Impact of sex and gender on the efficacy of antiplatelet therapy: The female perspective

Journal of Atherosclerosis and Thrombosis

Volumn 22, Issue 2, 2015, Pages 109-125

  Basili, Stefania ^a   Raparelli, Valeria ^a   Proietti, Marco ^a   Tanzilli, Gaetano ^a   Franconi, Flavia ^b  

^a SAPIENZA UNIVERSITY OF ROME   (Italy)

^b UNIVERSITY OF SASSARI   (Italy)

Author keywords

Antiplatelet therapy; Cardiovascular disease; Gender; Sex

Indexed keywords

ABCIXIMAB; ACETYLSALICYLIC ACID; ANTITHROMBOCYTIC AGENT; CLOPIDOGREL; EPTIFIBATIDE; FIBRINOGEN RECEPTOR ANTAGONIST; METOPROLOL; PRASUGREL; TICAGRELOR; TIROFIBAN; WARFARIN;

ATHEROSCLEROSIS; BLEEDING; CARDIOVASCULAR DISEASE; CLINICAL TRIAL (TOPIC); DRUG ABSORPTION; DRUG EFFICACY; DRUG SAFETY; GENDER AND SEX; GENETIC POLYMORPHISM; HUMAN; META ANALYSIS (TOPIC); NONHUMAN; PERCUTANEOUS CORONARY INTERVENTION; PHASE 1 CLINICAL TRIAL (TOPIC); PHASE 2 CLINICAL TRIAL (TOPIC); PLATELET REACTIVITY; RANDOMIZED CONTROLLED TRIAL (TOPIC); REVIEW; THROMBOCYTE FUNCTION; AGE; CARDIOVASCULAR DISEASES; FEMALE; MALE; SEX DIFFERENCE;

AGE FACTORS; CARDIOVASCULAR DISEASES; FEMALE; HUMANS; MALE; PLATELET AGGREGATION INHIBITORS; SEX FACTORS;

EID: 84923224093     PISSN: 13403478     EISSN: 18803873     Source Type: Journal    
DOI: 10.5551/jat.24935     Document Type: Review

References (96)

1. Franconi F, Carru C, Spoletini I, Malorni W, Vella S, Mercuro G, Deidda M, Rosano G: A GENS-based approach to cardiovascular pharmacology: impact on metabolism, pharmacokinetics and pharmacodynamics. Ther Deliv, 2011; 2: 1437-1453
2. Marino M, Masella R, Bulzomi P, Campesi I: Nutrition and human health from a sex-gender perspective. Mol Aspects Med, 2011; 32: 1-70
3. WRITING GROUP MEMBERS, Lloyd-Jones D, Adams RJ, Brown TM, Carnethon M, Dai S, De Simone G, Ferguson TB, Ford E, Furie K, Gillespie C, Go A, Greenlund K, Haase N, Hailpern S, Ho PM, Howard V, Kissela B, Kittner S, Lackland D, Lisabeth L, Marelli A, McDermott MM, Meigs J, Mozaffarian D, Mussolino M, Nichol G, Roger VL, Rosamond W, Sacco R, Sorlie P, Roger VL, Thom T, Wasserthiel-Smoller S, Wong ND, Wylie-Rosett J: American Heart Association Statistics Committee and Stroke Statistics Subcommittee. Heart disease and stroke statistics--2010 update: a report from the American Heart Association. Circulation, 2010; 121: e46-e215
4. Mosca L, Benjamin EJ, Berra K, Bezanson JL, Dolor RJ, Lloyd-Jones DM, Newby LK, Piña IL, Roger VL, Shaw LJ, Zhao D, Beckie TM, Bushnell C, D'Armiento J, Kris- Etherton PM, Fang J, Ganiats TG, Gomes AS, Gracia CR, Haan CR, Jackson EA, Judelson DR, Kelepouris E, Lavie CJ, Moore A, Nussmeier NA, Ofili E, Oparil S, Ouyang P, Pinn VW, Sherif K, Smith SC, Sopko G, Chandra-Strobos N, Urbina EM, Vaccarino V, Wenger NK: Effectiveness-based guidelines for the prevention of cardiovascular disease in women-2011 Update: A Guideline From the American Heart Association. Circulation, 2011; 123: 1243-1262
5. Roger VL, Go AS, Lloyd-Jones DM, Adams RJ, Berry JD, Brown TM, Carnethon MR, Dai S, de Simone G, Ford ES, Fox CS, Fullerton HJ, Gillespie C, Greenlund KJ, Hailpern SM, Heit JA, Ho PM, Howard VJ, Kissela BM, Kittner SJ, Lackland DT, Lichtman JH, Lisabeth LD, Makuc DM, Marcus GM, Marelli A, Matchar DB, McDermott MM, Meigs JB, Moy CS, Mozaffarian D, Mussolino ME, Nichol G, Paynter NP, Rosamond WD, Sorlie PD, Stafford RS, Turan TN, Turner MB, Wong ND, Wylie-Rosett J, American Heart Association Statistics Committee and Stroke Statistics Subcommittee; Heart disease and stroke statistics--2011 update: a report from the American Heart Association. Circulation, 2011; 123: e18-e209
