A Critical Appraisal of Aspirin in Secondary Prevention

Circulation

Volumn 134, Issue 23, 2016, Pages 1881-1906

  Gargiulo, Giuseppe ^a,b   Windecker, Stephan ^a   Vranckx, Pascal ^c   Gibson, Charles Michael ^d   Mehran, Roxana ^e   Valgimigli, Marco ^a,f  

^a UNIVERSITY OF BERN   (Switzerland)

^b UNIVERSITY OF NAPLES FEDERICO II   (Italy)

^c Hartcentrum Hasselt ^*  (Belgium)

^d BETH ISRAEL DEACONESS MEDICAL CENTER   (United States)

^e MOUNT SINAI SCHOOL OF MEDICINE   (United States)

^f ERASMUS MEDICAL CENTER   (Netherlands)

Author keywords

aspirin; percutaneous coronary intervention; platelet aggregation inhibitors; purinergic P2Y receptor antagonists; secondary prevention

Indexed keywords

ACETYLSALICYLIC ACID; ANTITHROMBOCYTIC AGENT; PURINERGIC P2Y RECEPTOR ANTAGONIST;

ACUTE CORONARY SYNDROME; ANTICOAGULANT THERAPY; ARTICLE; CLINICAL OUTCOME; CORONARY STENT; DRUG HYPERSENSITIVITY; DRUG MECHANISM; DRUG RESISTANCE; DUAL ANTIPLATELET THERAPY; HUMAN; MONOTHERAPY; PATHOPHYSIOLOGY; PERCUTANEOUS CORONARY INTERVENTION; PRIORITY JOURNAL; SECONDARY PREVENTION; COMBINATION DRUG THERAPY; MYOCARDIAL INFARCTION;

ACUTE CORONARY SYNDROME; ASPIRIN; DRUG THERAPY, COMBINATION; HUMANS; MYOCARDIAL INFARCTION; PLATELET AGGREGATION INHIBITORS; PURINERGIC P2Y RECEPTOR ANTAGONISTS; SECONDARY PREVENTION;

EID: 85002843615     PISSN: 00097322     EISSN: 15244539     Source Type: Journal    
DOI: 10.1161/CIRCULATIONAHA.116.023952     Document Type: Article

References (100)

