Korean Circ J.  2009 May;39(5):190-197. 10.4070/kcj.2009.39.5.190.

Efficacy of Triple Anti-Platelet Therapy Including Cilostazol in Acute Myocardial Infarction Patients Undergoing Drug-Eluting Stent Implantation

• Park KH
• Jeong MH
• Lee MG
• Ko JS
• Lee SE
• Kang WY
• Kim SH
• Sim DS
• Yoon NS
• Youn HJ
• Hong YJ
• Park HW
• Kim JH
• Ahn Y
• Cho JG
• Park JC
• Kang JC

• KMID: 1826018
• DOI: http://doi.org/10.4070/kcj.2009.39.5.190

Abstract

BACKGROUND AND OBJECTIVES: Triple anti-platelet therapy is known to prevent restenosis after drug-eluting stent (DES) implantation. However, there is little available data concerning the efficacy of triple anti-platelet therapy for acute myocardial infarction (AMI).
SUBJECTS AND METHODS
We analyzed 528 consecutive patients with AMI undergoing DES implantation between Nov 2005 and Apr 2008. We compared clinical outcomes in the triple anti-platelet therapy (group I, n=413: cilostazol combined with aspirin and clopidogrel for at least one month) and dual antiplatelet therapy groups (group II, n=115: aspirin and clopidogrel).
RESULTS
There were no significant differences in baseline characteristics. However, ST elevation myocardial infarction (STEMI) and use of TAXUS(R) stents were more common (70.9% vs. 55.7%, p=0.002; 83.5% vs. 73.0%, p=0.011) in Group I. Group I had lower incidences of cardiac death, 6-month target lesion revascularization (TLR), and major adverse cardiac and cerebrovascular events (MACCE) compared to Group II (1.7% vs. 5.7%, p=0.022; 5.7% vs. 11.5%, 0.035; 7.9% vs. 16.0%, p=0.011). On subgroup analysis, the incidence of 6-month TLR was lower among patients with American College of Cardiology/American Heart Association (ACC/AHA) B2 or C lesions and non-STEMI (6.0% vs. 14.9%, p=0.012; 4.3% vs. 19.1%, p=0.002) in Group I compared to those in Group II. The rates of bleeding complications were no different between the two groups. On multivariate analysis, Killip III or IV and triple anti-platelet therapy were independent predictors of 6-month MACCE {hazard ratio (HR)=3.382; 95% confidence interval (CI)=1.384-8.262, HR=0.436; 95% CI=0.203-0.933}.
CONCLUSION
Triple anti-platelet therapy is safe and efficacious, and it prevents TLR in patients with AMI, especially those with complex lesions and non-STEMIs.

Keyword

Platelets; Drug-eluting stents; Myocardial infarction

MeSH Terms

Aspirin
Blood Platelets
Death
Drug-Eluting Stents
Heart
Hemorrhage
Humans
Incidence
Multivariate Analysis
Myocardial Infarction
Stents
Tetrazoles
Ticlopidine
Aspirin
Tetrazoles
Ticlopidine

Reference

1. Lee SR, Jeong MH, Ahn YK, et al. Clinical safety of drug-eluting stents in the Korea acute myocardial infarction registry. Circ J. 2008. 72:392–398.

2. Pasceri V, Patti G, Speciale G, Pristipino C, Richichi G, Di Sciascio G. Meta-analysis of clinical trials on use of drug-eluting stents for treatment of acute myocardial infarction. Am Heart J. 2007. 153:749–754.

3. Melikian N, Wijns W. Drug-eluting stents: a critique. Heart. 2008. 94:145–152.

4. Antman EM, Hand M, Armstrong PW, et al. 2007 Focused update of the ACC/AHA 2004 guidelines for the management of patients with ST-elevation myocardial infarction: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines: developed in collaboration with the Canadian Cardiovascular Society endorsed by the American Academy of Family Physicians: 2007 writing group to review new evidence and update the ACC/AHA 2004 guidelines for the management of patients with ST-elevation myocardial infarction, writing on behalf of the 2004 writing committee. Circulation. 2008. 117:296–329.

5. Goto S. Cilostazol: potential mechanism of action for antithrombotic effects accompanied by a low rate of bleeding. Atheroscler Suppl. 2005. 6:3–11.

6. Douglas JS Jr. Role of adjunct pharmacologic therapy in the era of drug-eluting stents. Atheroscler Suppl. 2005. 6:47–52.

7. Douglas JS Jr, Holmes DR Jr, Kereiakes DJ, et al. Coronary stent restenosis in patients treated with cilostazol. Circulation. 2005. 112:2826–2832.

8. Lee SW, Park SW, Hong MK, et al. Triple versus dual antiplatelet therapy after coronary stenting: impact on stent thrombosis. J Am Coll Cardiol. 2005. 46:1833–1837.