6. Go AS, Mozaffarian D, Roger VL, Benjamin EJ, Berry JD, Blaha MJ, Dai S, Ford ES, Fox CS, Franco S, Fullerton HJ, Gillespie C, Hailpern SM, Heit JA, Howard VJ, Huffman MD, Judd SE, Kissela BM, Kittner SJ, Lackland DT, Lichtman JH, Lisabeth LD, Mackey RH, Magid DJ, Marcus GM, Marelli A, Matchar DB, McGuire DK, Mohler ER 3rd, Moy CS, Mussolino ME, Neumar RW, Nichol G, Pandey DK, Paynter NP, Reeves MJ, Sorlie PD, Stein J, Towfighi A, Turan TN, Virani SS, Wong ND, Woo D, Turner MB; American Heart Association Statistics Committee and Stroke Statistics Subcommittee. Heart disease and stroke statistics--2014 update: a report from the American Heart Association. Circulation, 2014; 129: e28-e292
7. Mosca L, Mochari H, Christian AH, Berra K, Taubert K, Mills T, Burdick KA, Simpson SL; National study of women's awareness, preventive action, and barriers to cardiovascular health. Circulation, 2006; 113: 525-534
8. Stramba-Badiale M, Fox KM, Priori SG, Collins P, Daly C, Graham I, Jonsson B, Schenck-Gustafsson K, Tendera M; Cardiovascular diseases in women: a statement from the policy conference of the ESC. Eur Heart J, 2006; 27: 994-1005
9. Rauch U: Gender differences in anticoagulation and antithrombotic therapy. Handb Exp Pharmacol, 2012; 214: 523-542
10. Franconi F, Carru C, Malorni W, Vella S, Mercuro G: The effect of sex/gender on cardiovascular pharmacology. Curr Pharm Des, 2011; 17: 1095-1107
11. Jochmann N, Stangl K, Garbe E, Baumann G, Stangl V: Female-specific aspects in the pharmacotherapy of chronic cardiovascular diseases. Eur Heart J, 2005; 26: 1585-1595
12. Weaver WD, White HD, Wilcox RG, Aylward PE, Morris D, Guerci A, Ohman EM, Barbash GI, Betriu A, Sadowski Z, Topol EJ, Califf RM: Comparisons of characteristics and outcomes among women and men with acute myocardial infarction treated with thrombolytic therapy: GUSTO-I investigators. JAMA, 1996; 275: 777-782
13. Malacrida R, Genoni M, Maggioni AP, Spataro V, Parish S, Palmer A, Collins R, Moccetti T: A comparison of the early outcome of acute myocardial infarction in women and men. N Engl J Med, 1998; 338: 8-14
14. Vaccarino V, Berkman LF, Krumholz HM: Long-term outcome of myocardial infarction in women and men: a population perspective. Am J Epidemiol, 2000; 152: 965- 973
15. Watanabe CT, Maynard C, Ritchie JL: Comparison of short-term outcomes following coronary artery stenting in men versus women. Am J Cardiol, 2001; 88: 848-852
16. Stone GW, Grines CL, Browne KF, Marco J, Rothblaum D, O'Keefe J, Hartzler GO, Overlie P, Donohue B, Chelliah N: Comparison of in-hospital outcomes in men and women treated by either thrombolytic therapy or primary coronary angioplasty for acute myocardial infarction. Am J Cardiol, 1995; 75: 987-992
17. Lansky AJ, Pietras C, Costa RA, Tsuchiya Y, Brodie BR, Cox DA, Aymong ED, Stuckey TD, Garcia E, Tcheng JE, Mehran R, Negoita M, Fahy M, Cristea E, Turco M, Leon MB, Grines CL, Stone GW: Gender differences in outcomes after primary angioplasty versus primary stenting with and without abciximab for acute myocardial infarction: results of the Controlled Abciximab and Device Investigation to Lower Late Angioplasty Complications (CADILLAC) trial. Circulation, 2005; 111: 1611- 1618
