Clopidogrel discontinuation within the first year after coronary drug-eluting stent implantation: an observational study

BMC Cardiovascular Disorders

Michael Maeng³  Hans-Henrik Tilsted⁴  Lisette Okkels Jensen¹  Per Thayssen¹  Jens Flensted Lassen³  Lars Romer Krusell³  Hans Erik Bøtker²  Steen Dalby Kristensen³  Leif Thuesen³  Henrik Toft Sørensen²  Anne Kaltoft³  Morten Schmidt²  Gro Egholm Chisholm³  Martin Berg Johansen²  Troels Thim³ 

[1] Department of Cardiology, Odense University Hospital, Odense, Denmark;Department of Clinical Epidemiology, Aarhus University Hospital, Brendstrupgaardsvej 100, Aarhus, N 8200, Denmark;Department of Cardiology, Aarhus University Hospital, Aarhus, Denmark;Department of Cardiology, Aalborg University Hospital, Aalborg, Denmark

关键词: Clopidogrel;    Drug-eluting stent;    Dual antiplatelet therapy;    Percutaneous coronary intervention;   

Others  :  1088472
DOI  :  10.1186/1471-2261-14-100

 received in 2014-05-04, accepted in 2014-08-01,  发布年份 2014

【 摘 要 】

Background

The impact of adherence to the recommended duration of dual antiplatelet therapy after first generation drug-eluting stent implantation is difficult to assess in real-world settings and limited data are available.

Methods

We followed 4,154 patients treated with coronary drug-eluting stents in Western Denmark for 1 year and obtained data on redeemed clopidogrel prescriptions and major adverse cardiovascular events (MACE, i.e., cardiac death, myocardial infarction, or stent thrombosis) from medical databases.

Results

Discontinuation of clopidogrel within the first 3 months after stent implantation was associated with a significantly increased rate of MACE at 1-year follow-up (hazard ratio (HR) 2.06; 95% confidence interval (CI): 1.08-3.93). Discontinuation 3-6 months (HR 1.29; 95% CI: 0.70-2.41) and 6-12 months (HR 1.29; 95% CI: 0.54-3.07) after stent implantation were associated with smaller, not statistically significant, increases in MACE rates. Among patients who discontinued clopidogrel, MACE rates were highest within the first 2 months after discontinuation.

Conclusions

Discontinuation of clopidogrel was associated with an increased rate of MACE among patients treated with drug-eluting stents. The increase was statistically significant within the first 3 months after drug-eluting stent implantation but not after 3 to 12 months.

【 授权许可】

   
2014 Thim et al.; licensee BioMed Central Ltd.

【 图 表 】

Figure 1.

Figure 2.

Figure 3.

