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1 w wz 15«2y Kor. J. Clin. Pharm., Vol. 15, No lp z$mpqjephsfm $JMPTUB[PM E BCÁ»CDÁ B w w w C s w D s w w E w w w w Comparison of Clopidogrel versus Cilostazol in Coronary Artery Stenting In Sook Song a,b, Seung Ki Choi b,c and Jung Mi Oh d a Graduate School of Clinical Pharmacy, Sookmyung Women s University, Seoul, 14742, Korea b Dept of Pharmacy, Bundang CHA General Hospital c Department of Pharmacology, College of Medicine, Pochon CHA University, Sungnam, Kyonggido, , Korea d College of Pharmacy, Seoul national University, Seoul, , Korea Following intracoronary stenting, antiplatelet therapy lead to greater protection from thrombotic complication. A few data are available about the effect of clopidogrel versus cilostazol, an antiplatelet commonly used after intracoronary stenting. To evaluate the efficacy and safety of clopidogrel plus aspirin compared with those of cilostazol plus aspirin in coronary stenting and to evaluate the efficacy of clopidogrel loading dose prior to coronary stenting in clopidogrel group. Data were retrospectively collected from medical charts of patients who had undergone coronary stenting and received either clopidogrel with or without loading 3 mg followed by 75 mg/d (n=58), or 2 mg/d cilostazol (n=72) for 1 year, between January 2 and May 22. All patients in both groups received aspirin 2 mg/d throughout the study. The primary endpoints at 7, 3, 18 and 365 days after stenting were the composite of death, Myocardial Infarction, stroke, angina, and revascularization in the intent to treat population and restenosis at follow up angiography. The secondary endpoints were the incidence of bleeding complications at 7, 3, and 365 days, and durg adverse effects at 365 days after stenting. At 18 and 365 days after stenting, the combined primary endpoints were significantly reduced in clopidogrel plus aspirin group (relative risk.39; 95% CI.17 to.92; p=.21, RR.43; 95% CI.22 to.84; p=.85, respectively). However, the combined primary endpoints were not significantly different between the two groups at 7 and 3 days (p=1., p=.79, respectively). Angiographic restenosis rate was 14.3% in clopidogrel plus aspirin group and 32.1% in cilostazol plus aspirin group (p=.19). 3 mg of clopidogrel loading dose did not significantly reduce the combined primary endpoints at 3 days after stenting (RR.14; 95% CI.1 to 2.65; p=.23). The rate of bleeding complications and drug adverse effects were not different between the two groups. In patients undergoing intracoronary stenting, clopidogrel plus aspirin therapy is more beneficial than cilostazol plus aspirin in reducing major adverse cardiac events with similar rate of bleeding complication. A loading dose of clopidogrel did not lead to a statistically significant reduction in major adverse cardiac events. Key words clopidogrel, cilostazol, intracoronary stenting, major adverse cardiac events, bleeding complication y y w x ù x œ x ù, w w. y l ƒ w š ù Correspondence to : ƒ y wì y ƒw 1). w x e t y w l p œ š x j š z lp w x y jš x k w w lp ƒ š 2,3). w lp ƒ lp z w w lp x 4) z x ù,, z xx w š 5). 1

