Lack of aspirin effect: Aspirin resistance or resistance to taking aspirin? Gad Cotter, MD, a Eyal Shemesh, MD, d Miriam Zehavi, PhD, b Irit Dinur, RN, a Abraham Rudnick, MD, PhD, c Olga Milo, MD, a Zvi Vered, MD, a Rikardo Krakover, MD, a Edo Kaluski, MD, a and Abraham Kornberg, MD b Tel Aviv, Israel, and New York, NY Background A lack of aspirin effect on platelets after a myocardial infarction (MI) is associated with poor health outcome. This lack of effect may be due to biological resistance to aspirin or due to nonadherence (the patient is not tak- ing the aspirin, hence it has no effect). Determining which of these factors predicts poor outcome would inform potential intervention strategies. Methods Aspirin effect on platelets was assessed in a cohort of MI survivors who were divided into three groups: group A (“adherent”), patients whose platelets were affected by aspirin; group B (“nonadherent”), patients whose plate- lets showed no aspirin effect and who admitted in an interview that they were not taking their medications; and group C (potentially biologically resistant to aspirin), patients whose platelets showed no aspirin effect but maintained that they were taking their aspirin. Two health outcome measures (death, reinfarction, or rehospitalization for unstable angina; or admission for any cardiovascular causes) were assessed 12 months after enrollment. Results Seventy-three patients were enrolled and classified into groups A (“adherent,” 52 patients), B (“nonadher- ent,” 12 patients), and C (“potentially aspirin resistant,” 9 patients). Adverse events and readmission were more common in the nonadherent group (B)— 42% and 67%, respectively, when compared with the adherent group (A)— 6% and 11%, and with the potentially biologically resistant group (C)—11% and 11%. Conclusions Nonadherence is a significant mediator of poor outcome. It is important to evaluate whether or not patients are taking their medications in clinical settings and in studies that evaluate the effect of prescribed medications. (Am Heart J 2004;147:293–300.) Aspirin is prescribed as a preventative measure to survivors of a myocardial infarction (MI) 1 ; yet, the ef- fect of aspirin on platelets may not be present in all patients. 2 A recent study found that patients who have been prescribed aspirin, in whom platelet thrombox- ane (TxB2) response to aspirin is minimal or nonexist- ent, have a significantly increased risk for cardiovascu- lar morbidity. 3 One interpretation of these results is that this group of patients had a form of aspirin resis- tance, that is, their biological response to aspirin was diminished and hence their health outcome was com- promised. However, having been prescribed aspirin does not always mean that the patient is taking it. An alternative explanation is that some of these patients were nonadherent (noncompliant), that is, were not taking the aspirin as prescribed, and hence aspirin ef- fect was nonexistent. The hypothesis that the significant adverse outcome related to the lack of aspirin effect is mediated through a more generalized nonadherence pattern is supported by the fact that aspirin effect on health out- come after MI, although beneficial, is not large. 4 Hence, it is possible that a lack of aspirin effect per se will not be of much significance in a clinical setting. On the other hand, if a lack of aspirin effect is due to nonadherence, then morbidity may be determined by features that are associated with nonadherence to aspi- rin, not by the lack of effect of aspirin alone. For ex- ample, patients who are not taking their prescribed aspirin may be more likely to be nonadherent to other medications, not keep the diet recommendations, not stop smoking, and also may have psychosocial morbid- ity. All of these factors would contribute to the re- ported increased morbidity in nonadherent patients, 5–9 From the a Clinical Pharmacological Research Unit, The Cardiology Institute, and the b Hematology Institute, Assaf-Harofeh Medical Center, Zerifin, Israel, and the c Depart- ment of Behavioral Sciences, Tel Aviv University School of Medicine, Tel Aviv, Israel, and the d Departments of Psychiatry and Pediatrics, Mount Sinai Medical Center, New York, NY. Supported in part by National Institutes of Health grant MH63755 to Eyal Shemesh, MD. Submitted December 16, 2002; accepted July 24, 2003. Reprint requests: Eyal Shemesh, MD, Mount Sinai Medical Center, Box 1230, 1 Gustave L Levy Place, New York, NY 10029. E-mail: eyal.shemesh@mssm.edu 0002-8703/$ - see front matter © 2004, Elsevier Inc. All rights reserved. doi:10.1016/j.ahj.2003.07.011