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The recent United States Preventive Services Task Force guidelines on aspirin use to prevent CVD reflect this clinical tradeoff as well as the persistent struggle to define a population that would benefit from prophylactic aspirin therapy. Past clinical trials of primary CVD prevention with aspirin have not included consideration of a biomarker relevant to aspirin\u2019s mechanism of action, platelet inhibition. This approach is at odds with the paradigm used in other key areas of pharmacological CVD prevention, including antihypertensive and statin therapy, which combine cardiovascular risk assessment with the measurement of mechanistic biomarkers (eg, blood pressure and LDL [low-density lipoprotein]-cholesterol). Reliable methods for quantifying platelet activity, including light transmission aggregometry and platelet transcriptomics, exist and should be considered to identify individuals at elevated cardiovascular risk due to a hyperreactive platelet phenotype. Therefore, we propose a new, platelet-guided approach to the study of prophylactic aspirin therapy. We think that this new approach will reveal a population with hyperreactive platelets who will benefit most from primary CVD prevention with aspirin and usher in a new era of precision-guided antiplatelet therapy.<\/jats:p>","DOI":"10.1161\/atvbaha.122.318020","type":"journal-article","created":{"date-parts":[[2022,9,1]],"date-time":"2022-09-01T09:00:42Z","timestamp":1662022842000},"page":"1207-1216","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":52,"title":["Aspirin for the Primary Prevention of Cardiovascular Disease: Time for a Platelet-Guided Approach"],"prefix":"10.1161","volume":"42","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6388-2088","authenticated-orcid":true,"given":"Lucas B.","family":"Cofer","sequence":"first","affiliation":[{"name":"NYU Grossman School of Medicine."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0751-1578","authenticated-orcid":true,"given":"Tessa J.","family":"Barrett","sequence":"additional","affiliation":[{"name":"NYU Grossman School of Medicine."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8216-4647","authenticated-orcid":true,"given":"Jeffrey S.","family":"Berger","sequence":"additional","affiliation":[{"name":"NYU Grossman School of Medicine."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"e_1_3_3_2_2","volume-title":"Aspirin Use to Prevent Cardiovascular Disease: Preventive Medication","author":"U.S. Preventive Services Task Force","year":"2021","unstructured":"U.S. Preventive Services Task Force. 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