Triple versus dual antiplatelet therapy in acute coronary syndromes: Adding cilostazol to aspirin and clopidogrel

Cardiology (Switzerland)

Volumn 126, Issue 4, 2013, Pages 233-243

  Niazi, Asfandyar K ^a   Dinicolantonio, James J ^b,c   Lavie, Carl J ^d,e   O'Keefe, James H ^b   Meier, Pascal ^g   Bangalore, Sripal ^f  

^a SHIFA COLLEGE OF MEDICINE   (Pakistan)

^b UNIVERSITY OF MISSOURI KANSAS CITY   (United States)

^c Wegmans Pharmacy   (United States)

^d UNIVERSITY OF QUEENSLAND   (Australia)

^e PENNINGTON BIOMEDICAL RESEARCH CENTER   (United States)

^f NEW YORK UNIVERSITY SCHOOL OF MEDICINE   (United States)

^g UNIVERSITY COLLEGE LONDON HOSPITALS   (United Kingdom)

Author keywords

Acute coronary syndromes; Antiplatelet; Aspirin; Cilostazol; Myocardial infarction; Phosphodiesterase; Prasugrel; Secondary prevention; Thienopyridine; Ticagrelor

Indexed keywords

ACETYLSALICYLIC ACID; CILOSTAZOL; CLOPIDOGREL; DIPYRIDAMOLE; PRASUGREL; TICAGRELOR; WARFARIN;

ACUTE CORONARY SYNDROME; ANTICOAGULANT THERAPY; ANTICOAGULATION; ANTIPROLIFERATIVE ACTIVITY; BLEEDING; CEREBROVASCULAR ACCIDENT; DIABETES MELLITUS; DIARRHEA; DIZZINESS; DRUG MECHANISM; DRUG METABOLISM; DRUG SAFETY; DUAL ANTIPLATELET THERAPY; HEADACHE; HEART ATRIUM FIBRILLATION; HEART PALPITATION; HEART RATE; HUMAN; IN-STENT RESTENOSIS; INTERMETHOD COMPARISON; MEDICAL HISTORY; OUTCOME ASSESSMENT; PERCUTANEOUS CORONARY INTERVENTION; PERIPHERAL VASCULAR DISEASE; PHARYNGITIS; PRIORITY JOURNAL; RANDOMIZED CONTROLLED TRIAL (TOPIC); REVASCULARIZATION; REVIEW; RISK REDUCTION; SIDE EFFECT; SMOOTH MUSCLE RELAXATION; THROMBOCYTE ACTIVATION; TRIPLE ANTIPLATELET THERAPY; ADD ON THERAPY; CLINICAL TRIAL (TOPIC); DRUG RESISTANCE; DRUG TREATMENT FAILURE; HEREDITY; HIGH RISK PATIENT; LOADING DRUG DOSE; META ANALYSIS (TOPIC); RECURRENT DISEASE; STENT THROMBOSIS; SYSTEMATIC REVIEW (TOPIC);

ACUTE CORONARY SYNDROME; ASPIRIN; CLINICAL TRIALS AS TOPIC; DRUG THERAPY, COMBINATION; HUMANS; PHOSPHODIESTERASE 3 INHIBITORS; PLATELET AGGREGATION INHIBITORS; TETRAZOLES; TICLOPIDINE;

EID: 84885048375     PISSN: 00086312     EISSN: 14219751     Source Type: Journal    
DOI: 10.1159/000353674     Document Type: Review

References (78)