【 参考文献 】

• [1]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.
• [2]Steinhubl SR, Berger PB, Mann JT III, Fry ET, DeLago A, Wilmer C, Topol EJ: Early and sustained dual oral antiplatelet therapy following percutaneous coronary intervention: a randomized controlled trial. JAMA 2002, 288:2411-2420.
• [3]Kleiman NS: Grabbing the horns of a dilemma: the duration of dual antiplatelet therapy after stent implantation. Circulation 2012, 125:1967-1970.
• [4]Sørensen HT: Regional administrative health registries as a resource in clinical epidemiology. Int J Risk Saf Med 1997, 10:1-22.
• [5]Andersen TF, Madsen M, Jorgensen J, Mellemkjoer L, Olsen JH: The Danish National Hospital Register. A valuable source of data for modern health sciences. Dan Med Bull 1999, 46:263-268.
• [6]Juel K, Helweg-Larsen K: The Danish registers of causes of death. Dan Med Bull 1999, 46:354-357.
• [7]Frank L: Epidemiology. When an entire country is a cohort. Science 2000, 287:2398-2399.
• [8]Madsen M, Davidsen M, Rasmussen S, Abildstrom SZ, Osler M: The validity of the diagnosis of acute myocardial infarction in routine statistics: a comparison of mortality and hospital discharge data with the Danish MONICA registry. J Clin Epidemiol 2003, 56:124-130.
• [9]Pedersen CB, Gotzsche H, Moller JO, Mortensen PB: The Danish Civil Registration System. A cohort of eight million persons. Dan Med Bull 2006, 53:441-449.
• [10]Schmidt M, Maeng M, Jakobsen CJ, Madsen M, Thuesen L, Nielsen PH, Botker HE, Sorensen HT: Existing data sources for clinical epidemiology: the Western Denmark Heart Registry. Clin Epidemiol 2010, 2:137-144.
• [11]Jensen LO, Tilsted HH, Thayssen P, Kaltoft A, Maeng M, Lassen JF, Hansen KN, Madsen M, Ravkilde J, Johnsen SP, Sørensen HT, Thuesen L: Paclitaxel and sirolimus eluting stents versus bare metal stents: long-term risk of stent thrombosis and other outcomes. From the Western Denmark Heart Registry. EuroIntervention 2010, 5:898-905.
• [12]Kaltoft A, Jensen LO, Maeng M, Tilsted HH, Thayssen P, Bottcher M, Lassen JF, Krusell LR, Rasmussen K, Hansen KN, Pedersen L, Johnsen SP, Sørensen HT, Thuesen L: 2-year clinical outcomes after implantation of sirolimus-eluting, paclitaxel-eluting, and bare-metal coronary stents: results from the WDHR (Western Denmark Heart Registry). J Am Coll Cardiol 2009, 53:658-664.
• [13]Jensen LO, Maeng M, Kaltoft A, Thayssen P, Hansen HH, Bottcher M, Lassen JF, Krussel LR, Rasmussen K, Hansen KN, Pedersen L, Johnsen SP, Soerensen HT, Thuesen L: Stent thrombosis, myocardial infarction, and death after drug-eluting and bare-metal stent coronary interventions. J Am Coll Cardiol 2007, 50:463-470.
• [14]Wallach Kildemoes H, Toft Sørensen H, Hallas J: The Danish National Prescription Registry. Scand J Public Health 2011, 39:38-41.
• [15]Schmidt M, Johansen MB, Robertson DJ, Maeng M, Kaltoft A, Jensen LO, Tilsted HH, Botker HE, Sorensen HT, Baron JA: Use of clopidogrel and calcium channel blockers and risk of major adverse cardiovascular events. Eur J Clin Invest 2012, 42:266-274.
• [16]Schmidt M, Johansen MB, Robertson DJ, Maeng M, Kaltoft A, Jensen LO, Tilsted HH, Botker HE, Sorensen HT, Baron JA: Concomitant use of clopidogrel and proton pump inhibitors is not associated with major adverse cardiovascular events following coronary stent implantation. Aliment Pharmacol Ther 2012, 35:165-174.
• [17]Schmidt M, Johansen MB, Maeng M, Kaltoft A, Jensen LO, Tilsted HH, Botker HE, Baron JA, Sorensen HT: Concomitant use of clopidogrel and statins and risk of major adverse cardiovascular events following coronary stent implantation. Br J Clin Pharmacol 2012, 74:161-170.
• [18]Ko DT, Chiu M, Guo H, Austin PC, Marquis JF, Tu JV: Patterns of use of thienopyridine therapy after percutaneous coronary interventions with drug-eluting stents and bare-metal stents. Am Heart J 2009, 158:592-598.
• [19]Cutlip DE, Windecker S, Mehran R, Boam A, Cohen DJ, van Es GA, Steg PG, Morel MA, Mauri L, Vranckx P, McFadden E, Lansky A, Hamon M, Krucoff MW, Serruys PW, Academic Research Consortium: Clinical end points in coronary stent trials: a case for standardized definitions. Circulation 2007, 115:2344-2351.