1. Plato. Plato's Apology of Socrates 38a, lines 5-6.
2. Windecker S, Kolh P, Alfonso F, Collet JP, Cremer J, Falk V, Filippatos G, Hamm C, Head SJ, Juni P, Kappetein AP, Kastrati A, Knuuti J, Landmesser U, Laufer G, Neumann FJ, Richter DJ, Schauerte P, Sousa Uva M, Stefanini GG, Taggart DP, Torracca L, Valgimigli M, Wijns W, Witkowski A. 2014 ESC/EACTS guidelines on myocardial revascularization. Euro Intervention. 2015;10:1024-1094.
3. Amsterdam EA, Wenger NK, Brindis RG, Casey DE Jr, Ganiats TG, Holmes DR Jr, Jaffe AS, Jneid H, Kelly RF, Kontos MC, Levine GN, Liebson PR, Mukherjee D, Peterson ED, Sabatine MS, Smalling RW, Zieman SJ. 2014 ACC/AHA guideline for the management of patients with non-ST-elevation acute coronary syndromes: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. Circulation. 2014;130:e344-e426.
4. Fihn SD, Blankenship JC, Alexander KP, Bittl JA, Byrne JG, Fletcher BJ, Fonarow GC, Lange RA, Levine GN, Maddox TM, Naidu SS, Ohman EM, Smith PK. 2014 ACC/AHA/AATS/PCNA/SCAI/STS focused update of the guideline for the diagnosis and management of patients with stable ischemic heart disease: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines, and the American Association for Thoracic Surgery, Preventive Cardiovascular Nurses Association, Society for Cardiovascular Angiography and Interventions, and Society of Thoracic Surgeons. Circulation. 2014;130: 1749-1767.
5. O'Gara PT, Kushner FG, Ascheim DD, Casey DE, Jr., Chung MK, de Lemos JA, Ettinger SM, Fang JC, Fesmire FM, Franklin BA, Granger CB, Krumholz HM, Linderbaum JA, Morrow DA, Newby LK, Ornato JP, Ou N, Radford MJ, Tamis-Holland JE, Tommaso CL, Tracy CM, Woo YJ, Zhao DX, 2013 ACCF/AHA guideline for the management of ST-elevation myocardial infarction: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. Circulation. 2013;127:e362-e425.
6. Levine GN, Bates ER, Bittl JA, Brindis RG, Fihn SD, Fleisher LA, Granger CB, Lange RA, Mack MJ, Mauri L, Mehran R, Mukherjee D, Newby LK, O'Gara PT, Sabatine MS, Smith PK, Smith SC Jr. 2016 ACC/AHA guideline focused update on duration of dual antiplatelet therapy in patients with coronary artery disease: a report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines: an update of the 2011 ACCF/AHA/SCAI guideline for percutaneous coronary intervention, 2011 ACCF/AHA guideline for coronary artery bypass graft surgery, 2012 ACC/AHA/ACP/AATS/PCNA/SCAI/STS guideline for the diagnosis and management of patients with stable ischemic heart disease, 2013 ACCF/AHA guideline for the management of ST-elevation myocardial infarction, 2014 ACC/AHA guideline for the management of patients with non-ST-elevation acute coronary syndromes, and 2014 ACC/AHA guideline on perioperative cardiovascular evaluation and management of patients undergoing noncardiac surgery. Circulation. 2016;134:e123-e155. DOI: 10.1161/CIR.0000000000000404.
7. Davì G, Patrono C. Platelet activation and atherothrombosis. N Engl J Med. 2007;357:2482-2494. doi: 10.1056/NEJMra071014.
8. Patrono C, Andreotti F, Arnesen H, Badimon L, Baigent C, Collet JP, De Caterina R, Gulba D, Huber K, Husted S, Kristensen SD, Morais J, Neumann FJ, Rasmussen LH, Siegbahn A, Steg PG, Storey RF, Van de Werf F, Verheugt F. Antiplatelet agents for the treatment and prevention of atherothrombosis. Eur Heart J. 2011;32:2922-2932. doi: 10.1093/eurheartj/ehr373.
9. Lip GY, Windecker S, Huber K, Kirchhof P, Marin F, Ten Berg JM, Haeusler KG, Boriani G, Capodanno D, Gilard M, Zeymer U, Lane D, Storey RF, Bueno H, Collet JP, Fauchier L, Halvorsen S, Lettino M, Morais J, Mueller C, Potpara TS, Rasmussen LH, Rubboli A, Tamargo J, Valgimigli M, Zamorano JL; Document Reviewers. Management of antithrombotic therapy in atrial fibrillation patients presenting with acute coronary syndrome and/or undergoing percutaneous coronary or valve interventions: a joint consensus document of the European Society of Cardiology Working Group on Thrombosis, European Heart Rhythm Association (EHRA), European Association of Percutaneous Cardiovascular Interventions (EAPCI) and European Association of Acute Cardiac Care (ACCA) endorsed by the Heart Rhythm Society (HRS) and Asia-Pacific Heart Rhythm Society (APHRS). Eur Heart J. 2014;35:3155-3179. doi: 10.1093/eurheartj/ehu298.
10. Cattaneo M. New P2Y(12) inhibitors. Circulation. 2010;121:171-179. doi: 10.1161/CIRCULATIONAHA.109.853069.
11. Franchi F, Angiolillo DJ. Novel antiplatelet agents in acute coronary syndrome. Nat Rev Cardiol. 2015;12:30-47. doi: 10.1038/nrcardio. 2014.156.
12. Yusuf S, Zhao F, Mehta SR, Chrolavicius S, Tognoni G, Fox KK; Clopidogrel in Unstable Angina to Prevent Recurrent Events Trial Investigators. Effects of clopidogrel in addition to aspirin in patients with acute coronary syndromes without ST-segment elevation. N Engl J Med. 2001;345:494-502. doi: 10.1056/NEJMoa010746.