1. Wieser S, Rüthemann I, De Boni S, et al: Cost of acute coronary syndrome in Switzerland in 2008. Swiss Med Wkly 2012; 142:w13655.
2. Geeganage C, Wilcox R, Bath PM: Triple antiplatelet therapy for preventing vascular events: a systematic review and meta-analysis. BMC Med 2010; 8: 36.
3. Gurbel PA, Bliden KP, Hiatt BL, O'Connor CM: Clopidogrel for coronary stenting: response variability, drug resistance, and the effect of pretreatment platelet reactivity. Circulation 2003; 107: 2908-2913.
4. Angiolillo DJ, Fernandez-Ortiz A, Bernardo E, et al: Variability in individual responsiveness to clopidogrel: clinical implications, management, and future perspectives. J Am Coll Cardiol 2007; 49: 1505-1516.
5. Serebruany VL, Steinhubl SR, Berger PB, Malinin AI, Bhatt DL, Topol EJ: Variability in platelet responsiveness to clopidogrel among 544 individuals. J Am Coll Cardiol 2005; 45: 246-251.
6. Tousoulis D, Briasoulis A, Dhamrait SS, Antoniades C, Stefanadis C: Effective platelet inhibition by aspirin and clopidogrel: where are we now Heart 2009; 95: 850-858.
7. Aradi D, Komocsi A, Vorobcsuk A, et al: Prognostic significance of high on-clopidogrel platelet reactivity after percutaneous coronary intervention: systematic review and meta-analysis. Am Heart J 2010; 160: 543-551.
8. Becker RW, Lusis E, Sohn RL, Kline RA: Effects of cilostazol on human venous smooth muscle. Ann Vasc Surg 2005; 19: 393-397.
9. Lee JH, Park SY, Shin YW, et al: Neuroprotection by cilostazol, a phosphodiesterase type 3 inhibitor, against apoptotic white matter changes in rat after chronic cerebral hypoperfusion. Brain Res 2006; 1082: 182-191.
10. Schrör K: The pharmacology of cilostazol. Diabetes Obes Metab 2002; 4(suppl 2):S14-S19.
11. Gotoh F, Tohgi H, Hirai S, et al: Cilostazol stroke prevention study: a placebo-controlled double-blind trial for secondary prevention of cerebral infarction. J Stroke Cerebrovasc Dis 2000; 9: 147-157.
12. Min PK, Jung JH, Ko YG, Choi D, Jang Y, Shim WH: Effect of cilostazol on in-stent neointimal hyperplasia after coronary artery stenting: a quantitative coronary angiography and volumetric intravascular ultrasound study. Circ J 2007; 71: 1685-1690.
13. Han Y, Li Y, Wang S, et al: Cilostazol in addition to aspirin and clopidogrel improves long-term outcomes after percutaneous coronary intervention in patients with acute coronary syndromes: a randomized, controlled study. Am Heart J 2009; 157: 733-739.
14. Feher G, Feher A, Pusch G, Lupkovics G, Szapary L, Papp E: The genetics of antiplatelet drug resistance. Clin Genet 2009; 75: 1-18.
15. 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.
16. Matetzky S, Shenkman B, Guetta V, et al: Clopidogrel resistance is associated with increased risk of recurrent atherothrombotic events in patients with acute myocardial infarction. Circulation 2004; 109: 3171-3175.
17. Feher G, Feher A, Pusch G, et al: Clinical importance of aspirin and clopidogrel resistance. World J Cardiol 2010; 2: 171-186.
18. 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.
19. Morrow DA, Braunwald E, Bonaca MP, et al: Vorapaxar in the secondary prevention of atherothrombotic events. N Engl J Med 2012; 366: 1404-1413.
20. Geng DF, Liu M, Jin DM, Wu W, Deng J, Wang JF: Cilostazol-based triple antiplatelet therapy compared to dual antiplatelet therapy in patients with coronary stent implantation: a meta-analysis of 5,821 patients. Cardiology 2012; 122: 148-157.
21. Roth GJ, Stanford N, Majerus PW: Acetylation of prostaglandin synthase by aspirin. Proc Natl Acad Sci USA 1975; 72: 3073-3076.
22. Suh JW, Koo BK, Zhang SY, et al: Increased risk of atherothrombotic events associated with cytochrome P450 3A5 polymorphism in patients taking clopidogrel. CMAJ 2006; 174: 1715-1722.
23. Oestreich JH: Elinogrel, a reversible P2Y 12 receptor antagonist for the treatment of acute coronary syndrome and prevention of secondary thrombotic events. Curr Opin Investig Drugs 2010; 11: 340-348.
24. Hall R, Mazer CD: Antiplatelet drugs: a review of their pharmacology and management in the perioperative period. Anesth Analg 2011; 112: 292-318.
