Letter by Klein Regarding Article, “Evaluation of Dose-Related Effects of Aspirin on Platelet Function: Results From the Aspirin-Induced Platelet Effect (ASPECT) Study”
To the Editor:
I read with interest the recently published report on the Aspirin-Induced Platelet Effect (ASPECT) study.1 A few issues are worth mentioning.
The overall compliance rate for daily aspirin therapy was stated to be 98%. For this 3-period/3-treatment arm crossover long-term outpatient study, the almost ideal adherence to aspirin that was achieved is different than that from many previously reported clinical studies. It is well-established that lack of compliance represents the largest practical obstacle for the success of antiplatelet therapy, particularly for aspirin. Minor bleeding events result in unreported withdrawal from antiplatelet medication. These adverse events cannot be avoided in studies designed like the ASPECT study. A recent meta-analysis of 10 antiplatelet prevention studies suggested that the range of noncompliance is 12% to 52% in all patients, with only 3% to 21% due to drug-induced adverse events.2 These data were supported by the second combined analysis of the Blockade of the Glycoprotein IIb/IIIa Receptor to Avoid Vascular Occlusion (BRAVO)3 and Sibrafiban Versus Aspirin to Yield Maximum Protection From Ischemic Heart Events Post Acute Coronary Syndromes (SYMPHONY)4 trials. Therefore, despite mandatory pill counts, these noncompliant patients do exist, must be detected among the 120 patients enrolled, and should be identified by the multiple platelet tests used in the index study.1 The data on consistent inhibition of arachidonic acid–induced aggregation exhibited in Table 5 of the article by Gurbel et al raise concerns about the diagnostic utility of the platelet tests and the “overshooting” quality of the data.
Concluding that aspirin may exert antiplatelet properties through non-cyclooxygenase-1 pathways seems to be a premature speculation, as no distinct non-cyclooxygenase–dependent mechanism has yet been identified. I very much agree with my colleagues on the importance of this specific area of research and believe that specially designed studies may be able to clarify not only this aspect but also the controversy surrounding the issue of compliance.
Gurbel PA, Bliden KP, DiChiara J, Newcomer J, Weng W, Neerchal NK, Gesheff T, Chaganti SK, Etherington A, Tantry US. Evaluation of dose-related effects of aspirin on platelet function: results from the Aspirin-Induced Platelet Effect (ASPECT) study. Circulation. 2007; 115: 3156–3164.
Topol EJ, Easton D, Harrington RA, Amarenco P, Califf RM, Graffagnino C, Davis S, Diener HC, Ferguson J, Fitzgerald D, Granett J, Shuaib A, Koudstaal PJ, Theroux P, Van de Werf F, Sigmon K, Pieper K, Vallee M, Willerson JT; Blockade of the Glycoprotein IIb/IIIa Receptor to Avoid Vascular Occlusion Trial Investigators. Randomized, double-blind, placebo-controlled, international trial of the oral IIb/IIIa antagonist lotrafiban in coronary and cerebrovascular disease. Circulation. 2003; 108: 399–406.
Newby LK Bhapkar MV, White HD, Moliterno DJ, LaPointe NM, Kandzari DE, Verheugt FW, Kramer JM, Armstrong PW, Califf RM; SYMPHONY and 2nd SYMPHONY investigators. Aspirin use post-acute coronary syndromes: intolerance, bleeding and discontinuation. J Thromb Thrombolysis. 2003; 119–128.