18. Homko CJ, Santamore WP, Zamora L, Shirk G, Gaughan J, Cross R, Kashem A, Petersen S, Bove AA: Cardiovascular disease knowledge and risk perception among underserved individuals at increased risk of cardiovascular disease. J Cardiovasc Nurs, 2008; 23: 332-337
19. Blomkalns AL, Chen AY, Hochman JS, Peterson ED, Trynosky K, Diercks DB, Brogan GX Jr, Boden WE, Roe MT, Ohman EM, Gibler WB, Newby LK: CRUSADE Investigators Gender disparities in the diagnosis and treatment of non-ST-segment elevation acute coronary syndromes: large-scale observations from the CRUSADE (Can Rapid Risk Stratification of Unstable Angina Patients Suppress Adverse Outcomes With Early Implementation of the American College of Cardiology/American Heart Association Guidelines) National Quality Improvement Initiative. J Am Coll Cardiol, 2005; 45: 832-837
20. Kim ES, Menon V: Status of Women in Cardiovascular Clinical Trials. Arterioscler Thromb Vasc Biol, 2009; 29: 279-283
21. Dhruva SS, Redberg RF: Evaluating Sex Differences in Medical Device Clinical Trials Time for Action JAMA, 2012; 307: 1145-1146
22. Dhruva SS, Redberg RF: The need for sex-specific data prior to Food and Drug Administration approval. J Am Coll Cardiol, 2010; 55: 261
23. Maas AH, van der Schouw YT, Regitz-Zagrosek V, Swahn E, Appelman YE, Pasterkamp G, Ten Cate H, Nilsson PM, Huisman MV, Stam HC, Eizema K, Stramba-Badiale M: Red alert for women's heart: the urgent need for more research and knowledge on cardiovascular disease in women: proceedings of the workshop held in Brussels on gender differences in cardiovascular disease, 29 September 2010. Eur Heart J, 2011; 32: 1362-1368
24. Harris DJ, Douglas PS: Enrollment of women in cardiovascular clinical trials funded by the National Heart, Lung, and Blood Institute. N Engl J Med, 2000; 343: 475-480
25. Kim C, Fahrenbruch CE, Menon V: Enrollment of women in National Heart, Lung, and Blood Institute- Funded cardiovascular controlled trials fails to meet current federal mandates for inclusion. J Am Coll Cardiol, 2008; 52: 672-673
26. Pinnow E, Sharma P, Parekh A, Gevorkian N, Uhl K: Increasing participation of women in early phase clinical trials approved by the FDA. Womens Health Issues, 2009; 19: 89-93
27. Raz L, Miller VM: Considerations of sex and gender differences in preclinical and clinical trials. Handb Exp Pharmacol, 2012; 214: 127-147
28. Wilde O: A woman of no importance, Penguin, 2007
29. Yee DL, Sun CW, Bergeron AL, Dong JF, Bray PF: Aggregometry detects platelethyperreactivity in healthy individuals. Blood, 2005; 106: 2723-2729
30. Johnson M, Ramey E, Ramwell PW: Sex and age differences in human platelet aggregation. Nature, 1975; 253: 355-357
31. Faraday N, Goldschmidt-Clermont PJ, Bray PF: Gender differences in platelet GPIIb-IIIa activation. Thromb Haemost, 1997; 77: 748-754
32. Kurrelmeyer K, Becker L, Becker D, Yanek L, Goldschmidt- Clermont P, Bray PF: Platelet hyperreactivity in women from families with premature atherosclerosis. J Am Med Womens Assoc, 2003; 58: 272-277
33. Eidelman O, Jozwik C, Huang W, Srivastava M, Rothwell SW, Jacobowitz DM, Ji X, Zhang X, Guggino W, Wright J, Kiefer J, Olsen C, Adimi N, Mueller GP, Pollard HB: Gender dependence for a subset of the low-abundance signaling proteome in human platelets. Hum Genomics Proteomics, 2010; 2010: 164906