25. Gresele P, Momi S, Falcinelli E: Anti-platelet therapy: phosphodiesterase inhibitors. Br J Clin Pharmacol 2011; 72: 634-646.
26. Goto S: Cilostazol: potential mechanism of action for antithrombotic effects accompanied by a low rate of bleeding. Atheroscler Suppl 2005; 6: 3-11.
27. Shiraishi Y, Kanmura Y, Itoh T: Effect of cilostazol, a phosphodiesterase type III inhibitor, on histamine-induced increase in [Ca 2+[ i and force in middle cerebral artery of the rabbit. Br J Pharmacol 1998; 123: 869-878.
28. Hashimoto A, Miyakoda G, Hirose Y, Mori T: Activation of endothelial nitric oxide synthase by cilostazol via a cAMP/protein kinase A-and phosphatidylinositol 3-kinase/Aktdependent mechanism. Atherosclerosis 2006; 189: 350-357.
29. Takahashi S, Oida K, Fujiwara R, et al: Effect of cilostazol, a cyclic AMP phosphodiesterase inhibitor, on the proliferation of rat aortic smooth muscle cells in culture. J Cardiovasc Pharmacol 1992; 20: 900-906.
30. Hayashi S, Morishita R, Matsushita H, et al: Cyclic AMP inhibited proliferation of human aortic vascular smooth muscle cells, accompanied by induction of p53 and p21. Hypertension 2000; 35: 237-243.
31. Chuang SY, Yang SH, Chen TY, Pang JH: Cilostazol inhibits matrix invasion and modulates the gene expressions of MMP-9 and TIMP-1 in PMA-differentiated THP-1 cells. Eur J Pharmacol 2011; 670: 419-426.
32. Chuang SY, Yang SH, Pang JH: Cilostazol reduces MCP-1-induced chemotaxis and adhesion of THP-1 monocytes by inhibiting CCR2 gene expression. Biochem Biophys Res Commun 2011; 411: 402-408.
33. Aoki M, Morishita R, Hayashi S, et al: Inhibition of neointimal formation after balloon injury by cilostazol, accompanied by improvement of endothelial dysfunction and induction of hepatocyte growth factor in rat diabetes model. Diabetologia 2001; 44: 1034-1042.
34. Lee SW, Park SW, Kim YH, et al: A randomized, double-blind, multicenter comparison study of triple antiplatelet therapy with dual antiplatelet therapy to reduce restenosis after drug-eluting stent implantation in long coronary lesions: results from the DECLARE-LONG II (drug-eluting stenting followed by cilostazol treatment reduces late restenosis in patients with long coronary lesions) trial. J Am Coll Cardiol 2011; 57: 1264-1270.
35. Capranzano P, Ferreiro JL, Ueno M, et al: Pharmacodynamic effects of adjunctive cilostazol therapy in patients with coronary artery disease on dual antiplatelet therapy: impact of high on-treatment platelet reactivity and diabetes mellitus status. Catheter Cardiovasc Interv 2012; 81: 42-49.
36. Kukreja N, Onuma Y, Garcia-Garcia HM, Daemen J, van Domburg R, Serruys PW: The risk of stent thrombosis in patients with acute coronary syndromes treated with bare-metal and drug-eluting stents. JACC Cardiovasc Interv 2009; 2: 534-541.
37. Paikin JS, Wright DS, Crowther MA, Mehta SR, Eikelboom JW: Triple antithrombotic therapy in patients with atrial fibrillation and coronary artery stents. Circulation 2010; 121: 2067-2070.
38. Toyonaga S, Nakatsu T, Murakami T, et al: Effects of cilostazol on heart rate and its variation in patients with atrial fibrillation associated with bradycardia. J Cardiovasc Pharmacol Ther 2000; 5: 183-191.
39. Smith JG, Wieloch M, Koul S, et al: Triple antithrombotic therapy following an acute coronary syndrome: prevalence, outcomes and prognostic utility of the HAS-BLED score. Eurointervention 2012; 8: 672-678.
40. Jang SW, Rho TH, Kim DB, et al: Optimal antithrombotic strategy in patients with atrial fibrillation after coronary stent implantation. Korean Circ J 2011; 41: 578-582.
41. Camm AJ, Lip GY, De Caterina R, Savelieva I, Atar D, Hohnloser SH, Hindricks G, Kirchhof P; ESC Committee for Practice Guidelines (CPG), Bax JJ, Baumgartner H, Ceconi C, Dean V, Deaton C, Fagard R, Funck-Brentano C, Hasdai D, Hoes A, Kirchhof P, Knuuti J, Kolh P, McDonagh T, Moulin C, Popescu BA, Reiner Z, Sechtem U, Sirnes PA, Tendera M, Torbicki A, Vahanian A, Windecker S; Document Reviewers, Vardas P, Al-Attar N, Alfieri O, Angelini A, Blömstrom-Lundqvist C, Colonna P, De Sutter J, Ernst S, Goette A, Gorenek B, Hatala R, Heidbüchel H, Heldal M, Kristensen SD, Kolh P, Le Heuzey JY, Mavrakis H, Mont L, Filardi PP, Ponikowski P, Prendergast B, Rutten FH, Schotten U, Van Gelder IC, Verheugt FW: 2012 focused update of the ESC Guidelines for the management of atrial fibrillation: an update of the 2010 ESC Guidelines for the management of atrial fibrillation. Developed with the special contribution of the European Heart Rhythm Association. Eur Heart J 2012; 33: 2719-2747.
