Efficacy and Safety of Triple Antiplatelet Therapy for Patients with Coronary Heart Diseases after Percutaneous Coronary Intervention: A Meta-Analysis_Chinese Journal of Evidence-Based Medicine

Authors：

 DANGLin-lin ¹ , YAOYa-li ² , LINRui-jiang ¹

1. First Clinical Medical College of Lanzhou University, Lanzhou 730000, China;
2. First Affiliated Hospital of Lanzhou University, Lanzhou 730000, China;

Corresponding author：

Keywords：

Triple antiplatelet therapy; Percutaneous coronary intervention; Coronary heart disease; Systematic review; Meta-analysis; Randomized controlled trial

DOI：

10.7507/1672-2531.20140218

Video：

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Objective To systematically review the efficacy and safety of triple antiplatelet therapy (TAT:aspirin, clopidogrel and cilostazol) for patients with coronary heart diseases after percutaneous coronary intervention. Methods Such databases as The Cochrane Library (Issue 2, 2014), PubMed, EMbase, Web of Science, CBM, CNKI, VIP and WanFang Data were electronically searched for relevant randomized controlled trials (RCTs) on the efficacy and safety of TAT for patients with coronary heart diseases after percutaneous coronary intervention from inception to February 2014. Two reviewers independently screened literature according to inclusion and exclusion criteria, extracted data, and assessed methodological quality of included studies. Then meta-analysis was performed using RevMan 5.2 software. Results A total of 15 RCTs involved 6 980 patients were included. The results of meta-analysis showed that:a) the DAT group (DAT:aspirin and clopidogrel) and the TAT group were similar in non-fatal myocardial infarction (OR=0.72, 95%CI 0.47 to 1.10, P=0.05), stroke (OR=0.66, 95%CI 0.38 to 1.16, P=0.15), and hemorrhage (OR=1.03, 95%CI 0.74 to 1.44, P=0.85) with no significant difference; b) the TAT group was superior to the DAT group in reducing the incidences of the major cardiovascular and cerebrovascular events (MACCE) (OR=0.50, 95%CI 0.39 to 0.65, P < 0.000 01), cardiac death (OR=0.53, 95%CI 0.33 to 0.84, P=0.007), stent thrombosis (OR=0.52, 95% CI 0.27 to 0.99, P=0.05), target vessel revascularization (OR=0.63, 95%CI 0.51 to 0.76, P < 0.000 01), and target lesion revascularization (OR=0.44, 95%CI 0.28 to 0.70, P=0.000 6); and c) no significant difference was found between the two groups in the incidences of thrombocytopenia, leucopenia, and liver damage. The DAT group was superior to the TAT group in gastrointestinal reaction, palpitations, headache, and skin rashes between the two groups, with significant differences. Conclusion TAT therapy has good efficacy and safety in the treatment of patients with coronary heart diseases after percutaneous coronary intervention.

Citation： DANGLin-lin, YAOYa-li, LINRui-jiang. Efficacy and Safety of Triple Antiplatelet Therapy for Patients with Coronary Heart Diseases after Percutaneous Coronary Intervention: A Meta-Analysis. Chinese Journal of Evidence-Based Medicine, 2014, 14(11): 1351-1360. doi: 10.7507/1672-2531.20140218 Copy