34. Tarantino MD, Kunicki TJ, Nugent DJ: The estrogen receptor is present in human megakaryocytes. Ann N Y Acad Sci, 1994; 714: 293-296
35. Braunstein JB, Kershner DW, Bray P, Gerstenblith G, Schulman SP, Post WS, Blumenthal RS: Interaction of hemostatic genetics with hormone therapy: new insights to explain arterial thrombosis in postmenopausal women. Chest, 2002; 121: 906-920
36. Weiss EJ, Bray PF, Tayback M, Schulman SP, Kickler TS, Becker LC, Weiss JL, Gerstenblith G, Goldschmidt-Clermont PJ: A polymorphism of a platelet glycoprotein receptor as an inherited risk factor for coronary thrombosis. N Engl J Med, 1996; 334: 1090-1094
37. Zotz RB, Klein M, Dauben HP, Moser C, Gams E, Scharf RE: Prospective analysis after coronary-artery bypass grafting: platelet GP IIIa polymorphism (HPA-1b/PIA2) is a risk factor for bypass occlusion, yocardial infarction, and death. Thromb Haemost, 2000; 83: 404-407
38. Bray PF: Platelet glycoprotein polymorphisms as risk factors for thrombosis. Curr Opin Hematol, 2000; 7: 284- 289
39. Bray PF, Howard TD, Vittinghoff E, Sane DC, Herrington DM: Effect of genetic variations in platelet glycoproteins Ibalpha and VI on the risk for coronary heart disease events in postmenopausal women taking hormone therapy. Blood, 2007; 109: 1862-1869
40. Blauwet LA, Redberg RF: The role of sex-specific results reporting in cardiovascular disease. Cardiol Rev, 2007; 15: 275-278
41. Wang TY, Angiolillo DJ, Cushman M, Sabatine MS, Bray PF, Smyth SS, Dauerman HL, French PA, Becker RC: Platelet biology and response to antiplatelet therapy in women: implications for the development and use of antiplatelet pharmacotherapies for cardiovascular disease. J Am Coll Cardiol, 2012; 59: 891-900
42. Capodanno D, Angiolillo DJ: Impact of race and gender on antithrombotic therapy. Thromb Haemost, 2010; 104: 471-484
43. Kostis WJ, Cheng JQ, Dobrzynski JM, Cabrera J, Kostis JB: Meta-Analysis of Statin Effects in Women Versus Men. J Am Coll Cardiol, 2012; 59: 572-582
44. Yerman T, Gan WQ, Sin DD: The influence of gender on the effects of aspirin in preventing myo cardial infarction. BMC Med, 2007; 5: 29
45. Hansson L, Zanchetti A, Carruthers SG, Dahlöf B, Elmfeldt D, Julius S, Ménard J, Rahn KH, Wedel H, Westerling S: Effects of intensive blood-pressure lowering and low-dose aspirin in patients with hypertension: principal results of the Hypertension Optimal Treatment (HOT) randomised trial. Lancet, 1998; 351: 1755-1762
46. Collaborative Group of the Primary Prevention Project: Low-dose aspirin and vitamin E in people at cardiovascular risk: a randomised trial in general practice. Lancet, 2001; 357: 89-95
47. Ridker PM, Cook NR, Lee IM, Gordon D, Gaziano JM, Manson JE, Hennekens CH, Buring JE: A randomized trial of low-dose aspirin in the primary prevention of cardiovascular disease in women. N Engl J Med, 2005; 352: 1293-1304