42. Shinohara Y, Katayama Y, Uchiyama S, et al: Cilostazol for prevention of secondary stroke (CSPS 2): an aspirin-controlled, doubleblind, randomised non-inferiority trial. Lancet Neurol 2010; 9: 959-968.
43. DiNicolantonio JJ, Lavie CJ, Fares H, et al: Meta-analysis of cilostazol versus aspirin for the secondary prevention of stroke. Am J Cardiol 2013 [Ahead of print].
44. Heo SH, Lee JS, Kim BJ, Hwang KJ, Kim JH, Chang DI: Effects of cilostazol against the progression of carotid IMT in symptomatic ischemic stroke patients. J Neurol 2013; 260: 122-130.
45. Wang TH, Bhatt DL, Topol EJ: Aspirin and clopidogrel resistance: an emerging clinical entity. Eur Heart J 2006; 27: 647-654.
46. Fernando H, Dart AM, Peter K, Shaw JA: Proton pump inhibitors, genetic polymorphisms and response to clopidogrel therapy. Thromb Haemost 2011; 105: 933-944.
47. Haraguchi K, Miyachi S, Izumi T, et al: Resistance to antiplatelet agents assessed by a point-of-care platelet function test and thromboembolic adverse events in neurointervention. No Shinkei Geka 2012; 40: 399-406.
48. Shim CY, Yoon SJ, Park S, et al: The clopidogrel resistance can be attenuated with triple antiplatelet therapy in patients undergoing drug-eluting stents implantation. Int J Cardiol 2009; 134: 351-355.
49. Angiolillo DJ, Bernardo E, Ramirez C, et al: Insulin therapy is associated with platelet dysfunction in patients with type 2 diabetes mellitus on dual oral antiplatelet treatment. J Am Coll Cardiol 2006; 48: 298-304.
50. Angiolillo DJ, Capranzano P, Goto S, et al: A randomized study assessing the impact of cilostazol on platelet function profiles in patients with diabetes mellitus and coronary artery disease on dual antiplatelet therapy: results of the OPTIMUS-2 study. Eur Heart J 2008; 29: 2202-2211.
51. Jeong YH, Tantry US, Park Y, et al: Pharmacodynamic effect of cilostazol plus standard clopidogrel versus double-dose clopidogrel in patients with type 2 diabetes undergoing percutaneous coronary intervention. Diabetes Care 2012; 35: 2194-2197.
52. Yang TH, Kim DI, Kim JY, et al: Comparison of triple anti-platelet therapy (aspirin, clopidogrel, and cilostazol) and double anti-platelet therapy (aspirin and clopidogrel) on platelet aggregation in type 2 diabetic patients undergoing drug-eluting stent implantation. Korean Circ J 2009; 39: 462-466.
53. Hu T, Ma H, Li H, Ren J: Efficacy of cilostazol in patients with acute coronary syndrome after percutaneous coronary intervention. Am J Ther 2013; 20: 151-153.
54. Rogers KC, Faircloth JM, Finks SW: Use of cilostazol in percutaneous coronary interventions. Ann Pharmacother 2012; 46: 839-850.
55. Takagi H, Umemoto T: Benefit, rather than safety, of cilostazol for long-term mortality in patients undergoing percutaneous coronary intervention: a meta-analysis of randomized trials. Int J Cardiol 2011; 153: 74-76.
56. Tamhane U, Meier P, Chetcuti S, et al: Efficacy of cilostazol in reducing restenosis in patients undergoing contemporary stent based PCI: a meta-analysis of randomised controlled trials. Eurointervention 2009; 5: 384-393.
57. Singh I, Shafiq N, Pandhi P, et al: Triple antiplatelet therapy vs dual antiplatelet therapy in patients undergoing percutaneous coronary intervention: an evidence-based approach to answering a clinical query. Br J Clin Pharmacol 2009; 68: 4-13.
58. Jang JS, Jin HY, Seo JS, et al: A meta-analysis of randomized controlled trials appraising the efficacy and safety of cilostazol after coronary artery stent implantation. Cardiology 2012; 122: 133-143.