13. A randomised, blinded, trial of clopidogrel versus aspirin in patients at risk of ischaemic events (CAPRIE). CAPRIE Steering Committee. Lancet. 1996;348:1329-1339.
14. Wiviott SD, Braunwald E, McCabe CH, Montalescot G, Ruzyllo W, Gottlieb S, Neumann FJ, Ardissino D, De Servi S, Murphy SA, Riesmeyer J, Weerakkody G, Gibson CM, Antman EM; TRITON-TIMI 38 Investigators. Prasugrel versus clopidogrel in patients with acute coronary syndromes. N Engl J Med. 2007;357:2001-2015. doi: 10.1056/NEJMoa0706482.
15. Angiolillo DJ, Curzen N, Gurbel P, Vaitkus P, Lipkin F, Li W, Jakubowski JA, Zettler M, Effron MB, Trenk D. Pharmacodynamic evaluation of switching from ticagrelor to prasugrel in patients with stable coronary artery disease: results of the SWAP-2 Study (Switching Anti Platelet-2). J Am Coll Cardiol. 2014;63:1500-1509. doi: 10.1016/j.jacc.2013.11.032.
16. Wallentin L, Becker RC, Budaj A, Cannon CP, Emanuelsson H, Held C, Horrow J, Husted S, James S, Katus H, Mahaffey KW, Scirica BM, Skene A, Steg PG, Storey RF, Harrington RA, Freij A, Thorsén M; PLATO Investigators. Ticagrelor versus clopidogrel in patients with acute coronary syndromes. N Engl J Med. 2009;361:1045-1057. doi: 10.1056/NEJMoa0904327.
17. Bonaca MP, Bhatt DL, Cohen M, Steg PG, Storey RF, Jensen EC, Magnani G, Bansilal S, Fish MP, Im K, Bengtsson O, Oude Ophuis T, Budaj A, Theroux P, Ruda M, Hamm C, Goto S, Spinar J, Nicolau JC, Kiss RG, Murphy SA, Wiviott SD, Held P, Braunwald E, Sabatine MS; PEGASUS-TIMI 54 Steering Committee and Investigators. Long-term use of ticagrelor in patients with prior myocardial infarction. N Engl J Med. 2015;372:1791-1800. doi: 10.1056/NEJMoa1500857.
18. Mauri L, Kereiakes DJ, Yeh RW, Driscoll-Shempp P, Cutlip DE, Steg PG, Normand SL, Braunwald E, Wiviott SD, Cohen DJ, Holmes DR Jr, Krucoff MW, Hermiller J, Dauerman HL, Simon Di, Kandzari DE, Garratt KN, Lee DP, Pow TK, Ver Lee P, Rinaldi MJ, Massaro JM; DAPT Study Investigators. Twelve or 30 months of dual antiplatelet therapy after drug-eluting stents. N Engl J Med. 2014;371:2155-2166. doi: 10.1056/NEJMoa1409312.
19. Navarese EP, Andreotti F, Schulze V, Ko?odziejczak M, Buffon A, Brouwer M, Costa F, Kowalewski M, Parati G, Lip GY, Kelm M, Valgimigli M. Optimal duration of dual antiplatelet therapy after percutaneous coronary intervention with drug eluting stents: metaanalysis of randomised controlled trials. BMJ. 2015;350:h1618.
20. Mega JL, Braunwald E, Wiviott SD, Bassand JP, Bhatt DL, Bode C, Burton P, Cohen M, Cook-Bruns N, Fox KA, Goto S, Murphy SA, Plotnikov AN, Schneider D, Sun X, Verheugt FW, Gibson CM; ATLAS ACS 2-TIMI 51 Investigators. Rivaroxaban in patients with a recent acute coronary syndrome. N Engl J Med. 2012;366:9-19. doi: 10.1056/NEJMoa1112277.
21. Scirica BM, Bonaca MP, Braunwald E, De Ferrari GM, Isaza D, Lewis BS, Mehrhof F, Merlini PA, Murphy SA, Sabatine MS, Tendera M, Van de Werf F, Wilcox R, Morrow DA; TRA 2P-TIMI 50 Steering Committee Investigators. Vorapaxar for secondary prevention of thrombotic events for patients with previous myocardial infarction: a prespecified subgroup analysis of the TRA 2P-TIMI 50 trial. Lancet. 2012;380:1317-1324. doi: 10.1016/S0140-6736(12)61269-0.
22. Tricoci P, Huang Z, Held C, Moliterno DJ, Armstrong PW, Van de Werf F, White HD, Aylward PE, Wallentin L, Chen E, Lokhnygina Y, Pei J, Leonardi S, Rorick TL, Kilian AM, Jennings LH, Ambrosio G, Bode C, Cequier A, Cornel JH, Diaz R, Erkan A, Huber K, Hudson MP, Jiang L, Jukema JW, Lewis BS, Lincoff AM, Montalescot G, Nicolau JC, Ogawa H, Pfisterer M, Prieto JC, Ruzyllo W, Sinnaeve PR, Storey RF, Valgimigli M, Whellan DJ, Widimsky P, Strony J, Harrington RA, Mahaffey KW; TRACER Investigators. Thrombinreceptor antagonist vorapaxar in acute coronary syndromes. N Engl J Med. 2012;366:20-33. doi: 10.1056/NEJMoa1109719.
23. Oldgren J, Budaj A, Granger CB, Khder Y, Roberts J, Siegbahn A, Tijssen JG, Van de Werf F, Wallentin L; RE-DEEM Investigators. Dabigatran vs. placebo in patients with acute coronary syndromes on dual antiplatelet therapy: a randomized, double-blind, phase II trial. Eur Heart J. 2011;32:2781-2789. doi: 10.1093/eurheartj/ehr113.
24. Alexander JH, Lopes RD, James S, Kilaru R, He Y, Mohan P, Bhatt DL, Goodman S, Verheugt FW, Flather M, Huber K, Liaw D, Husted SE, Lopez-Sendon J, De Caterina R, Jansky P, Darius H, Vinereanu D, Cornel JH, Cools F, Atar D, Leiva-Pons JL, Keltai M, Ogawa H, Pais P, Parkhomenko A, Ruzyllo W, Diaz R, White H, Ruda M, Geraldes M, Lawrence J, Harrington RA, Wallentin L; APPRAISE-2 Investigators. Apixaban with antiplatelet therapy after acute coronary syndrome. N Engl J Med. 2011;365:699-708. doi: 10.1056/NEJMoa1105819.
