Response to the Letter Regarding Article, “Evaluation of Dose-Related Effects of Aspirin on Platelet Function: Results From the Aspirin-Induced Platelet Effect (ASPECT) Study”

Abstract

appears concerned about the uniform inhibition of arachidonic acid-induced aggregation observed in the AspirinInduced Platelet Effect (ASPECT) trial. We would like to reassure Dr Klein that the compliance of the patients in ASPECT was meticulously recorded and, as reported in the manuscript, was overall 98%. Dr Klein should also be aware of the significance of results determined by double crossover studies such as the ASPECT study and the robust statistical analyses performed. 1 Why were we not surprised by the results of the ASPECT study? In a previous study of 223 patients undergoing stenting who were treated with long-term aspirin therapy, only 1 compliant patient was resistant as determined by cyclooxygenase-1 (COX-1)-specific assays and arachidonic acid-induced aggregation in plasma and in whole blood. Interestingly, all of the noncompliant patients (3%) had high arachidonic acid-induced aggregation, suggesting the presence of "resistance," but exhibited low arachidonic acid-induced aggregation after in-hospital treatment. 2 Therefore, the message of the study Tantry et al 2 and of the ASPECT trial is that aspirin responsiveness is very high when assessed by arachidonic acidbased assays in compliant patients. Moreover, the ASPECT study demonstrates the uniformity of this property irrespective of the aspirin dose. Therefore, the our data are not "overshot." Rather, they demonstrate an important physiological effect of aspirin, that is, near uniform and potent inhibition of COX-1. A recent study by others has demonstrated concordant findings. 3 We agree that noncompliance is an important issue with any pharmacological therapy. On the basis of our data, arachidonic acid-induced platelet aggregation is a good barometer of patient compliance with aspirin and probably other drugs, as patients who are noncompliant with aspirin may also be more likely to be noncompliant with their other prescribed medications.The second important message from the ASPECT study relates to the potential antiplatelet effects of aspirin mediated by non-COX-1 pathways assessed by stimulating platelets with agonists other than arachidonic acid. We are glad that Dr Klein has also raised this issue. This is indeed a novel idea with potential clinical implications, as recent studies have demonstrated the association of adverse clinical events with "aspirin resistance" measured by a method that is not solely dependent on COX-1 activity. 4 In our article, we state that "The observation of dose-related effects despite near-complete inhibition of arachidonic acid-induced aggregation suggests that aspirin may also exert antiplatelet effects through non-COX-1 pathways" (p 3163). Clearly, we are hypothesizing a novel antiplatelet effect of aspirin that should be the focus of future research, especially in diabetic patients where the dose-dependent antiplatelet effects of aspirin may be more pronounced. 5 It took at least 70 years to determine that aspirin inhibits platelet function by acetylating COX-1 and that aspirin can be used as an effective a...

The Effect of Different Doses and Different Routes of Acetylsalicylic Acid Administration on Platelet Aggregation in Healthy Volunteers and Ischemic Stroke Patients

“…A broad range of responses from partial to complete inhibition of aggregation was observed; we can only speculate on the influence of genetics, the current status of the organism in terms of infection, organ functions and metabolism, or external circumstances. Higher thrombocytic excitability has also been repeatedly reported in acute stroke [8,9], but its role as a consequence or underlying cause of acute stroke has not been elucidated.…”

Pleiotropic effects of ezetimibe/simvastatin vs. high dose simvastatin

“…Other studies have also reported high residual platelet aggregation among patients receiving aspirin [19], particularly in patients using low doses [20]. On the other hand, lipids may increase platelet aggregation by several mechanisms [21]: (1) LDL-C, HDL-C and apolipoproteins bind specific receptors on the platelet membrane, promoting thromboxane synthesis, glycoprotein IIbIIIa expression and calcium influx [22]; (2) Modification of native LDL-C generates a platelet-activating particle [23]; and, (3) Triglycerides may also be related to platelet function.…”

Prevalence and Risk Factors for Aspirin Resistance in Elderly Patients With Type 2 Diabetes

“…In a study of 120 patients with coronary artery disease taking aspirin, 9% were aspirin-resistant by TEG 8 . In the present study, 31 patients (22.1%) were aspirin resistant according to TEG.…”