48. Belch J, MacCuish A, Campbell I, Cobbe S, Taylor R, Prescott R, Lee R, Bancroft J, MacEwan S, Shepherd J, Macfarlane P, Morris A, Jung R, Kelly C, Connacher A, Peden N, Jamieson A, Matthews D, Leese G, McKnight J, O'Brien I, Semple C, Petrie J, Gordon D, Pringle S, MacWalter R: Prevention of Progression of Arterial Disease and Diabetes Study Group; Diabetes Registry Group; Royal College of Physicians Edinburgh. The prevention of progression of arterial disease and diabetes (POPADAD) trial: factorial randomised placebo controlled trial of aspirin and antioxidants in patients with diabetes and asymptomatic peripheral arterial disease. BMJ, 2008; 337: a1840
49. Ogawa H, Nakayama M, Morimoto T, Uemura S, Kanauchi M, Doi N, Jinnouchi H, Sugiyama S, Saito Y, Japanese Primary Prevention of Atherosclerosis With Aspirin for Diabetes (JPAD) Trial Investigators: Low-dose aspirin for primary prevention of atherosclerotic events in patients with type 2 diabetes: a randomized controlled trial. JAMA, 2008; 300: 2134-2141
50. Fowkes FG, Price JF, Stewart MC, Butcher I, Leng GC, Pell AC, Sandercock PA, Fox KA, Lowe GD, Murray GD: Aspirin for Asymptomatic Atherosclerosis Trialists. Aspirin for prevention of cardiovascular events in a general population screened for a low ankle brachial index: a randomized controlled trial. JAMA, 2010; 303: 841-848
51. Zuern C.S, Lindemann S, Gawaz M: Platelet function and response to aspirin: gender-specific features and implications for female thrombotic risk and management. Semin Thromb Hemost, 2009; 35: 295-306
52. Berger JS, Roncaglioni MC, Avanzini F, Pangrazzi I, Tognoni G, Brown DL: Aspirin for the primary prevention of cardiovascular events in women and men: a sexspecific meta-analysis of randomized controlled trials. JAMA, 2006; 295: 306-313
53. Antithrombotic Trialists' (ATT) Collaboration, 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
54. Vandvik PO, Lincoff AM, Gore JM, Gutterman DD, Sonnenberg FA, Alonso-Coello P, Akl EA, Lansberg MG, Guyatt GH, Spencer FA, American College of Chest Physicians: Primary and secondary prevention of cardiovascular disease: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest, 2012; 141: e637S-68S
55. 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
56. 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
57. Anand SS, Xie CC, Mehta S, Franzosi MG, Joyner C, Chrolavicius S, Fox KA, Yusuf S, CURE Investigators: Differences in the Management and Prognosis of Women and Men Who Suffer From Acute Coronary Syndromes. J Am Coll Cardiol, 2005; 46: 1845-1851
58. Steinhubl SR, Berger PB, Mann JT 3rd, Fry ET, DeLago A, Wilmer C, Topol EJ, CREDO Investigators: Clopidogrel for the Reduction of Events During Observation. Early and sustained dual oral antiplatelet therapy following percutaneous coronary intervention: a randomized controlled trial. JAMA, 2002; 288: 2411-2420
59. Saw J, Steinhubl SR, Berger PB, Kereiakes DJ, Serebruany VL, Brennan D, Topol EJ: Clopidogrel for the Reduction of Events During Observation Investigators. Lack of adverse clopidogrel-atorvastatin clinical interaction from secondary analysis of a randomized, placebo-controlled clopidogrel trial. Circulation, 2003; 108: 921-924
60. Sabatine MS, Cannon CP, Gibson CM, López-Sendón JL, Montalescot G, Theroux P, Claeys MJ, Cools F, Hill KA, Skene AM, McCabe CH, Braunwald E, CLARITYTIMI 28 Investigators: Addition of clopidogrel to aspirin and fibrinolytic therapy for myocardial infarction with ST-segment elevation. N Engl J Med, 2005; 352: 1179- 1189