25. Steg PG, Mehta SR, Jukema JW, Lip GY, Gibson CM, Kovar F, Kala P, Garcia-Hernandez A, Renfurm RW, Granger CB; RUBY-1 Investigators. RUBY-1: a randomized, double-blind, placebocontrolled trial of the safety and tolerability of the novel oral factor Xa inhibitor darexaban (YM150) following acute coronary syndrome. Eur Heart J. 2011;32:2541-2554. doi: 10.1093/eurheartj/ehr334.
26. Patrono C, García Rodríguez LA, Landolfi R, Baigent C. Low-dose aspirin for the prevention of atherothrombosis. N Engl J Med. 2005;353:2373-2383. doi: 10.1056/NEJMra052717.
27. Roth GJ, Majerus PW. The mechanism of the effect of aspirin on human platelets. I. Acetylation of a particulate fraction protein. J Clin Invest. 1975;56:624-632. doi: 10.1172/JCI108132.
28. Roth GJ, Stanford N, Majerus PW. Acetylation of prostaglandin synthase by aspirin. Proc Natl Acad Sci U S A. 1975;72:3073-3076.
29. Gargiulo G, Capodanno D, Longo G, Capranzano P, Tamburino C. Updates on NSAIDs in patients with and without coronary artery disease: pitfalls, interactions and cardiovascular outcomes. Expert Rev Cardiovasc Ther. 2014;12:1185-1203. doi: 10.1586/14779072.2014.964687.
30. Baigent C, Blackwell L, Collins R, Emberson J, Godwin J, Peto R, Buring J, Hennekens C, Kearney P, Meade T, Patrono C, Roncaglioni MC, Zanchetti A. Aspirin in the primary and secondary prevention of vascular disease: collaborative meta-analysis of individual participant data from randomised trials. Lancet. 2009;373:1849-1860.
31. Antithrombotic Trialists' Collaboration. Collaborative meta-analysis of randomised trials of antiplatelet therapy for prevention of death, myocardial infarction, and stroke in high risk patients. BMJ. 2002;324:71-86.
32. Biondi-Zoccai GG, Lotrionte M, Agostoni P, Abbate A, Fusaro M, Burzotta F, Testa L, Sheiban I, Sangiorgi G. A systematic review and meta-analysis on the hazards of discontinuing or not adhering to aspirin among 50,279 patients at risk for coronary artery disease. Eur Heart J. 2006;27:2667-2674. doi: 10.1093/eurheartj/ehl334.
33. Cattaneo M. High on-treatment platelet reactivity-definition and measurement. Thromb Haemost. 2013;109:792-798. doi: 10.1160/TH12-10-0758.
34. Kidson-Gerber G, Weaver J, Gemmell R, Prasan AM, Chong BH. Serum thromboxane B2 compared to five other platelet function tests for the evaluation of aspirin effect in stable cardiovascular disease. Heart Lung Circ. 2010;19:234-242. doi: 10.1016/j. hlc.2009.11.002.
35. Patrono C. Aspirin continues to attract research and debate, 115 years after its synthesis. Rev Esp Cardiol (Engl Ed). 2013;66:251-254.
36. Armstrong PC, Truss NJ, Ali FY, Dhanji AA, Vojnovic I, Zain ZN, Bishop-Bailey D, Paul-Clark MJ, Tucker AT, Mitchell JA, Warner TD. Aspirin and the in vitro linear relationship between thromboxane A2-mediated platelet aggregation and platelet production of thromboxane A2. J Thromb Haemost. 2008;6:1933-1943. doi: 10.1111/j.1538-7836.2008.03133.x.
37. Patrono C, Baigent C, Hirsh J, Roth G. Antiplatelet drugs: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th Edition). Chest. 2008;133:199S-233S.
38. Krasopoulos G, Brister SJ, Beattie WS, Buchanan MR. Aspirin resistance and risk of cardiovascular morbidity: systematic review and meta-analysis. BMJ. 2008;336:195-198. doi: 10.1136/bmj.39430.529549.B.E.
39. Snoep JD, Hovens MM, Eikenboom JC, van der Bom JG, Huisman MV. Association of laboratory-defined aspirin resistance with a higher risk of recurrent cardiovascular events: a systematic review and meta-analysis. Arch Intern Med. 2007;167:1593-1599. doi: 10.1001/archinte.167.15.1593.
40. Rocca B, Santilli F, Pitocco D, Mucci L, Petrucci G, Vitacolonna E, Lattanzio S, Mattoscio D, Zaccardi F, Liani R, Vazzana N, Del Ponte A, Ferrante E, Martini F, Cardillo C, Morosetti R, Mirabella M, Ghirlanda G, Davì G, Patrono C. The recovery of platelet cyclooxygenase activity explains interindividual variability in responsiveness to low-dose aspirin in patients with and without diabetes. J Thromb Haemost. 2012;10:1220-1230. doi: 10.1111/j.1538-7836.2012.04723.x.
41. Capodanno D, Patel A, Dharmashankar K, Ferreiro JL, Ueno M, Kodali M, Tomasello SD, Capranzano P, Seecheran N, Darlington A, Tello-Montoliu A, Desai B, Bass TA, Angiolillo DJ. Pharmacodynamic effects of different aspirin dosing regimens in type 2 diabetes mellitus patients with coronary artery disease. Circ Cardiovasc Interv. 2011;4:180-187. doi: 10.1161/CIRCINTERVENTIONS. 110.960187.
42. Pascale S, Petrucci G, Dragani A, Habib A, Zaccardi F, Pagliaccia F, Pocaterra D, Ragazzoni E, Rolandi G, Rocca B, Patrono C. Aspirininsensitive thromboxane biosynthesis in essential thrombocythemia is explained by accelerated renewal of the drug target. Blood. 2012;119:3595-3603. doi: 10.1182/blood-2011-06-359224.
43. Cattaneo M. Resistance to anti-platelet agents. Thromb Res. 2011;127(suppl 3):S61-S63. doi: 10.1016/S0049-3848(11) 70017-2.