59. Dawson DL, Cutler BS, Hiatt WR, Hobson RW, Martin JD, Bortey EB, Forbes WP, Strandness DE: A comparison of cilostazol and pentoxifylline for treating intermittent claudication. Am J Med 2000; 109: 523-530.
60. Money SR, Herd JA, Isaacsohn JL, Davidson M, Cutler B, Heckman J, Forbes WP: Effect of cilostazol on walking distances in patients with intermittent claudication caused by peripheral vascular disease. J Vasc Surg 1998; 27: 267-274, discussion 274-275.
61. Liu Y, Shakur Y, Yoshitake M, Kambayashi J: Cilostazol: a dual inhibitor of cyclic nucleotide phosphodiesterase type 3 and adenosine uptake. Cardiovasc Drug Rev 2006; 19: 369-386.
62. Woo SK, Kang WK, Kwon KI: Pharmacokinetic and pharmacodynamic modeling of the antiplatelet and cardiovascular effects of cilostazol in healthy humans. Clin Pharmacol Ther 2002; 71: 246-252.
63. Toyonaga S, Nakatsu T, Murakami T, Kusachi S, Mashima K, Tominaga Y, Yamane S, Uesugi T, Kanai H, Tsuji T: Effects of cilostazol on heart rate and its variation in patients with atrial fibrillation associated with bradycardia. J Cardiovasc Pharmacol Ther 2000; 5: 183-191.
64. Wiviott SD, Braunwald E, McCabe CH, et al: Prasugrel versus clopidogrel in patients with acute coronary syndromes. N Engl J Med 2007; 357: 2001-2015.
65. US Food and Drug Administration, Cardiovascular and Renal Drugs Advisory Committee: The FDA prasugrel secondary review. http://www.fda.gov/ohrms/dockets/ ac/09/briefing/2009-4412b1-00-FDA.htm.
66. DiNicolantonio JJ, Serebruany VL: Angiotensin receptor blockers worsen renal function and dyspnea on ticagrelor: a potential ticagrelor-angiotensin receptor blocker interaction Clin Cardiol 2012; 35: 647-648.
67. Wallentin L, Becker RC, Budaj A, et al: Ticagrelor versus clopidogrel in patients with acute coronary syndromes. N Engl J Med 2009; 361: 1045-1057.
68. DiNicolantonio JJ, Can MM, Serebruany VL: Lost in follow-up rates in TRACER, ATLAS ACS 2, TRITON and TRA 2P trials: challenging PLATO mortality rates. Int J Cardiol 2013; 164: 255-258.
69. DiNicolantonio JJ, Serebruany VL: Comparing ticagrelor versus clopidogrel in patients with a history of cerebrovascular disease: a net clinical harm Stroke 2012; 43: 3409-3410.
70. Serebruany VL, DiNicolantonio JJ, Can MM: Mortality in the TRACER and ATLAS ACS 2 trials: two more reasons to audit vital records in PLATO. Cardiology 2012; 123: 11-14.
71. DiNicolantonio JJ, Serebruany VL: Exploring the reduction in myocardial infarctions in the PLATO trial: which patients benefited on ticagrelor vs clopidogrel Int J Cardiol 2013; 165: 396-397.
72. Singh A, Fingerhood M, Feit F, Bangalore S: Does triple therapy with cilostazol reduce the risk of restenosis in patients undergoing percutaneous coronary intervention Insights from a meta-analysis of randomized clinical trials. J Am Coll Cardiol 2012; 59:e501.
73. Singh A, Feit F, Bangalore S: Does triple therapy with cilostazol decrease platelet reactivity in patients undergoing percutaneous coronary intervention A meta-analysis of randomized clinical trials. J Am Coll Cardiol 2012; 59:E527.
74. Perret-Guillaume C, Joly L, Benetos A: Heart rate as a risk factor for cardiovascular disease. Prog Cardiovasc Dis 2009; 52: 6-10.
75. 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, for the 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.
76. Meier P, Lansky AJ: Optimal duration of clopidogrel therapy: the shorter the longer Eur Heart J 2013; 34: 1705-1707.
77. Cassese S, Byrne RA, Tada T, King LA, Kastrati A: Clinical impact of extended dual antiplatelet therapy after percutaneous coronary interventions in the drug-eluting stent era: a meta-analysis of randomized trials. Eur Heart J 2012; 33: 3078-3087.
78. Suh JW, Lee SP, Park KW, Lee HY, Kang HJ, Koo BK, Cho YS, Youn TJ, Chae IH, Choi DJ, Rha SW, Bae JH, Kwon TG, Bae JW, Cho MC, Kim HS: Multicenter randomized trial evaluating the efficacy of cilostazol on ischemic vascular complications after drug-eluting stent implantation for coronary heart disease: results of the CILON-T (influence of CILostazol-based triple antiplatelet therapy ON ischemic complication after drug-eluting stenT implantation) trial. J Am Coll Cardiol 2011; 57: 280-289.