61. Chen ZM, Jiang LX, Chen YP, Xie JX, Pan HC, Peto R, Collins R, Liu LS, COMMIT (ClOpidogrel and Metoprolol in Myocardial Infarction Trial) collaborative group: Addition of clopidogrel to aspirin in 45,852 patients with acute myocardial infarction: randomised placebo-controlled trial. Lancet, 2005; 366: 1607-1621
62. Bhatt DL, Fox KA, Hacke W, Berger PB, Black HR, Boden WE, Cacoub P, Cohen EA, Creager MA, Easton JD, Flather MD, Haffner SM, Hamm CW, Hankey GJ, Johnston SC, Mak KH, Mas JL, Montalescot G, Pearson TA, Steg PG, Steinhubl SR, Weber MA, Brennan DM, Fabry-Ribaudo L, Booth J, Topol EJ, CHARISMA Investigators: Clopidogrel and aspirin versus aspirin alone for the prevention of atherothrombotic events. N Engl J Med, 2006; 354: 1706-1717
63. Berger JS, Bhatt DL, Cannon CP, Chen Z, Jiang L, Jones JB, Mehta SR, Sabatine MS, Steinhubl SR, Topol EJ, Berger PB: The relative efficacy and safety of clopidogrel in women and men a sex-specific collaborative meta-analysis. J Am Coll Cardiol, 2009; 54: 1935-1945
64. 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
65. 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, PLATO Investigators, Freij A, Thorsén M: Ticagrelor versus clopidogrel in patients with acute coronary syndromes. N Engl J Med, 2009; 361: 1045- 1057
66. Husted S, James SK, Bach RG, Becker RC, Budaj A, Heras M, Himmelmann A, Horrow J, Katus HA, Lassila R, Morais J, Nicolau JC, Steg PG, Storey RF, Wojdyla D, Wallentin L; for the PLATO study group. The efficacy of ticagrelor is maintained in women with acute coronary syndromes participating in the prospective, randomized, PLATelet inhibition and patient Outcomes (PLATO) trial. Eur Heart J, 2014 Apr 10 [Epub ahead of print]
67. Boersma E, Harrington RA, Moliterno DJ, White H, Théroux P, Van de Werf F, de Torbal A, Armstrong PW, Wallentin LC, Wilcox RG, Simes J, Califf RM, Topol EJ, Simoons ML: Platelet glycoprotein IIb/IIIa inhibitors in acute coronary syndromes: a meta-analysis of all major randomised clinical trials. Lancet, 2002; 359: 189-198
68. 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 lowdose aspirin in individuals undergoing percutaneous coronary intervention for acute coronary syndromes (CURRENT- OASIS 7): a randomised factorial trial. Lancet, 2010; 376: 1233-1243
69. Price MJ, Berger PB, Teirstein PS, Tanguay JF, Angiolillo DJ, Spriggs D, Puri S, Robbins M, Garratt KN, Bertrand OF, Stillabower ME, Aragon JR, Kandzari DE, Stinis CT, Lee MS, Manoukian SV, Cannon CP, Schork NJ, Topol EJ, GRAVITAS Investigators: Standard- vs high-dose clopidogrel based on platelet function testing after percutaneous coronary intervention: the GRAVITAS randomized trial. JAMA, 2011; 305: 1097-1105
70. Gurbel PA, Becker RC, Mann KG, Steinhubl SR, Michelson AD: Platelet function monitoring in patients with coronary artery disease. J Am Coll Cardiol, 2007; 50: 1822-1834
71. Johnson M, Ramey E, Ramwell PW: Sex and age differences in human platelet aggregation. Nature, 1975; 253: 355-357
72. Faraday N, Goldschmidt-Clermont PJ, Bray PF: Sex differences in platelet GPIIb-IIIa activation. Thromb Haemost, 1997; 77: 748-754
73. Kurrelmeyer K, Becker L, Becker D, et al: Platelet hyperreactivity in women from families with premature atherosclerosis. J Am Med Womens Assoc, 2003; 58: 272-277
74. Badimon L, Storey RF, Vilahur G: Update on lipids, inflammation and atherothrombosis. Thromb Haemost, 2011; 105 Suppl 1: S34-S42
