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Aspirin Resistance

Cardiovascular Risk Game Changer

Yassin, Ahmed S. MD1,*; Abubakar, Hossam MD1; Mishra, Tushar MD1; Subahi, Ahmed MD1; Hartman, Melanie MD2; Ahmed, Abdelrahman MD1; Ibrahim, Walid MD1; Singh, Manmohan MD1; Pahuja, Mohit MD3

doi: 10.1097/MJT.0000000000000780
Systematic Review and Clinical Guidelines

Background: Aspirin (ASA) is the most used medication on the globe. ASA is a primary pillar of the secondary prevention of cardiovascular atherothromboembolic events. However, a fraction of the population does not respond to ASA as expected in a unique phenomenon called ASA resistance. Multiple mechanisms were described and studied in the literature to explain this phenomenon.

Area of Uncertainty: ASA resistance is an interesting phenomenon that is worth studying and reviewing. Mechanisms behind this resistance are various and although the rarity of some, it is crucial for the modern health provider to be aware of such phenomenon and its possible explanations to provide more efficient preventive cardiology practice. Our study aimed to review and conclude the evidence behind ASA resistance and its implication on the cardiovascular health.

Data Sources: We searched databases like PubMed, EMBASE, Ovid by midline, and Google Scholar for published articles and abstracts.

Results: Our systemic search revealed more than 100 articles in relation to ASA resistance. We selected 40 articles, which were relevant for this review. Various mechanisms were described in the literature, with few of them very well documented and understood. Main mechanisms include medication nonadherence, interaction with proton pump inhibitors, esterase-mediated ASA inactivation, post-coronary artery bypass grafting (CABG) MRP-4–mediated ASA consumption, cyclooxygenase-1 (COX-1) polymorphisms, high platelet turnover–associated regeneration of platelet COX-1, and the documented platelet ability of de novo COX-1 synthesis in response to thrombin and fibrinogen.

Conclusion: Multiple mechanisms of ASA resistance were described in the literature. Awareness of such interaction is important for medical practitioners. Bottom line, further studies and reviews are needed to further study this phenomenon and its implication on the cardiovascular health and hence reaching a valid evidence-based conclusion that might change the practice and improve the patient preventive health care.

1Department of Internal Medicine, Wayne State University, Detroit, MI;

2Radboud University, School of Medicine, Nijmegen, The Netherlands; and

3Department of Cardiovascular Medicine, Wayne State University, Detroit, MI.

Address for correspondence: Department of Internal Medicine, Wayne State University, 4201 St Antoine St, 2E, Detroit, MI 48201. E-mail:

The authors have no conflicts of interest to declare.

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