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Letter| Volume 119, ISSUE 3, P287, March 2006

Comments in Response to “Low-Dose Aspirin Increases Aspirin Resistance in Patients with Coronary Artery Disease”

      To the Editor:
      We read with great interest the recent article by Lee et al, “Low-Dose Aspirin Increases Aspirin Resistance in Patients with Coronary Artery Disease.”
      • Lee P.Y.
      • Chen W.H.
      • Ng W.
      • et al.
      Low-dose aspirin increases aspirin resistance in patients with coronary artery disease.
      Using a novel point-of-care device, the authors report a significant association between aspirin dose and a failure to respond according to a predetermined aspirin resistance threshold. The use of this and other means and methods have been used to determine whether an appropriate response to aspirin has been achieved. Despite the number of studies, none has prospectively correlated aspirin resistance to an increased risk for cardiovascular events.
      • Sanderson S.
      • Emery J.
      • Baglin T.
      • et al.
      Narrative review aspirin resistance and its clinical implications.
      The current study exclusively enrolled Chinese patients who averaged a particularly low body mass index (BMI). We believe this provides difficulty in extrapolating the findings to patients in the US and Europe, as well as those with higher BMIs. Recent data have suggested that increased weight is associated with a variable response to low-dose aspirin therapy.
      • Cox D.
      • Maree A.
      • Dooley M.
      • et al.
      • Tamminen M.
      • Lassial R.
      • Westerbacka J.
      • et al.
      Obesity is associated with impaired platelet-inhibitory effect of acetylsalicylic acid in nondiabetic subjects.
      Also with respect to BMI, the Women’s Health Study reported results from patients with baseline BMIs <25.0, 25.0 to 29.0, and ≥30.0. There appeared to be a trend which suggested that women with a higher BMI responded less to very low dose aspirin (100 mg every other day).
      Furthermore, the authors cite several limitations, including the failure to confirm adequate compliance to aspirin therapy. The issue of aspirin compliance and subsequent platelet response was recently investigated.
      • Schwartz K.A.
      • Schwartz D.E.
      • Ghosheh K.
      • et al.
      Compliance as a critical consideration in patients who appear to be resistant to aspirin after healing of myocardial infarction.
      Schwartz et al reported that in 129 patients with a history of myocardial infarction, 9% failed to respond to aspirin therapy, but upon observed aspirin ingestion, all but one patient responded appropriately. It also is known that concomitant use of ibuprofen and possibly other NSAIDs may attenuate the intended antiplatelet effects provided by aspirin therapy.
      • Catella-Lason F.
      • Reilly M.P.
      • Kapoor S.C.
      • et al.
      Cycloxygenase inhibitors and the antiplatelet effects of aspirin.
      • Kurth T.
      • Glynn R.J.
      • Walker A.M.
      • et al.
      Inhibition of clinical benefits of aspirin on first myocardial infarction by nonsteroidal antiinflammatory drugs.
      Finally, a previous study utilizing the same technology appears to be inconsistent with the current findings, including no relationship to aspirin dose (beta-coefficient: −0.0015, P value = not significant, 95% confidence interval: 0.997-1.000).
      • Wang J.C.
      • Aucoin-Barry D.
      • Manuelian D.
      • et al.
      Incidence of aspirin nonresponsiveness using the ultegra rapid platelet function assay-asa.
      We hope future efforts in this important area take into account compliance and drug-drug interactions, as well as emerging areas such as the impact of obesity. The focus of future work should relay clinically meaningful and practically applicable information given the broad role of aspirin in the primary and secondary prevention of cardiovascular events.

      References

        • Lee P.Y.
        • Chen W.H.
        • Ng W.
        • et al.
        Low-dose aspirin increases aspirin resistance in patients with coronary artery disease.
        Am J Med. 2005; 118: 723-727
        • Sanderson S.
        • Emery J.
        • Baglin T.
        • et al.
        Narrative review.
        Ann Intern Med. 2005; 142: 370-380
        • Cox D.
        • Maree A.
        • Dooley M.
        • et al.
        Lower bioavailability and weight dependence of enteric coated aspirin preparations (abstract).2004 (5th Annual Conference on Arteriosclerosis, Thrombosis, and Vascular Biology, San Francisco, CA, May 6-8,)
        • Tamminen M.
        • Lassial R.
        • Westerbacka J.
        • et al.
        Obesity is associated with impaired platelet-inhibitory effect of acetylsalicylic acid in nondiabetic subjects.
        Int J Obes. 2003; 27: 907-911
        • Schwartz K.A.
        • Schwartz D.E.
        • Ghosheh K.
        • et al.
        Compliance as a critical consideration in patients who appear to be resistant to aspirin after healing of myocardial infarction.
        Am J Cardiol. 2005; 95: 973-975
        • Catella-Lason F.
        • Reilly M.P.
        • Kapoor S.C.
        • et al.
        Cycloxygenase inhibitors and the antiplatelet effects of aspirin.
        N Engl J Med. 2001; 345: 1809-1817
        • Kurth T.
        • Glynn R.J.
        • Walker A.M.
        • et al.
        Inhibition of clinical benefits of aspirin on first myocardial infarction by nonsteroidal antiinflammatory drugs.
        Circulation. 2003; 108: 1191-1195
        • Wang J.C.
        • Aucoin-Barry D.
        • Manuelian D.
        • et al.
        Incidence of aspirin nonresponsiveness using the ultegra rapid platelet function assay-asa.
        Am J Cardiol. 2003; 92: 1492-1494

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