The relation of aspirin dose to bleeding remains controversial. We believe that this subject would be best addressed by prospective studies and not by meta-analyses. 7. We agree that there is much confusion regarding aspirin “resistance,” and this was indeed the stimulus to conduct our investigation. Stimulation by multiple pathways will affect measurements of ex vivo platelet function and the interpretation of drug “resistance.” A technique that isolates the specific pathway targeted by the drug should be used to assess drug response. Therefore, we believe that failure to inhibit the primary target of aspirin (i.e., COX-1) should be the criterion for aspirin resistance. The primary message of our study was that the prevalence of aspirin resistance using this definition is rare after treatment with a 325-mg daily dose. Finally, we emphasize that aspirin resistance may be an important phenomenon related to the occurrence of adverse clinical events. A standardized definition that will employ validated point-of-care methods to facilitate investigations in large-scale clinical trials is needed. A critical assessment of pathways affected by aspirin will also determine whether clinical events are only related to incomplete platelet COX-1 inhibition or to other anti-inflammatory or antioxidant properties of aspirin that may be dose-dependent.