75. Becker DM, Segal J, Vaidya D, et al: Sex differences in platelet reactivity and response to low-dose aspirin therapy. JAMA, 2006; 295: 1420-1427
76. Breet NJ, van Werkum JW, Bouman HJ, Kelder JC, Ruven HJ, Bal ET, Deneer VH, Harmsze AM, van der Heyden JA, Rensing BJ, Suttorp MJ, Hackeng CM, ten Berg JM: Comparison of platelet function tests in predicting clinical outcome in patients undergoing coronary stent implantation. JAMA, 2010; 303: 754-762
77. Parodi G, Marcucci R, Valenti R, Gori AM, Migliorini A, Giusti B, Buonamici P, Gensini GF, Abbate R, Antoniucci D: High residual platelet reactivity after clopidogrel loading and long-term cardiovascular events among patients with acute coronary syndromes undergoing PCI. JAMA, 2011; 306: 1215-1223
78. 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
79. Combescure C, Fontana P, Mallouk N, Berdague P, Labruyere C, Barazer I, Gris JC, Laporte S, Fabbro-Peray P, Reny JL: Clinical implications of clopidogrel nonresponse in cardiovascular patients: A systematic review and meta-analysis. J Thromb Haemost, 2010; 8: 923-933
80. Reny JL, Berdagué P, Poncet A, Barazer I, Nolli S, Fabbro- Peray P, Schved JF, Bounameaux H, Mach F, de Moerloose P, Fontana P, Antiplatelet Drug Resistances and Ischemic Events (ADRIE) Study Group: Antiplatelet drug response status does not predict recurrent ischemic events in stable cardiovascular patients: results of the Antiplatelet Drug Resistances and Ischemic Events study. Circulation, 2012; 125: 3201-3210
81. Moscucci M, Fox KA, Cannon CP, Klein W, López- Sendón J, Montalescot G, White K, Goldberg RJ: Predictors of major bleeding in acute coronary syndromes: the Global Registry of Acute Coronary Events (GRACE). Eur Heart J, 2003; 24: 1815-1823
82. Potpara TS1, Lip GY, Dagres N, Estner HL, Larsen TB, Blomström-Lundqvist C; Conducted by the Scientific Initiatives Committee, European Heart Rhythm Association. Management of acute coronary syndrome in patients with non-valvular atrial fibrillation: results of the European Heart Rhythm Association Survey. Europace. 2014 Feb; 16(2): 293-8. doi: 10.1093/europace/euu008
83. Lip GY, Nieuwlaat R, Pisters R, Lane DA, Crijns HJ: Refining clinical risk stratification for predicting stroke and thromboembolism in atrial fibrillation using a novel risk factor based approach: the euro heart survey on atrial fibrillation. Chest, 2010; 137: 263-272
84. Lane DA, Lip GY: Female gender is a risk factor for stroke and thromboembolism in atrial fibrillation patients. Thromb Haemost, 2009; 101: 802-805
85. Pancholy SB, Sharma PS, Pancholy DS, Patel TM, Callans DJ, Marchlinski FE: Meta-analysis of gender differences in residual stroke risk and major bleeding in patients with nonvalvular atrial fibrillation treated with oral anticoagulants. Am J Cardiol, 2014; 113: 485-490
86. Alexander KP, Chen AY, Newby LK, Schwartz JB, Redberg RF, Hochman JS, Roe MT, Gibler WB, Ohman EM, Peterson ED, CRUSADE (Can Rapid risk stratification of Unstable angina patients Suppress ADverse outcomes with Early implementation of the ACC/AHA guidelines) Investigators: Sex differences in major bleeding with glycoprotein IIb/IIIa inhibitors: results from the CRUSADE (Can Rapid risk stratification of Unstable angina patients Suppress ADverse outcomes with Early implementation of the ACC/AHA guidelines) initiative. Circulation, 2006; 114: 1380-1387
