{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T04:24:30Z","timestamp":1790051070347,"version":"4.0.1"},"reference-count":352,"publisher":"Portland Press Ltd.","issue":"8","content-domain":{"domain":["portlandpress.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2021,4,30]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Antithrombotic drugs are widely used for primary and secondary prevention, as well as treatment of many cardiovascular disorders. Over the past few decades, major advances in the pharmacology of these agents have been made with the introduction of new drug classes as novel therapeutic options. Accumulating evidence indicates that the beneficial outcomes of some of these antithrombotic agents are not solely related to their ability to reduce thrombosis. Here, we review the evidence supporting established and potential pleiotropic effects of four novel classes of antithrombotic drugs, adenosine diphosphate (ADP) P2Y12-receptor antagonists, Glycoprotein IIb\/IIIa receptor Inhibitors, and Direct Oral Anticoagulants (DOACs), which include Direct Factor Xa (FXa) and Direct Thrombin Inhibitors. Specifically, we discuss the molecular evidence supporting such pleiotropic effects in the context of cardiovascular disease (CVD) including endothelial dysfunction (ED), atherosclerosis, cardiac injury, stroke, and arrhythmia. Importantly, we highlight the role of DOACs in mitigating metabolic dysfunction-associated cardiovascular derangements. We also postulate that DOACs modulate perivascular adipose tissue inflammation and thus, may reverse cardiovascular dysfunction early in the course of the metabolic syndrome. In this regard, we argue that some antithrombotic agents can reverse the neurovascular damage in Alzheimer\u2019s and Parkinson\u2019s brain and following traumatic brain injury (TBI). Overall, we attempt to provide an up-to-date comprehensive review of the less-recognized, beneficial molecular aspects of antithrombotic therapy beyond reduced thrombus formation. We also make a solid argument for the need of further mechanistic analysis of the pleiotropic effects of antithrombotic drugs in the future.<\/jats:p>","DOI":"10.1042\/cs20201445","type":"journal-article","created":{"date-parts":[[2021,4,21]],"date-time":"2021-04-21T20:17:38Z","timestamp":1619036258000},"page":"1015-1051","update-policy":"https:\/\/doi.org\/10.1042\/crossmark_policy","source":"Crossref","is-referenced-by-count":19,"title":["The pleiotropic effects of antithrombotic drugs in the metabolic\u2013cardiovascular\u2013neurodegenerative disease continuum: impact beyond reduced clotting"],"prefix":"10.1042","volume":"135","author":[{"given":"Rana A.","family":"Alaaeddine","sequence":"first","affiliation":[{"name":"Department of Pharmacology and Toxicology, American University of Beirut, Beirut, Lebanon"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6677-4365","authenticated-orcid":false,"given":"Ibrahim","family":"AlZaim","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Toxicology, American University of Beirut, Beirut, Lebanon"},{"name":"Department of Biochemistry and Molecular Genetics, American University of Beirut, Beirut, Lebanon"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9418-4071","authenticated-orcid":false,"given":"Safaa H.","family":"Hammoud","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Therapeutics, Beirut Arab University, Beirut, Lebanon"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aya","family":"Arakji","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Toxicology, American University of Beirut, Beirut, Lebanon"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3004-5675","authenticated-orcid":false,"given":"Ali H.","family":"Eid","sequence":"additional","affiliation":[{"name":"Department of Basic Medical Sciences, College of Medicine, Qatar University, Doha, Qatar"},{"name":"Biomedical and Pharmaceutical Research Unit, QU Health, Qatar University, Doha, Qatar"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Khaled S.","family":"Abd-Elrahman","sequence":"additional","affiliation":[{"name":"University of Ottawa Brain and Mind Research Institute, Department of Cellular and Molecular Medicine University of Ottawa, Ottawa, Ontario K1H 8M5, Canada"},{"name":"Department of Pharmacology and Toxicology, Faculty of Pharmacy, Alexandria University, Alexandria 21521, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3432-3038","authenticated-orcid":false,"given":"Ahmed F.","family":"El-Yazbi","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Toxicology, American University of Beirut, Beirut, Lebanon"},{"name":"Department of Pharmacology and Toxicology, Faculty of Pharmacy, Alexandria University, Alexandria 21521, Egypt"},{"name":"Faculty of Pharmacy, Alalamein International University, Alalamein, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"288","published-online":{"date-parts":[[2021,4,21]]},"reference":[{"key":"2021113011210150900_B1","doi-asserted-by":"publisher","first-page":"281","DOI":"10.1016\/S0140-6736(15)60243-4","article-title":"Pharmacology of antithrombotic drugs: an assessment of oral antiplatelet and anticoagulant treatments","volume":"386","author":"Mega","year":"2015","journal-title":"Lancet"},{"key":"2021113011210150900_B2","doi-asserted-by":"publisher","first-page":"677","DOI":"10.1161\/CIRCRESAHA.117.308903","article-title":"Reducing the global burden of cardiovascular disease, part 1: the epidemiology and risk factors","volume":"121","author":"Joseph","year":"2017","journal-title":"Circ. 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