44. Michelson AD, Cattaneo M, Eikelboom JW, Gurbel P, Kottke-Marchant K, Kunicki TJ, Pulcinelli FM, Cerletti C, Rao AK. Aspirin resistance: position paper of the working group on aspirin resistance. J Thromb Haemost. 2005;3:1309-1311
45. Cattaneo M. Mechanisms of variability in antiplatelet agents response. Thromb Res. 2012;130(suppl 1):S27-S28. doi: 10.1016/j.thromres.2012.08.266.
46. Agarwal SK. Single antiplatelet therapy after percutaneous coronary intervention in patients allergic to aspirin. Cardiovasc Revasc Med. 2014;15:308-310. doi: 10.1016/j.carrev.2014.04.005.
47. Lambrakis P, Rushworth GF, Adamson J, Leslie SJ. Aspirin hypersensitivity and desensitization protocols: implications for cardiac patients. Ther Adv Drug Saf. 2011;2:263-270. doi: 10.1177/2042098611422558.
48. Sánchez-Borges M. Aspirin hypersensitivity. Chem Immunol Allergy. 2014;100:132-139. doi: 10.1159/000358618.
49. Bianco M, Bernardi A, D'Ascenzo F, Cerrato E, Omedè P, Montefusco A, DiNicolantonio JJ, Zoccai GB, Varbella F, Carini G, Moretti C, Pozzi R, Gaita F. Efficacy and safety of available protocols for aspirin hypersensitivity for patients undergoing percutaneous coronary intervention: a survey and systematic review. Circ Cardiovasc Interv. 2016;9:e002896. doi: 10.1161/CIRCINTERVENTIONS. 115.002896.
50. Rossini R, Angiolillo DJ, Musumeci G, Scuri P, Invernizzi P, Bass TA, Mihalcsik L, Gavazzi A. Aspirin desensitization in patients undergoing percutaneous coronary interventions with stent implantation. Am J Cardiol. 2008;101:786-789. doi: 10.1016/j. amjcard.2007.10.045.
51. Campbell CL, Smyth S, Montalescot G, Steinhubl SR. Aspirin dose for the prevention of cardiovascular disease: a systematic review. JAMA. 2007;297:2018-2024. doi: 10.1001/jama.297.18.2018.
52. Peters RJ, Mehta SR, Fox KA, Zhao F, Lewis BS, Kopecky SL, Diaz R, Commerford PJ, Valentin V, Yusuf S; Clopidogrel in Unstable angina to prevent Recurrent Events (CURE) Trial Investigators. Effects of aspirin dose when used alone or in combination with clopidogrel in patients with acute coronary syndromes: observations from the Clopidogrel in Unstable Angina to Prevent Recurrent Events (CURE) study. Circulation. 2003;108:1682-1687. doi: 10.1161/01.CIR.0000091201.39590.C.B.
53. Mehta SR, Tanguay JF, Eikelboom JW, Jolly SS, Joyner CD, Granger CB, Faxon DP, Rupprecht HJ, Budaj A, Avezum A, Widimsky P, Steg PG, Bassand JP, Montalescot G, Macaya C, Di Pasquale G, Niemela K, Ajani AE, White HD, Chrolavicius S, Gao P, Fox KA, Yusuf S; CURRENT-OASIS 7 trial investigators. Double-dose versus standard-dose clopidogrel and high-dose versus low-dose aspirin in individuals undergoing percutaneous coronary intervention for acute coronary syndromes (CURRENT-OASIS 7): a randomised factorial trial. Lancet. 2010;376:1233-1243. doi: 10.1016/S0140-6736(10)61088-4.
54. Mahaffey KW, Wojdyla DM, Carroll K, Becker RC, Storey RF, Angiolillo DJ, Held C, Cannon CP, James S, Pieper KS, Horrow J, Harrington RA, Wallentin L; PLATO Investigators. Ticagrelor compared with clopidogrel by geographic region in the Platelet Inhibition and Patient Outcomes (PLATO) trial. Circulation. 2011;124:544-554. doi: 10.1161/CIRCULATIONAHA.111.047498.
55. Kohli P, Udell JA, Murphy SA, Cannon CP, Antman EM, Braunwald E, Wiviott SD. Discharge aspirin dose and clinical outcomes in patients with acute coronary syndromes treated with prasugrel versus clopidogrel: an analysis from the TRITON-TIMI 38 study (Trial To Assess Improvement In Therapeutic Outcomes by Optimizing Platelet Inhibition With Prasugrel-Thrombolysis in Myocardial Infarction 38). J Am Coll Cardiol. 2014;63:225-232. doi: 10.1016/j.jacc.2013.09.023.
56. Hall HM, de Lemos JA, Enriquez JR, McGuire DK, Peng SA, Alexander KP, Roe MT, Desai N, Wiviott SD, Das SR. Contemporary patterns of discharge aspirin dosing after acute myocardial infarction in the United States: results from the National Cardiovascular Data Registry (NCDR). Circ Cardiovasc Qual Outcomes. 2014;7:701-707. doi: 10.1161/CIRCOUTCOMES.113.000822.
57. Xian Y, Wang TY, McCoy LA, Effron MB, Henry TD, Bach RG, Zettler ME, Baker BA, Fonarow GC, Peterson ED. Association of discharge aspirin dose with outcomes after acute myocardial infarction: Insights from the treatment with ADP receptor inhibitors: longitudinal assessment of treatment patterns and events after acute coronary syndrome (TRANSLATE-ACS) study. Circulation. 2015;132:174-181.
58. Hernandez AF, Fleurence RL, Rothman RL. The ADAPTABLE Trial and PCORnet: shining light on a new research paradigm. Ann Intern Med. 2015;163:635-636. doi: 10.7326/M15-1460.
59. Warner TD, Nylander S, Whatling C. Anti-platelet therapy: cyclooxygenase inhibition and the use of aspirin with particular regard to dual anti-platelet therapy. Br J Clin Pharmacol. 2011;72:619-633. doi: 10.1111/j.1365-2125.2011.03943.x.
