Is Aspirin Resistance a Risk Factor? - PDF Document

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  1. Clin. Cardiol. 28, 163–164 (2005) Is Aspirin Resistance a Risk Factor? Key words: aspirin resis- tance, risk factor Measured using a bedside “aggregometer,” approximately 23% of patients will fall into the category of “aspirin nonre- sponders.”2Gum et al.3show that aspirin nonresponsiveness resulted in adverse outcomes in patients at risk for stroke and cardiovascular disease. Patients who were not aspirin-resistant at 700 days had a combined outcome of death, myocardial in- farction, or stroke of 10% compared with 24% in patients who were aspirin-resistant. Recent studies have shown that patients may also be both aspirin and clopidogrel nonresponsive.4 Introduction Aspirin is the most com- monly prescribed antiplate- let drug in the world for the prevention of life-threatening vascular events. Twenty to 25 million persons in the United States take aspirin daily to What Is “Aspirin Resistance”? The term aspirin resistance may mean different things to different individuals. The TIMI risk score would seem to indi- cate that patients who had clinical endpoints despite taking as- pirin have clinical aspirin resistance. The definition is further complicated by the fact that pa- tients may not be compliant for various reasons including an “allergy” to aspirin. Often this means that they have gastroin- testinal symptoms associated with aspirin intake, although in a few instances they do have true aspirin allergy. Malabsorption due to enteric coating, drugs that would interfere with the ac- tion of aspirin, and insufficient doses of aspirin can be reasons that aspirin does not inhibit platelets adequately. Other factors such as smoking and increased catecholamine levels may stimulate platelet aggregation and overwhelm the platelet ef- fects of aspirin. Perhaps the key to the aspirin resistance story is to make sure that the patient is truly functionally aspirin resistant, that is, that none of the factors listed above is present. Second, some measurement of aspirin effect on platelet aggregability could be used to identify patients who do not respond in the usual way to aspirin therapy. prevent platelets from clotting. Aspirin acts primarily by interfering with the biosynthesis of cyclic prostanoids: thromboxane A2, prostacyclin, and other prostaglandins. It irreversibly inhibits COX-1 by acety- lation of serine-530 and induces long lasting functional de- fects of the platelets. This results in a decrease in the produc- tion of prostaglandins and thromboxane A2 and probably accounts for much of aspirin’s antithrombotic effect. It is in- teresting that the plasma half life of aspirin is only 20 minutes in circulating blood, since it is rapidly deacetylated and con- verted to salicylate in vivo. Salicylates do not affect COX-1 or COX-2 activity. Aspirin Is Cardioprotective Obviously, many take aspirin for its cardioprotective ef- fects. However, as with any drug or therapy, aspirin doesn’t al- ways work—the question is why it doesn’t. The answer may be that some patients are aspirin-resistant; if so, what is the reason for their aspirin resistance? Since platelets are the key to arterial thrombosis following atherosclerotic plaque dis- ruption, it would be helpful to know if patients are aspirin- resistant. It is now common knowledge that platelets adhere to an abnormal surface, forming an initial platelet plug, then aggregate and initiate the coagulation cascade. Vascular com- plications include ischemic stroke, peripheral arterial disease, or any of the acute coronary syndromes. A few years ago, Antman and colleagues1published the TIMI risk score in patients presenting with acute coronary syndromes. One of those risks was aspirin intake in the recent past. Though aspirin is supposed to be cardioprotective, it ob- viously wasn’t in these instances, and one can speculate as to whether or not these patients were aspirin-resistant. What Can Be Done about Aspirin Resistance? If those patients who are truly biochemically aspirin-resis- tant are identified, perhaps increasing the dose and repeating the test would be worthwhile. If the platelets still don’t re- spond adequately, it might be better to switch to another platelet-active agent such as clopidogrel, which, of course, works in a different way—namely, by blocking the adenosine diphosphate receptor. There is some evidence that acute coronary syndromes, congestive heart failure, increased body mass index, insulin re- sistance, hyperglycemia, and hypercholesterolemia may play

  2. 164 Clin. Cardiol. Vol. 28, April 2005 References a role in diminishing the response to antiplatelet therapy. Thus, these issues must be attended to very vigorously and perhaps the patient who is “aspirin-resistant” may subsequently show positive effects on platelets from aspirin. 1. Antman EM, Cohen M, Bernink PJ, McCabe CH, Horacek T, Papuchis G, Mautner B, Corbalan R, Radley D, Braunwald E: The TIMI risk score for unstable angina/non-ST elevation MI: A method for prognostication and therapeutic decision making. J Am Med Assoc2000;284(7):835–842 Wang, JC, Aucoin-Barry D, Manuelian D, Monbouquette R, Reisman M, Gray W, Block PC, Block EH, Ladenheim M, Simon DI: Incidence of as- pirin nonresponsiveness using the Ultegra Rapid Platelet Function Assay- ASA. Amer J Cardiol2003;92:1492–1494 Gum PA, Kottke-Marchant K, Welsh PA, White J, Topol JW: A prospec- tive, blinded determination of the natural history of aspirin resistance among stable patients with cardiovascular disease. J Am Coll Cardiol 2003;41 (19):961–965 Chen WH, Lee PY, Ng W, Tse HF, Lau CP: Aspirin resistance is associated with a high incidence of myonecrosis after non-urgent percutaneous coro- nary intervention despite clopidogrel pretreatment. J Am Coll Cardiol 2004; 43(6):1122–1126 2. Conclusion To answer the question posed in the title of this editorial, I do believe aspirin resistance is a risk factor if it can be demon- strated by clinical testing. 3. 4. C. Richard Conti, M.D., M.A.C.C. Editor-in-Chief