87. Cho L, Topol EJ, Balog C, Foody JM, Booth JE, Cabot C, Kleiman NS, Tcheng JE, Califf R, Lincoff AM: Clinical benefit of glycoprotein IIb/IIIa blockade with Abciximab is independent of gender: pooled analysis from EPIC, EPILOG and EPISTENT trials. Evaluation of for the Prevention of Ischemic Complications. Evaluation in Percutaneous Transluminal Coronary Angioplasty to Improve Long-Term Outcome with Abciximab GP IIb/ IIIa blockade. Evaluation of Platelet IIb/IIIa Inhibitor for Stent. J Am Coll Cardiol, 2000; 36: 381-386
88. Alexander KP, Chen AY, Roe MT, Newby LK, Gibson CM, Allen-LaPointe NM, Pollack C, Gibler WB, Ohman EM, Peterson ED; CRUSADE Investigators. Excess dosing of antiplatelet and antithrombin agents in the treatment of non-ST-segment elevation acute coronary syndromes. JAMA, 2005; 294: 3108-3116
89. Tavris DR, Gallauresi BA, Lin B, Rich SE, Shaw RE, Weintraub WS, Brindis RG, Hewitt K; Risk of local adverse events following cardiac catheterization by hemostasis device use and gender. J Invasive Cardiol, 2004; 16: 459-464
90. Ahmed B, Piper WD, Malenka D, VerLee P, Robb J, Ryan T, Herne M, Phillips W, Dauerman HL; Significantly improved vascular complications among women undergoing percutaneous coronary intervention: a report from the Northern New England Percutaneous Coronary Intervention Registry. Circ Cardiovasc Interv, 2009; 2: 423-429
91. Marso SP, Amin AP, House JA, Kennedy KF, Spertus JA, Rao SV, Cohen DJ, Messenger JC, Rumsfeld JS, National Cardiovascular Data Registry; Association between use of bleeding avoidance strategies and risk of periprocedural bleeding among patients undergoing percutaneous coronary intervention. JAMA, 2010; 303: 2156-2164
92. Lansky AJ, Mehran R, Cristea E, Parise H, Feit F, Ohman EM, White HD, Alexander KP, Bertrand ME, Desmet W, Hamon M, Stone GW; Impact of gender and antithrombin strategy on early and late clinical outcomes in patients with non-ST-elevation acute coronary syndromes (from the ACUITY trial). Am J Cardiol, 2009; 103: 1196-1203
93. Dauerman HL, Rao SV, Resnic FS, Applegate RJ; Bleeding avoidance strategies. Consensus and controversy. J Am Coll Cardiol, 2011; 58: 1-10
94. Daugherty SL, Thompson LE, Kim S, Rao SV, Subherwal S, Tsai TT, Messenger JC, Masoudi FA; Patterns of use and comparative effectiveness of bleeding avoidance strategies in men and women following percutaneous coronary interventions: an observational study from the national cardiovascular data registry. J Am Coll Cardiol, 2013; 61: 2070-2078
95. Mehilli J, Neumann FJ, Ndrepepa G, King L, Schulz S, Maimer Rodrigues da Cunha F, Jochheim D, Byrne RA, Hausleiter J, Ott I, Massberg S, Kastrati A, Pache J; Sexrelated effectiveness of bivalirudin versus abciximab and heparin in non-ST-segment elevation myocardial infarction. Am Heart J, 2013; 165: 537-543
96. Patti G, De Caterina R, Abbate R, Andreotti F, Biasucci LM, Calabrò P, Cioni G, Davì G, Di Sciascio G, Golia E, Golino P, Malatesta G, Mangiacapra F, Marcucci R, Nusca A, Parato VM, Pengo V, Prisco D, Pulcinelli F, Renda G, Ricottini E, Ruggieri B, Santilli F, Sofi F, Zimarino M; on behalf of the Working Group on Thrombosis of the Italian Society of Cardiology. Platelet function and long-term antiplatelet therapy in women: is there a gender- specificity? A 'state-of-the-art' paper. Eur Heart J, 2014; 35: 2213-23b