60. Schömig A, Neumann FJ, Kastrati A, Schühlen H, Blasini R, Hadamitzky M, Walter H, Zitzmann-Roth EM, Richardt G, Alt E, Schmitt C, Ulm K. A randomized comparison of antiplatelet and anticoagulant therapy after the placement of coronary-artery stents. N Engl J Med. 1996;334:1084-1089. doi: 10.1056/NEJM199604253341702.
61. Piccolo R, Windecker S. Dual antiplatelet therapy in percutaneous coronary intervention: a tale of 2 decades with new perspectives in the era of new-generation drug-eluting stents. Circ Cardiovasc Interv. 2016;9:e003587. doi: 10.1161/CIRCINTERVENTIONS. 116.003587.
62. Mehta SR, Yusuf S, Peters RJ, Bertrand ME, Lewis BS, Natarajan MK, Malmberg K, Rupprecht H, Zhao F, Chrolavicius S, Copland I, Fox KA; Clopidogrel in Unstable angina to prevent Recurrent Events trial (CURE) Investigators. Effects of pretreatment with clopidogrel and aspirin followed by long-term therapy in patients undergoing percutaneous coronary intervention: the PCI-CURE study. Lancet. 2001;358:527-533.
63. Palmerini T, Benedetto U, Bacchi-Reggiani L, Della Riva D, Biondi-Zoccai G, Feres F, Abizaid A, Hong MK, Kim BK, Jang Y, Kim HS, Park KW, Genereux P, Bhatt DL, Orlandi C, De Servi S, Petrou M, Rapezzi C, Stone GW. Mortality in patients treated with extended duration dual antiplatelet therapy after drug-eluting stent implantation: a pairwise and Bayesian network meta-analysis of randomised trials. Lancet. 2015;385:2371-2382. doi: 10.1016/S0140-6736(15)60263-X.
64. Valgimigli M, Ariotti S, Costa F. Duration of dual antiplatelet therapy after drug-eluting stent implantation: will we ever reach a consensus? Eur Heart J. 2015;36:1219-1222. doi: 10.1093/eurheartj/ehv053.
65. Valgimigli M, Borghesi M, Tebaldi M, Vranckx P, Parrinello G, Ferrari R; PROlonging Dual antiplatelet treatment after Grading stentinduced Intimal hyperplasia studY Investigators. Should duration of dual antiplatelet therapy depend on the type and/or potency of implanted stent? A pre-specified analysis from the Prolonging Dual Antiplatelet Treatment After Grading Stent-Induced Intimal Hyperplasia Study (PRODiGY). Eur Heart J. 2013;34:909-919. doi: 10.1093/eurheartj/ehs460.
66. Bonaca MP, Bhatt DL, Oude Ophuis T, Steg PG, Storey R, Cohen M, Kuder J, Im K, Magnani G, Budaj A, Theroux P, Hamm C, Ŝpinar J, Kiss RG, Dalby AJ, Medina FA, Kontny F, Aylward PE, Jensen EC, Held P, Braunwald E, Sabatine MS. Long-term tolerability of ticagrelor for the secondary prevention of major adverse cardiovascular events: a secondary analysis of the PEGASUS-TIMI 54 Trial. JAMA Cardiol. 2016;1:425-432. doi: 10.1001/jamacardio. 2016.1017.
67. Capodanno D, Gargiulo G, Buccheri S, Giacoppo D, Capranzano P, Tamburino C. Meta-analyses of dual antiplatelet therapy following drug-eluting stent implantation: do bleeding and stent thrombosis weigh similar on mortality? J Am Coll Cardiol. 2015;66:1639-1640. doi: 10.1016/j.jacc.2015.05.085.
68. Valgimigli M, Costa F, Byrne R, Haude M, Baumbach A, Windecker S. Dual antiplatelet therapy duration after coronary stenting in clinical practice: results of an EAPCI survey. EuroIntervention. 2015;11:68-74. doi: 10.4244/EIJV11I1A11.
69. Costa F, Adamo M, Ariotti S, Navarese EP, Biondi-Zoccai G, Valgimigli M. Impact of greater than 12-month dual antiplatelet therapy duration on mortality: Drug-specific or a class-effect? A meta-analysis. Int J Cardiol. 2015;201:179-181. doi: 10.1016/j. ijcard.2015.08.058.
70. Costa F, Valgimigli M. Impact of clinical presentation on dual antiplatelet therapy duration: let's re-evaluate our priorities. J Am Coll Cardiol. 2015;66:1203-1204. doi: 10.1016/j. jacc.2015.05.080.
71. Udell JA, Bonaca MP, Collet JP, Lincoff AM, Kereiakes DJ, Costa F, Lee CW, Mauri L, Valgimigli M, Park SJ, Montalescot G, Sabatine MS, Braunwald E, Bhatt DL. Long-term dual antiplatelet therapy for secondary prevention of cardiovascular events in the subgroup of patients with previous myocardial infarction: a collaborative metaanalysis of randomized trials. Eur Heart J. 2016;37:390-399. doi: 10.1093/eurheartj/ehv443.
72. Yeh RW, Kereiakes DJ, Steg PG, Windecker S, Rinaldi MJ, Gershlick AH, Cutlip DE, Cohen DJ, Tanguay JF, Jacobs A, Wiviott SD, Massaro JM, Iancu AC, Mauri L; DAPT Study Investigators. Benefits and risks of extended duration dual antiplatelet therapy after PCI in patients with and without acute myocardial infarction. J Am Coll Cardiol. 2015;65:2211-2221. doi: 10.1016/j. jacc.2015.03.003.
73. Rollini F, Franchi F, Cho JR, Degroat C, Bhatti M, Ferrante E, Patel R, Darlington A, Tello-Montoliu A, Desai B, Ferreiro J, Muniz-Lozano A, Zenni MM, Guzman LA, Bass TA, Angiolillo DJ. Cigarette smoking and antiplatelet effects of aspirin monotherapy versus clopidogrel monotherapy in patients with atherosclerotic disease: results of a prospective pharmacodynamic study. J Cardiovasc Transl Res. 2014;7:53-63. doi: 10.1007/s12265-013-9535-3.
74. Valgimigli M, Frigoli E, Leonardi S, Rothenbühler M, Gagnor A, Calabrò P, Garducci S, Rubartelli P, Briguori C, Andò G, Repetto A, Limbruno U, Garbo R, Sganzerla P, Russo F, Lupi A, Cortese B, Ausiello A, Ierna S, Esposito G, Presbitero P, Santarelli A, Sardella G, Varbella F, Tresoldi S, de Cesare N, Rigattieri S, Zingarelli A, Tosi P, van't Hof A, Boccuzzi G, Omerovic E, Sabaté M, Heg D, Jüni P, Vranckx P; MATRIX Investigators. Bivalirudin or unfractionated heparin in acute coronary syndromes. N Engl J Med. 2015;373:997-1009. doi: 10.1056/NEJMoa1507854.
75. Stone GW, Witzenbichler B, Guagliumi G, Peruga JZ, Brodie BR, Dudek D, Kornowski R, Hartmann F, Gersh BJ, Pocock SJ, Dangas G, Wong SC, Fahy M, Parise H, Mehran R; HORIZONS-AMI Trial Investigators. Heparin plus a glycoprotein IIb/IIIa inhibitor versus bivalirudin monotherapy and paclitaxel-eluting stents versus bare-metal stents in acute myocardial infarction (HORIZONS-AMI): final 3-year results from a multicentre, randomised controlled trial. Lancet. 2011;377:2193-2204. doi: 10.1016/S0140-6736(11)60764-2.
76. Mehta SR, Granger CB, Eikelboom JW, Bassand JP, Wallentin L, Faxon DP, Peters RJ, Budaj A, Afzal R, Chrolavicius S, Fox KA, Yusuf S. Efficacy and safety of fondaparinux versus enoxaparin in patients with acute coronary syndromes undergoing percutaneous coronary intervention: results from the OASIS-5 trial. J Am Coll Cardiol. 2007;50:1742-1751. doi: 10.1016/j.jacc.2007.07.042.
77. Campo G, Valgimigli M, Gemmati D, Percoco G, Catozzi L, Frangione A, Federici F, Ferrari F, Tebaldi M, Luccarelli S, Parrinello G, Ferrari R. Poor responsiveness to clopidogrel: drug-specific or class-effect mechanism? Evidence from a clopidogrel-to-ticlopidine crossover study. J Am Coll Cardiol. 2007;50:1132-1137. doi: 10.1016/j.jacc.2007.04.092.
78. Campo G, Fileti L, de Cesare N, Meliga E, Furgieri A, Russo F, Colangelo S, Brugaletta S, Ferrari R, Valgimigli M; 3T/2R Investigators. Long-term clinical outcome based on aspirin and clopidogrel responsiveness status after elective percutaneous coronary intervention: a 3T/2R (tailoring treatment with tirofiban in patients showing resistance to aspirin and/or resistance to clopidogrel) trial substudy. J Am Coll Cardiol. 2010;56:1447-1455. doi: 10.1016/j.jacc.2010.03.103.
79. Valgimigli M, Campo G, de Cesare N, Meliga E, Vranckx P, Furgieri A, Angiolillo DJ, Sabatè M, Hamon M, Repetto A, Colangelo S, Brugaletta S, Parrinello G, Percoco G, Ferrari R; Tailoring Treatment With Tirofiban in Patients Showing Resistance to Aspirin and/or Resistance to Clopidogrel (3T/2R) Investigators. Intensifying platelet inhibition with tirofiban in poor responders to aspirin, clopidogrel, or both agents undergoing elective coronary intervention: results from the double-blind, prospective, randomized Tailoring Treatment with Tirofiban in Patients Showing Resistance to Aspirin and/or Resistance to Clopidogrel study. Circulation. 2009;119:3215-3222. doi: 10.1161/CIRCULATIONAHA.108.833236.
80. Warner TD, Armstrong PC, Curzen NP, Mitchell JA. Dual antiplatelet therapy in cardiovascular disease: does aspirin increase clinical risk in the presence of potent P2Y12 receptor antagonists? Heart. 2010;96:1693-1694. doi: 10.1136/hrt.2010.205724.
81. Armstrong PC, Dhanji AR, Tucker AT, Mitchell JA, Warner TD. Reduction of platelet thromboxane A2 production ex vivo and in vivo by clopidogrel therapy. J Thromb Haemost. 2010;8:613-615. doi: 10.1111/j.1538-7836.2009.03714.x.
82. Armstrong PC, Leadbeater PD, Chan MV, Kirkby NS, Jakubowski JA, Mitchell JA, Warner TD. In the presence of strong P2Y12 receptor blockade, aspirin provides little additional inhibition of platelet aggregation. J Thromb Haemost. 2011;9:552-561. doi: 10.1111/j.1538-7836.2010.04160.x.
83. Bhavaraju K, Georgakis A, Jin J, Gartner TK, Tomiyama Y, Nurden A, Nurden P, Kunapuli SP. Antagonism of P2Y reduces physiological thromboxane levels. Platelets. 2010;21:604-609. doi: 10.3109/09537104.2010.511684.
84. Björkman JA, Zachrisson H, Forsberg GB, von Bahr H, Hansson GI, Warner TD, Nylander S. High-dose aspirin in dogs increases vascular resistance with limited additional anti-platelet effect when combined with potent P2Y12 inhibition. Thromb Res. 2013;131:313-319. doi: 10.1016/j.thromres.2013.01.029.
85. Kirkby NS, Leadbeater PD, Chan MV, Nylander S, Mitchell JA, Warner TD. Antiplatelet effects of aspirin vary with level of P2Y receptor blockade supplied by either ticagrelor or prasugrel. J Thromb Haemost. 2011;9:2103-2105. doi: 10.1111/j.1538-7836.2011.04453.x.
86. Franchi F, Rollini F, Aggarwal N, Hu J, Kureti M, Durairaj A, Duarte VE, Cho JR, Been L, Zenni MM, Bass TA, Angiolillo DJ. Pharmacodynamic comparison of prasugrel versus ticagrelor in patients with type 2 diabetes mellitus and coronary artery disease: the OPTIMUS (Optimizing Antiplatelet Therapy in Diabetes Mellitus)-4 Study. Circulation. 2016;134:780-792. doi: 10.1161/CIRCULATIONAHA. 116.023402.
87. Xian Y, Wang TY, McCoy LA, Effron MB, Henry TD, Bach RG, Zettler ME, Baker BA, Fonarow GC, Peterson ED. The association of discharge aspirin dose with outcomes after acute myocardial infarction: Insights from the translate-acs study. Circulation. 2015;132:174-81.
88. Teng R, Maya J, Butler K. Evaluation of the pharmacokinetics and pharmacodynamics of ticagrelor co-administered with aspirin in healthy volunteers. Platelets. 2013;24:615-624. doi: 10.3109/09537104.2012.748185.
89. Scavone M, Femia EA, Caroppo V, Cattaneo M. Inhibition of the platelet p2y12 receptor for adenosine diphosphate does not impair the capacity of platelet to synthesize thromboxane a2 (published online ahead of print October 29, 2015). Eur Heart J. doi: 10.1093/eurheartj/ehv551. http://eurheartj.oxfordjournals.org/content/early/2015/10/27/eurheartj.ehv551.long. Accessed October 29, 2015.
90. Rothwell PM, Price JF, Fowkes FG, Zanchetti A, Roncaglioni MC, Tognoni G, Lee R, Belch JF, Wilson M, Mehta Z, Meade TW. Shortterm effects of daily aspirin on cancer incidence, mortality, and non-vascular death: analysis of the time course of risks and benefits in 51 randomised controlled trials. Lancet. 2012;379:1602-1612. doi: 10.1016/S0140-6736(11)61720-0.
91. Thun MJ, Jacobs EJ, Patrono C. The role of aspirin in cancer prevention. Nat Rev Clin Oncol. 2012;9:259-267. doi: 10.1038/nrclinonc.2011.199.
92. Cao Y, Nishihara R, Wu K, Wang M, Ogino S, Willett WC, Spiegelman D, Fuchs CS, Giovannucci EL, Chan AT. Population-wide impact of long-term use of aspirin and the risk for cancer. JAMA Oncol. 2016;2:762-769. doi: 10.1001/jamaoncol.2015.6396.
93. Patrono C. The multifaceted clinical readouts of platelet inhibition by low-dose aspirin. J Am Coll Cardiol. 2015;66:74-85. doi: 10.1016/j.jacc.2015.05.012.
94. Hass WK, Easton JD, Adams HP Jr, Pryse-Phillips W, Molony BA, Anderson S, Kamm B. A randomized trial comparing ticlopidine hydrochloride with aspirin for the prevention of stroke in high-risk patients. Ticlopidine Aspirin Stroke Study Group. N Engl J Med. 1989;321:501-507. doi: 10.1056/NEJM198908243210804.
95. Johnston SC, Amarenco P, Albers GW, Denison H, Easton JD, Evans SR, Held P, Jonasson J, Minematsu K, Molina CA, Wang Y, Wong KS; SOCRATES Steering Committee and Investigators. Ticagrelor versus aspirin in acute stroke or transient ischemic attack. N Engl J Med. 2016;375:35-43. doi: 10.1056/NEJMoa1603060.
96. Diener HC, Bogousslavsky J, Brass LM, Cimminiello C, Csiba L, Kaste M, Leys D, Matias-Guiu J, Rupprecht HJ; MATCH investigators. Aspirin and clopidogrel compared with clopidogrel alone after recent ischaemic stroke or transient ischaemic attack in high-risk patients (MATCH): randomised, double-blind, placebo-controlled trial. Lancet. 2004;364:331-337. doi: 10.1016/S0140-6736(04)16721-4.
97. Dewilde WJ, Oirbans T, Verheugt FW, Kelder JC, De Smet BJ, Herrman JP, Adriaenssens T, Vrolix M, Heestermans AA, Vis MM, Tijsen JG, van't Hof AW, ten Berg JM; WOEST study investigators. Use of clopidogrel with or without aspirin in patients taking oral anticoagulant therapy and undergoing percutaneous coronary intervention: an open-label, randomised, controlled trial. Lancet. 2013;381:1107-1115. doi: 10.1016/S0140-6736(12)62177-1.
98. Vranckx P, Valgimigli M, Windecker S, Steg PG, Hamm C, Juni P, Garcia-Garcia HM, van Es GA, Serruys PW. Long-term ticagrelor monotherapy versus standard dual antiplatelet therapy followed by aspirin monotherapy in patients undergoing biolimus-eluting stent implantation: Rationale and design of the global leaders trial (published online ahead of print November 23, 2015). EuroIntervention. doi: 10.4244/EIJY15M11-07. http://www.pcronline.com/eurointervention/ahead-of-print/201511-07/long-term-ticagrelor-monotherapyversus-standard-dual-antiplatelet-therapy-followed-by-aspirinmonotherapy-in-patients-undergoing-biolimus-eluting-stent-implantation-rationale-and-design-of-the-global-leaders-trial. html. Accessed November 23, 2015.
99. Povsic TJ, Roe MT, Ohman EM, Steg PG, James S, Plotnikov A, Mundl H, Welsh R, Bode C, Gibson CM. A randomized trial to compare the safety of rivaroxaban vs aspirin in addition to either clopidogrel or ticagrelor in acute coronary syndrome: the design of the GEMINI-ACS-1 phase II study. Am Heart J. 2016;174:120-128. doi: 10.1016/j.ahj.2016.01.004.
100. Gargiulo G, Collet JP, Valgimigli M. Antithrombotic therapy in TAVI patients: changing concepts. EuroIntervention. 2015;11(suppl W):W92-W95. doi: 10.4244/EIJV11SWA28.