2 2 Kor. J. Clin. Pharm., Vol. 15, No. 2, 25 lp z x ( xx w ) w» w heparin, w š, aspirin w n w w š w ù x w 6), wx q w x w jš» g. l 7) p z w wx q t aspirin thienopyridine ticlopidine w ticlopidine x š wx q z ùkü 25 8), aspirin w š w x x x w k š šw. ù 9) ticlopidine û e ùkú, x q,» ƒ š 1), w v w. Cilostazol x q camp phosphodiesterase type III k w x q x y w» ƒ lp z» ticlopidine w z e š 11). Park ù 12) Yoon w 13) cilostazol ticlopidine ƒ wx q ƒ, Kozuma ù 14) Kamishirado w ticlopidine w 15) x jš, ƒw w š šw 1215). Clopidogrel thienopyridine k š ƒ platelet adenosine diphosphate(adp) receptor inhibitor x q ey platelet fibrinogen receptor(gpiib/iiia) y w aspirin n w wx q z ƒ š 16). w ticlopidine w wx q z ùküš 17), x e w 18). CLASSICS 5) clopidogrel ticlopidine w wš ƒ w wx q z w š šw. Clopidogrel 3 mg w (loading dose) n w n w š 75 mg n w x š 5 µmol/l ADPinduced platelet aggregation g x w»z ƒ 19). PCICURE 2), CREDO lp 21) clopidogrel 3 mg w ew z» n w (major adverse cardiac events, MACE),,, x jš x w ƒ š šw.» w clopidogrel cilostazol lp z wx q ticlopidine w z š š, Lee 32) w lp z 3 cilostazol clopidogrel j wš z wx q š šw. lp y lp clopidogrelaspirin w ù cilostazolaspirin w» n w y wx z w w z sƒwš clopidogrelaspirin ü lp e 3 mg w n w e w sƒwš w s w 2 1 l 22 5 ¾ lp w y y,» w zw w w. sw» lp w y clopidogrelaspirin n y ù cilostazolaspirin n y 1 ƒ w y w.» (left main coronary artery) x y, 3 qw y, aspirin, clopidogrel, cilostazol wx q ƒ w y w. x x q (<15,/ mm 3 ) y ù w y (serum creatinine> 2 mg/dl), lp 24 x w w y, lp z w š w y, lp(drugeluting stent) y w. lp y clopidogrelaspirin w y ù cilostazolaspirin w y» p w» w,» w w w., y» p w» w y,,,» wš x sƒw» w x w hemoglobin(hgb), hematocrit (Hct), platelet(plt) lp ww» w z 24, 48, n e w., y x šx, š x,,,, ƒ, x ù, x» y w., aspirin, βblocker, w (lipid lowering agents), ACE inhibitor, calcium channel blocker, nitrates, heparin xy w.,» (coronary angiographic

3 lp z Clopidogrel Cilostazol 3 report)ù v x (Percutaneous Transluminal Coronary Angioplasty, w PTCA)» w l p x ü, x ü, x x, x e[left anterior discending(lad), left circumflex(lcx), right coronary artery(rca)] wš lp w (urgent) k(elective) w š lp x (target vessel), lp ¼, x (residual stenosis) w., lp (Qwave, Non Qwave), x x, x x w w., lp z x sƒw» w 6 ù z ww» mw w., x e w q wš glycoprotein b/a receptor antagonist( w GpIIb/IIIa receptor antagonist) w. wx q n Clopidogrel 3 mg w n w ù w n l 75 mg 1 1z n w š cilostazol 1 mg 1 2z n w aspirin 2 mg 1 1z n w. ƒƒ lp l 1 n. &OEQPJOUsƒ ƒ x sƒw. Primary endpoint» w (MACE) lp x sƒw. Clopidogrelaspirin e clopidogrel w n w w n, sƒw. l p z 7, 3, 6, 12 w w., x, (Qwave non Qwave),, x (revascularization) w. w x w. x» chest pain(+), angina(+)» w š, creatine kinase( w CK) ƒ we 2 ƒw CKMB ƒ ƒw w š, x ù w w. x lp z 3 z ww t x (urgent target revascularization), 3 z ww t x (any target revascularization), t x x ww»kx (any revascularization) š w. lp x lp wš 6 ù z ww y lp w ü 5% w. Secondary endpoint x w sƒw. x w lp z 7, 3, 12 w w w š lp z 12 w w. x major bleeding minor bleeding w w 5). Major bleeding ü x(intracranial bleeding), ü x, y x, x w x, x q (<1,/mm 3 ), n (access site) x, hemoglobin eƒ baseline w 3g/dl ