{"corpus_id":1480278,"paper_sha":"d79ccb4f027ff45090e64c59c4e9dfe78f22d236","doi":"10.1161/CIRCINTERVENTIONS.110.960187","arxiv_id":null,"pmid":21386092,"pmcid":null,"mag_id":2166196321,"dblp_id":null,"acl_id":null,"title":"Pharmacodynamic Effects of Different Aspirin Dosing Regimens in Type 2 Diabetes Mellitus Patients With Coronary Artery Disease","year":2011,"publication_date":"2011-04-01","venue":"Circulation. Cardiovascular Interventions","journal":{"name":"Circulation: Cardiovascular Interventions","pages":"180–187","volume":"4"},"journal_issn":null,"journal_title":null,"publication_types":["JournalArticle","ClinicalTrial"],"pubmed_pub_types":["Clinical Trial","Journal Article","Research Support, Non-U.S. Gov't"],"s2_fields_of_study":["Medicine"],"reference_count":42,"citation_count":202,"influential_citation_count":2,"is_open_access":false,"arxiv_categories":null,"arxiv_license":null,"arxiv_journal_ref":null,"mesh_headings":[{"d":"Aged","mj":false,"ui":"D000368"},{"d":"Aspirin","mj":false,"qs":[{"q":"administration & dosage","mj":true,"ui":"Q000008"},{"q":"pharmacology","mj":false,"ui":"Q000494"}],"ui":"D001241"},{"d":"Coronary Artery Disease","mj":false,"qs":[{"q":"drug therapy","mj":true,"ui":"Q000188"}],"ui":"D003324"},{"d":"Diabetes Mellitus, Type 2","mj":false,"qs":[{"q":"complications","mj":true,"ui":"Q000150"}],"ui":"D003924"},{"d":"Diabetic Angiopathies","mj":false,"qs":[{"q":"drug therapy","mj":true,"ui":"Q000188"}],"ui":"D003925"},{"d":"Dose-Response Relationship, Drug","mj":false,"ui":"D004305"},{"d":"Drug Administration Schedule","mj":false,"ui":"D004334"},{"d":"Female","mj":false,"ui":"D005260"},{"d":"Humans","mj":false,"ui":"D006801"},{"d":"Male","mj":false,"ui":"D008297"},{"d":"Middle Aged","mj":false,"ui":"D008875"},{"d":"Platelet Aggregation","mj":false,"qs":[{"q":"drug effects","mj":false,"ui":"Q000187"}],"ui":"D010974"},{"d":"Platelet Aggregation Inhibitors","mj":false,"qs":[{"q":"administration & dosage","mj":true,"ui":"Q000008"}],"ui":"D010975"},{"d":"Prospective Studies","mj":false,"ui":"D011446"},{"d":"Thromboxane B2","mj":false,"qs":[{"q":"blood","mj":false,"ui":"Q000097"}],"ui":"D013929"}],"chemicals":[{"n":"Platelet Aggregation Inhibitors","ui":"D010975","reg":"0"},{"n":"Thromboxane B2","ui":"D013929","reg":"54397-85-2"},{"n":"Aspirin","ui":"D001241","reg":"R16CO5Y76E"}],"comments_corrections":null,"source_flags":5,"s2_open_access_pdf_url":null,"s2_open_access_landing_url":null,"s2_open_access_license":null,"s2_open_access_status":null,"pmc_open_access_pdf_url":null,"pmc_open_access_landing_url":null,"pmc_open_access_license":null,"pmc_open_access_status":null,"unpaywall_open_access_pdf_url":null,"unpaywall_open_access_landing_url":null,"unpaywall_open_access_license":null,"unpaywall_open_access_status":null,"abstract":"Background— Patients with type 2 diabetes mellitus (T2DM) have reduced aspirin-induced pharmacodynamic effects. This may be attributed to increased platelet turnover rates resulting in an increased proportion of non–aspirin-inhibited platelets during the daily dosing interval. The hypothesis of this study was that an increase in the frequency of drug administration [twice daily (bid) versus once daily (od)] may provide more effective platelet inhibition in T2DM patients. Methods and Results— T2DM patients with stable coronary artery disease were prospectively recruited. Patients modified their aspirin regimen on a weekly basis according to the following scheme: 81 mg/od, 81 mg/bid, 162 mg/od, 162 mg/bid, and 325 mg/od. Pharmacodynamic assessments included light-transmittance aggregometry after arachidonic acid, collagen and adenosine diphosphate stimuli; VerifyNow-Aspirin assay; and serum thromboxane B2 (TXB2) levels. Twenty patients were analyzed. All patients were sensitive and compliant to aspirin irrespective of dose, as assessed by arachidonic acid–induced aggregation. When aspirin was administered once daily, there was no significant effect on platelet reactivity by increasing the once-daily dosing using aspirin-sensitive assays (collagen-induced aggregation and VerifyNow-Aspirin). An increase in aspirin dose by means of a second daily administration was associated with a significant reduction in platelet reactivity assessed by collagen-induced aggregation and VerifyNow-Aspirin between 81 mg/od and 81 mg/bid (P<0.05 for both assays) and between 81 mg/od and 162 mg/bid (P<0.05 for both assays). There was no impact of aspirin dosing regimens on adenosine diphosphate–induced aggregation. A dose-dependent effect of aspirin was observed on serum TXB2 levels (P=0.003). Conclusions— Aspirin dosing regimens are associated with different pharmacodynamic effects in platelets from T2DM patients and stable coronary artery disease, with a twice-daily, low-dose aspirin administration resulting in greater platelet inhibition than once-daily administration as assessed by aspirin-sensitive assays and a dose-dependent effect on serum TXB2 levels. The clinical implications of a modified aspirin regimen tailored to T2DM patients warrant further investigation. Clinical Trial Registration— URL: http://www.clinicaltrials.gov. Unique identifier: NCT01201785.","claims":[{"public_id":"cl_105f205412ac4d1bd2169822ec400462","status":"active","text":"Adding a second daily aspirin dose significantly reduced platelet reactivity between 81 mg once daily and 81 mg twice daily, and between 81 mg once daily and 162 mg twice daily, as measured by collagen-induced aggregation and the VerifyNow-Aspirin assay (P<0.05 for both comparisons and assays).","confidence":0.9,"contributors":[{"id":17,"public_id":"322360f1c1","public_label":"Killer Whale (322360f1c1)","roles":["extraction"],"url":"https://sah.borca.ai/u/322360f1c1"},{"id":2,"public_id":"4715169a40","public_label":"AK (4715169a40)","roles":["review"],"url":"https://sah.borca.ai/u/4715169a40"},{"id":1165,"public_id":"ezd9qvkvax","public_label":"The Reverser‮ 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on adenosine diphosphate–induced platelet aggregation.","confidence":0.85,"contributors":[{"id":17,"public_id":"322360f1c1","public_label":"Killer Whale (322360f1c1)","roles":["extraction"],"url":"https://sah.borca.ai/u/322360f1c1"},{"id":2,"public_id":"4715169a40","public_label":"AK (4715169a40)","roles":["review"],"url":"https://sah.borca.ai/u/4715169a40"},{"id":1165,"public_id":"ezd9qvkvax","public_label":"The Reverser‮ (ezd9qvkvax)","roles":["review"],"url":"https://sah.borca.ai/u/ezd9qvkvax"}],"url":"https://sah.borca.ai/claims/cl_2c1863db3408360b188370ce9ab75596"},{"public_id":"cl_0d6eb518e408c288a1d6b121882897a6","status":"active","text":"Increasing the once-daily aspirin dose had no significant effect on platelet reactivity as measured by collagen-induced aggregation and the VerifyNow-Aspirin assay.","confidence":0.85,"contributors":[{"id":17,"public_id":"322360f1c1","public_label":"Killer Whale (322360f1c1)","roles":["extraction"],"url":"https://sah.borca.ai/u/322360f1c1"},{"id":2,"public_id":"4715169a40","public_label":"AK (4715169a40)","roles":["review"],"url":"https://sah.borca.ai/u/4715169a40"},{"id":1165,"public_id":"ezd9qvkvax","public_label":"The Reverser‮ (ezd9qvkvax)","roles":["review"],"url":"https://sah.borca.ai/u/ezd9qvkvax"}],"url":"https://sah.borca.ai/claims/cl_0d6eb518e408c288a1d6b121882897a6"},{"public_id":"cl_802c6fd78563dbda7cf09c35ba13bb58","status":"active","text":"Serum thromboxane B2 levels showed a dose-dependent response to aspirin (P=0.003).","confidence":0.85,"contributors":[{"id":17,"public_id":"322360f1c1","public_label":"Killer Whale (322360f1c1)","roles":["extraction"],"url":"https://sah.borca.ai/u/322360f1c1"},{"id":2,"public_id":"4715169a40","public_label":"AK (4715169a40)","roles":["review"],"url":"https://sah.borca.ai/u/4715169a40"},{"id":1165,"public_id":"ezd9qvkvax","public_label":"The Reverser‮ 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