• [20]Spertus JA, Kettelkamp R, Vance C, Decker C, Jones PG, Rumsfeld JS, Messenger JC, Khanal S, Peterson ED, Bach RG, Krumholz HM, Cohen DJ: Prevalence, predictors, and outcomes of premature discontinuation of thienopyridine therapy after drug-eluting stent placement: results from the PREMIER registry. Circulation 2006, 113:2803-2809.
• [21]Rossini R, Capodanno D, Lettieri C, Musumeci G, Nijaradze T, Romano M, Lortkipanidze N, Cicorella N, Biondi ZG, Sirbu V, Izzo A, Guagliumi G, Valsecchi O, Gavazzi A, Angiolillo DJ: Prevalence, predictors, and long-term prognosis of premature discontinuation of oral antiplatelet therapy after drug eluting stent implantation. Am J Cardiol 2011, 107:186-194.
• [22]Kimura T, Morimoto T, Nakagawa Y, Tamura T, Kadota K, Yasumoto H, Nishikawa H, Hiasa Y, Muramatsu T, Meguro T, Inoue N, Honda H, Hayashi Y, Miyazaki S, Oshima S, Honda T, Shiode N, Namura M, Sone T, Nobuyoshi M, Kita T, Mitsudo K, j-Cypher Registry Investigators: Antiplatelet therapy and stent thrombosis after sirolimus-eluting stent implantation. Circulation 2009, 119:987-995.
• [23]Ferreira-Gonzalez I, Marsal JR, Ribera A, Permanyer-Miralda G, Garcia-Del BB, Marti G, Cascant P, Martin-Yuste V, Brugaletta S, Sabate M, Alfonso F, Capote ML, De La Torre JM, Ruíz-Lera M, Sanmiguel D, Cárdenas M, Pujol B, Baz JA, Iñiguez A, Trillo R, González-Béjar O, Casanova J, Sánchez-Gila J, García-Dorado D: Background, incidence, and predictors of antiplatelet therapy discontinuation during the first year after drug-eluting stent implantation. Circulation 2010, 122:1017-1025.
• [24]Ferreira-Gonzalez I, Marsal JR, Ribera A, Permanyer-Miralda G, Garcia-Del BB, Marti G, Cascant P, Masotti-Centol M, Carrillo X, Mauri J, Batalla N, Larrousse E, Martín E, Serra A, Rumoroso JR, Ruiz-Salmerón R, de la Torre JM, Cequier A, Gómez-Hospital JA, Alfonso F, Martín-Yuste V, Sabatè M, García-Dorado D: Double antiplatelet therapy after drug-eluting stent implantation: risk associated with discontinuation within the first year. J Am Coll Cardiol 2012, 60:1333-1339.
• [25]Roy P, Bonello L, Torguson R, Okabe T, Pinto Slottow TL, Steinberg DH, Kaneshige K, Xue Z, Satler LF, Kent KM, Suddath WO, Pichard AD, Lindsay J, Waksman R: Temporal relation between Clopidogrel cessation and stent thrombosis after drug-eluting stent implantation. Am J Cardiol 2009, 103:801-805.
• [26]Mehran R, Baber U, Steg PG, Ariti C, Weisz G, Witzenbichler B, Henry TD, Kini AS, Stuckey T, Cohen DJ, Berger PB, Iakovou I, Dangas G, Waksman R, Antoniucci D, Sartori S, Krucoff MW, Hermiller JB, Shawl F, Gibson CM, Chieffo A, Alu M, Moliterno DJ, Colombo A, Pocock S: Cessation of dual antiplatelet treatment and cardiac events after percutaneous coronary intervention (PARIS): 2 year results from a prospective observational study. Lancet 2013, 382:1714-1722.
• [27]Shin DH, Chae IH, Youn TJ, Cho SI, Kwon DA, Suh JW, Chang HJ, Cho YS, Chung WY, Choi YJ, Gwon HC, Han KR, Choi DJ: Reasonable duration of Clopidogrel use after drug-eluting stent implantation in Korean patients. Am J Cardiol 2009, 104:1668-1673.
• [28]Tada T, Natsuaki M, Morimoto T, Furukawa Y, Nakagawa Y, Byrne RA, Kastrati A, Kadota K, Iwabuchi M, Shizuta S, Tazaki J, Shiomi H, Abe M, Ehara N, Mizoguchi T, Mitsuoka H, Inada T, Araki M, Kaburagi S, Taniguchi R, Eizawa H, Nakano A, Suwa S, Takizawa A, Nohara R, Fujiwara H, Mitsudo K, Nobuyoshi M, Kita T, Kimura T, et al.: Duration of dual antiplatelet therapy and long-term clinical outcome after coronary drug-eluting stent implantation: landmark analyses from the CREDO-Kyoto PCI/CABG Registry Cohort-2. Circ Cardiovasc Interv 2012, 5:381-391.
• [29]Eisenstein EL, Anstrom KJ, Kong DF, Shaw LK, Tuttle RH, Mark DB, Kramer JM, Harrington RA, Matchar DB, Kandzari DE, Peterson ED, Schulman KA, Califf RM: Clopidogrel use and long-term clinical outcomes after drug-eluting stent implantation. JAMA 2007, 297:159-168.
• [30]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.
• [31]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.
• [32]Mauri L, Kereiakes DJ, Normand SL, Wiviott SD, Cohen DJ, Holmes DR, Bangalore S, Cutlip DE, Pencina M, Massaro JM: Rationale and design of the dual antiplatelet therapy study, a prospective, multicenter, randomized, double-blind trial to assess the effectiveness and safety of 12 versus 30 months of dual antiplatelet therapy in subjects undergoing percutaneous coronary intervention with either drug-eluting stent or bare metal stent placement for the treatment of coronary artery lesions. Am Heart J 2010, 160:1035-1041.
• [33]Byrne RA, Schulz S, Mehilli J, Iijima R, Massberg S, Neumann FJ, ten Berg JM, Schomig A, Kastrati A: Rationale and design of a randomized, double-blind, placebo-controlled trial of 6 versus 12 months clopidogrel therapy after implantation of a drug-eluting stent: The Intracoronary Stenting and Antithrombotic Regimen: Safety And EFficacy of 6 Months Dual Antiplatelet Therapy After Drug-Eluting Stenting (ISAR-SAFE) study. Am Heart J 2009, 157:620-624.
• [34]Feres F, Costa RA, Abizaid A, Leon MB, Marin-Neto JA, Botelho RV, King SB III, Negoita M, Liu M, de Paula JE, Mangione JA, Meireles GX, Castello HJ Jr, Nicolela EL Jr, Perin MA, Devito FS, Labrunie A, Salvadori D Jr, Gusmão M, Staico R, Costa JR Jr, de Castro JP, Abizaid AS, Bhatt DL, OPTIMIZE Trial Investigators: Three vs twelve months of dual antiplatelet therapy after zotarolimus-eluting stents: the OPTIMIZE randomized trial. JAMA 2013, 310:2510-2522.
• [35]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.
• [36]Pandit A, Giri S, Hakim FA, Fortuin FD: Shorter (/=12 months) duration dual antiplatelet therapy after drug eluting stents: A meta-analysis of randomized clinical trials. Catheter Cardiovasc Interv 2014, 10. doi:10.1002/ccd.25520
• [37]Kim BK, Hong MK, Shin DH, Nam CM, Kim JS, Ko YG, Choi D, Kang TS, Park BE, Kang WC, Lee SH, Yoon JH, Hong BK, Kwon HM, Jang Y, RESET Investigators: A new strategy for discontinuation of dual antiplatelet therapy: the RESET Trial (REal Safety and Efficacy of 3-month dual antiplatelet Therapy following Endeavor zotarolimus-eluting stent implantation). J Am Coll Cardiol 2012, 60:1340-1348.
• [38]Valgimigli M, Campo G, Monti M, Vranckx P, Percoco G, Tumscitz C, Castriota F, Colombo F, Tebaldi M, Fuca G, Kubbajeh M, Cangiano E, Minarelli M, Scalone A, Cavazza C, Frangione A, Borghesi M, Marchesini J, Parrinello G, Ferrari R, Prolonging Dual Antiplatelet Treatment After Grading Stent-Induced Intimal Hyperplasia Study (PRODIGY) Investigators: Short- versus long-term duration of dual antiplatelet therapy after coronary stenting: a randomized multicentre trial. Circulation 2012, 125:2015-2026.
• [39]Gwon HC, Hahn JY, Park KW, Song YB, Chae IH, Lim DS, Han KR, Choi JH, Choi SH, Kang HJ, Koo BK, Ahn T, Yoon JH, Jeong MH, Hong TJ, Chung WY, Choi YJ, Hur SH, Kwon HM, Jeon DW, Kim BO, Park SH, Lee NH, Jeon HK, Jang Y, Kim HS: Six-month versus 12-month dual antiplatelet therapy after implantation of drug-eluting stents: the Efficacy of Xience/Promus Versus Cypher to Reduce Late Loss After Stenting (EXCELLENT) randomized, multicenter study. Circulation 2012, 125:505-513.
• [40]Park SJ, Park DW, Kim YH, Kang SJ, Lee SW, Lee CW, Han KH, Park SW, Yun SC, Lee SG, Rha SW, Seong IW, Jeong MH, Hur SH, Lee NH, Yoon J, Yang JY, Lee BK, Choi YJ, Chung WS, Lim DS, Cheong SS, Kim KS, Chae JK, Nah DY, Jeon DS, Seung KB, Jang JS, Park HS, Lee K: Duration of dual antiplatelet therapy after implantation of drug-eluting stents. N Engl J Med 2010, 362:1374-1382.
• [41]LaFleur J, Nelson RE, Sauer BC, Nebeker JR: Overestimation of the effects of adherence on outcomes: a case study in healthy user bias and hypertension. Heart 2011, 97:1862-1869.
• [42]Bangalore S, Kumar S, Fusaro M, Amoroso N, Attubato MJ, Feit F, Bhatt DL, Slater J: Short- and long-term outcomes with drug-eluting and bare-metal coronary stents: a mixed-treatment comparison analysis of 117 762 patient-years of follow-up from randomized trials. Circulation 2012, 125:2873-2891.