1.	Aradi D, Komócsi A, Price MJ, et al. Efficacy and safety of intensified antiplatelet therapy on the basis of platelet reactivity testing in patients after percutaneous coronary intervention:Systematic review and meta analysis. Int J Cardiol, 2013, 167(5):2140-2148.
2.	Meryon I, Patel N, Millane T, et al. Normal coronary angiography and primary percutaneous coronary intervention for ST elevation myocardial infarction:a literature review and audit findings. Int J Clin Pract, 2010, 64:1245-1251.
3.	刘迎午, 彭文近, 刘博江, 等.支架断裂并发急性血栓形成2例救治体会.中国医药导报, 2011, (21):1673.
4.	Meier B, Bachmann D, Lüscher T, et al. 25 years of coronary angioplasty:almost a fairy tale. Lancet, 2003, 361(9356):527.
5.	Mrdovic I, Savic L, Lasica R, et al. Usefulness of the RISK-PCI score to predict stent thrombosis in patients treated with primary percutaneous coronary intervention for ST-segment elevation myocardial infarction:a substudy of the RISK-PCI trial. Heart Vessels, 2013, 28:424-433.
6.	Gurbel PA, Tantry US. Aspirin and clopidogrel resistance:consideration and management. J Interv Cardiol, 2006, 19:439-448.
7.	Takahashi S, Kaneda H, Tanaka S, et al. Late angiographic stent thrombosis after sirolimus-eluting stent implantation. Circ J, 2009, 71:226-228.
8.	Regensteiner JG, Stewart KJ. Established and evolving medical therapies for claudication in patients with peripheral arterial disease. Nat Clin Pract Cardiovasc Med, 2006, 3:604-610.
9.	Jeong YH, Lee SW, Choi BR, et al. Randomized comparison of adjunctive cilostazol versus high maintenance dose clopidogrel in patients with high post-treatment platelet reactivity:results of the ACCEL-RESISTANCE (Adjunctive Cilostazol Versus High Maintenance Dose Clopidogrel in Patients with Clopidogrel Resistance) randomized study. J Am Coll Cardiol, 2009, 53:1101-1109.
10.	阮家兰.经皮冠状动脉介入治疗术后不同抗血小板治疗方案疗效对比.中国医药导报, 2012, 9(27):66-70.
11.	孟利敏, 孟英杰, 孙永锋, 等.冠状动脉支架术后个体化抗血小板治疗的临床疗效观察.临床荟萃, 2010, 25(24):2149-2152.
12.	沈峻, 金惠根, 刘宗军, 等.急性冠状动脉综合征合并糖尿病患者药物涂层支架术后三联抗血小板药物应用的远期效果.上海医学, 2010, 33(6):566-569.
13.	臧红云, 韩雅玲, 李毅, 等.糖尿病患者冠状动脉介入治疗术后三联抗血小板治疗的长期疗效.解放军医学杂志, 2008, 33(8):931-934.
14.	Gao W, Zhang Q, Ge H, et al. Efficacy and safety of triple antiplatelet therapy in obese patients undergoing stent implantation. Angilogy, 2013, 64:554-558.
15.	芦燕玲, 陈韵岱, 吕树铮, 等.西洛他哇预防老年冠心病患者冠状动脉金属裸支架术后再狭窄的疗效.中国老年医学杂志, 2006, 25(7):537-538.
16.	Suh JW, Lee SP, Park KW, et al. 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.
17.	Douglas JS, Holmes DR, Kereiakes DJ, et al. Coronary stent restenosis in patients treated with cilostazol. Circulation, 2005, 112:2826-2832.
18.	Lee SW, Chun KJ, Park SW, et al. Comparison of triple antiplatelet therapy and dual antiplatelet therapy in patients at high risk of restenosis after drug-eluting stent implantation (from the DECLARE-DIABETES and-LONG trials). Am J Cardiol, 2010, 105:168-173.
19.	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.
20.	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. JACC Cardiovasc interv, 2011, 57:1264-1270.
21.	Chen YD, Lu YL, Jin ZN, et al. A prospective randomized antiplatelet trial of cilostazol versus clopidogrel in patients with bare metal stent. Chin Med J, 2006, 119:360-366.
22.	Ahn CM, Hong SJ, Park JH, et al. Cilostazol reduces the progression of carotid intima-media thickness without increasing the risk of bleeding in patients with acute coronary syndrome during a 2-year follow-up. Heart Vessels, 2011, 26:502-510.
23.	芦燕玲, 陈韵岱, 吕树铮.经皮冠状动脉介入治疗后血小板聚集率高的患者强化抗血小板治疗的研究.中华心血管病杂志, 2007, 35(9):793-796.
24.	田锐, 吕树铮, 柳弘, 等.老年人药物洗脱支架置人术后应用西洛他唑的疗效和安全性. 2012, 31(3):185-188.
25.	Smith SC Jr, Dove JT, Jacobs AK, et al. ACC/AHA guidelines for percutaneous coronary intervention (revision of the 1993 PTCA guidelines)-executive summary:a report of the American College of Cardiology/American Heart Association task force on practice guidelines (Committee to revise the 1993 guidelines for percutaneous transluminal coronary angioplasty) endorsed by the Society for Cardiac Angiography and Interventions. Circulation, 2001, 103:3019-3041.
26.	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 randomized controlled trials. Euro Intervention, 2009, 5:384-393.
27.	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.
28.	Schömig A, Neumann FJ, Kastrati A, et al. A randomized comparison of antiplatelet and anticoagulant therapy after the placement of coronary-artery stents. N Engl J Med, 1996, 334:1084-1089.
29.	Han YL, Su QF, Li Y, et al. The effects of post coronary stenting triple antiplatelet therapies on platelet functions. Chin J Int Med, 2006, 45:635-638.
30.	Sun FC, Deng KB. Antiplatelet therapy in patients post percutaneous coronary stent implantion. Chin J Cardiovasc Med, 2003, 8:369-371.
31.	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.
32.	Takagi H, Umemoto T. A meta-analysis of randomized trials of triple versus dual antiplatelet therapy after stent-based percutaneous coronary intervention. Int J Cardiol, 2011, 150:228-230.
33.	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.
34.	Tanigawa T, Nishikawa M, Kitai T, et al. Increased platelet aggregability in response to shear in acute myocardial infarction and its inhibition by combined therapy with aspirin and cilostazolafter coronary intervention. Am J Cardiol, 2000, 85(3):1054-1059.
35.	Berger PB. Clopidogrel instead of ticlopidine after coronary stent placement:is the switch justified? Am Heart J, 2000, 140(3):354-358.
36.	Calver AL, Blows LJ, Harmer S, et al. Clopidogrel for prevention of major cardiac events after coronary stent implantation:30-day and 6-month results in patients with smaller stenta. Am Heart J, 2000, 140(3):483-491.
37.	Wang P, Zhou S, Zhou R, et al. The effectiveness and safety of triple-antiplatelet treatment based on cilostazol for patients receiving percutaneous coronary intervention:a meta-analysis. Clinical cardiology, 2012, 35(10):598-604.
38.	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. Euro Intervention, 2009, 5(3):384-393.

1. Aradi D, Komócsi A, Price MJ, et al. Efficacy and safety of intensified antiplatelet therapy on the basis of platelet reactivity testing in patients after percutaneous coronary intervention:Systematic review and meta analysis. Int J Cardiol, 2013, 167(5):2140-2148.
2. Meryon I, Patel N, Millane T, et al. Normal coronary angiography and primary percutaneous coronary intervention for ST elevation myocardial infarction:a literature review and audit findings. Int J Clin Pract, 2010, 64:1245-1251.
3. 刘迎午, 彭文近, 刘博江, 等.支架断裂并发急性血栓形成2例救治体会.中国医药导报, 2011, (21):1673.
4. Meier B, Bachmann D, Lüscher T, et al. 25 years of coronary angioplasty:almost a fairy tale. Lancet, 2003, 361(9356):527.
5. Mrdovic I, Savic L, Lasica R, et al. Usefulness of the RISK-PCI score to predict stent thrombosis in patients treated with primary percutaneous coronary intervention for ST-segment elevation myocardial infarction:a substudy of the RISK-PCI trial. Heart Vessels, 2013, 28:424-433.
6. Gurbel PA, Tantry US. Aspirin and clopidogrel resistance:consideration and management. J Interv Cardiol, 2006, 19:439-448.
7. Takahashi S, Kaneda H, Tanaka S, et al. Late angiographic stent thrombosis after sirolimus-eluting stent implantation. Circ J, 2009, 71:226-228.
8. Regensteiner JG, Stewart KJ. Established and evolving medical therapies for claudication in patients with peripheral arterial disease. Nat Clin Pract Cardiovasc Med, 2006, 3:604-610.
9. Jeong YH, Lee SW, Choi BR, et al. Randomized comparison of adjunctive cilostazol versus high maintenance dose clopidogrel in patients with high post-treatment platelet reactivity:results of the ACCEL-RESISTANCE (Adjunctive Cilostazol Versus High Maintenance Dose Clopidogrel in Patients with Clopidogrel Resistance) randomized study. J Am Coll Cardiol, 2009, 53:1101-1109.
10. 阮家兰.经皮冠状动脉介入治疗术后不同抗血小板治疗方案疗效对比.中国医药导报, 2012, 9(27):66-70.
11. 孟利敏, 孟英杰, 孙永锋, 等.冠状动脉支架术后个体化抗血小板治疗的临床疗效观察.临床荟萃, 2010, 25(24):2149-2152.
12. 沈峻, 金惠根, 刘宗军, 等.急性冠状动脉综合征合并糖尿病患者药物涂层支架术后三联抗血小板药物应用的远期效果.上海医学, 2010, 33(6):566-569.
13. 臧红云, 韩雅玲, 李毅, 等.糖尿病患者冠状动脉介入治疗术后三联抗血小板治疗的长期疗效.解放军医学杂志, 2008, 33(8):931-934.
14. Gao W, Zhang Q, Ge H, et al. Efficacy and safety of triple antiplatelet therapy in obese patients undergoing stent implantation. Angilogy, 2013, 64:554-558.
15. 芦燕玲, 陈韵岱, 吕树铮, 等.西洛他哇预防老年冠心病患者冠状动脉金属裸支架术后再狭窄的疗效.中国老年医学杂志, 2006, 25(7):537-538.
16. Suh JW, Lee SP, Park KW, et al. 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.
17. Douglas JS, Holmes DR, Kereiakes DJ, et al. Coronary stent restenosis in patients treated with cilostazol. Circulation, 2005, 112:2826-2832.
18. Lee SW, Chun KJ, Park SW, et al. Comparison of triple antiplatelet therapy and dual antiplatelet therapy in patients at high risk of restenosis after drug-eluting stent implantation (from the DECLARE-DIABETES and-LONG trials). Am J Cardiol, 2010, 105:168-173.
19. 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.
20. 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. JACC Cardiovasc interv, 2011, 57:1264-1270.
21. Chen YD, Lu YL, Jin ZN, et al. A prospective randomized antiplatelet trial of cilostazol versus clopidogrel in patients with bare metal stent. Chin Med J, 2006, 119:360-366.
22. Ahn CM, Hong SJ, Park JH, et al. Cilostazol reduces the progression of carotid intima-media thickness without increasing the risk of bleeding in patients with acute coronary syndrome during a 2-year follow-up. Heart Vessels, 2011, 26:502-510.
23. 芦燕玲, 陈韵岱, 吕树铮.经皮冠状动脉介入治疗后血小板聚集率高的患者强化抗血小板治疗的研究.中华心血管病杂志, 2007, 35(9):793-796.
24. 田锐, 吕树铮, 柳弘, 等.老年人药物洗脱支架置人术后应用西洛他唑的疗效和安全性. 2012, 31(3):185-188.
25. Smith SC Jr, Dove JT, Jacobs AK, et al. ACC/AHA guidelines for percutaneous coronary intervention (revision of the 1993 PTCA guidelines)-executive summary:a report of the American College of Cardiology/American Heart Association task force on practice guidelines (Committee to revise the 1993 guidelines for percutaneous transluminal coronary angioplasty) endorsed by the Society for Cardiac Angiography and Interventions. Circulation, 2001, 103:3019-3041.
26. 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 randomized controlled trials. Euro Intervention, 2009, 5:384-393.
27. 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.
28. Schömig A, Neumann FJ, Kastrati A, et al. A randomized comparison of antiplatelet and anticoagulant therapy after the placement of coronary-artery stents. N Engl J Med, 1996, 334:1084-1089.
29. Han YL, Su QF, Li Y, et al. The effects of post coronary stenting triple antiplatelet therapies on platelet functions. Chin J Int Med, 2006, 45:635-638.
30. Sun FC, Deng KB. Antiplatelet therapy in patients post percutaneous coronary stent implantion. Chin J Cardiovasc Med, 2003, 8:369-371.
31. 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.
32. Takagi H, Umemoto T. A meta-analysis of randomized trials of triple versus dual antiplatelet therapy after stent-based percutaneous coronary intervention. Int J Cardiol, 2011, 150:228-230.
33. 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.
34. Tanigawa T, Nishikawa M, Kitai T, et al. Increased platelet aggregability in response to shear in acute myocardial infarction and its inhibition by combined therapy with aspirin and cilostazolafter coronary intervention. Am J Cardiol, 2000, 85(3):1054-1059.
35. Berger PB. Clopidogrel instead of ticlopidine after coronary stent placement:is the switch justified? Am Heart J, 2000, 140(3):354-358.
36. Calver AL, Blows LJ, Harmer S, et al. Clopidogrel for prevention of major cardiac events after coronary stent implantation:30-day and 6-month results in patients with smaller stenta. Am Heart J, 2000, 140(3):483-491.
37. Wang P, Zhou S, Zhou R, et al. The effectiveness and safety of triple-antiplatelet treatment based on cilostazol for patients receiving percutaneous coronary intervention:a meta-analysis. Clinical cardiology, 2012, 35(10):598-604.
38. 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. Euro Intervention, 2009, 5(3):384-393.

Chinese Journal of Evidence-Based Medicine

Efficacy and Safety of Triple Antiplatelet Therapy for Patients with Coronary Heart Diseases after Percutaneous Coronary Intervention: A Meta-Analysis

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