9. Ahn Y, Jeong MH, Jeong JW, et al. Randomized comparison of cilostazol vs clopidogrel after drug-eluting stenting in diabetic patients: clilostazol for diabetic patients in drug-eluting stent (CIDES) trial. Circ J. 2008. 72:35–39.

10. Lee SW, Park SW, Kim YH, et al. Drug-eluting stenting followed by cilostazol treatment reduces late restenosis in patients with diabetes mellitus the DECLARE-DIABETES Trial (A Randomized Comparison of Triple Antiplatelet Therapy with Dual Antiplatelet Therapy After Drug-Eluting Stent Implantation in Diabetic Patients). J Am Coll Cardiol. 2008. 51:1181–1187.

11. Mauri L, Hsieh WH, Massaro JM, Ho KK, D'Agostino R, Cutlip DE. Stent thrombosis in randomized clinical trials of drug-eluting stents. N Engl J Med. 2007. 356:1020–1029.

12. Rao AK, Pratt C, Berke A, et al. Thrombolysis in Myocardial Infarction (TIMI) Trial: phase I. hemorrhagic manifestations and changes in plasma fibrinogen and the fibrinolytic system in patients treated with recombinant tissue plasminogen activator and streptokinase. J Am Coll Cardiol. 1988. 11:1–11.

13. Mauri L, Silbaugh TS, Garg P, et al. Drug-eluting or bare-metal stents for acute myocardial infarction. N Engl J Med. 2008. 359:1330–1342.

14. Nakazawa G, Finn AV, Joner M, et al. Delayed arterial healing and increased late stent thrombosis at culprit sites after drug-eluting stent placement for acute myocardial infarction: an autopsy study. Circulation. 2008. 118:1138–1145.

15. Stone GW, Moses JW, Ellis SG, et al. Safety and efficacy of sirolimus- and paclitaxel-eluting coronary stents. N Engl J Med. 2007. 356:998–1008.

16. Kim W, Jeong MH, Kim KH, et al. The clinical results of a platelet glycoprotein IIb/IIIa receptor blocker (abciximab: ReoPro)-coated stent in acute myocardial infarction. J Am Coll Cardiol. 2006. 47:933–938.

17. Mitka M. New drug-eluting stents under study. JAMA. 2007. 297:2064–2067.

18. Mehta SR, Yusuf S, Peters RJ, et al. 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.

19. Yusuf S, Zhao F, Mehta SR, Chrolavicius S, Tognoni G, Fox KK. 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.

20. Tanaka T, Ishikawa T, Hagiwara M, Onoda K, Itoh H, Hidaka H. Effects of cilostazol, a selective cAMP phosphodiesterase inhibitor on the contraction of vascular smooth muscle. Pharmacology. 1988. 36:313–320.

21. Chu YH, Park SW, Lee CW, et al. Effects of cilostazol treatment on angiographic restenosis after coronary stent placement. Korean Circ J. 2000. 30:1494–1500.

22. Ikeda Y, Kikuchi M, Murakami H, et al. Comparison of the inhibitory effects of cilostazol, acetylsalicylic acid and ticlopidine on platelet functions ex vivo: randomized, double-blind cross-over study. Arzneimittelforschung. 1987. 37:563–566.

23. Ahn JC, Song WH, Kwon JA, et al. Effects of cilostazol on platelet activation in coronary stenting patients who already treated with aspirin and clopidogrel. Korean J Intern Med. 2004. 19:230–236.

24. Kim SM, Kim DI, Cho HJ, et al. Effect of cilostazol on the drug-eluting stent in native coronary arteries. Korean Circ J. 2007. 37:304–311.

25. 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.

26. Lee KJ, Yun SW, Kim SW, Kim TH, Kim CJ, Ryu WS. The effect of cilostazol on proliferation of vascular smooth muscle cells and expression of iNOS and p21. Korean Cir J. 2004. 34:500–506.

27. Morishita R. A scientific rationale for the CREST trial results: evidence for the mechanism of action of cilostazol in restenosis. Atheroscler Suppl. 2005. 6:41–46.

28. Lee SW, Park SW, Kim YH, et al. Comparison of triple versus dual antiplatelet therapy after drug-eluting stent implantation (from the DECLARE-Long trial). Am J Cardiol. 2007. 100:1103–1108.

29. Viles-Gonzalez JF, Fuster V, Badimon JJ. Atherothrombosis: a widespread disease with unpredictable and life-threatening consequences. Eur Heart J. 2004. 25:1197–1207.

30. Ong AT, Hoye A, Aoki J, et al. Thirty-day incidence and six-month clinical outcome of thrombotic stent occlusion after baremetal, sirolimus, or paclitaxel stent implantation. J Am Coll Cardiol. 2005. 45:947–953.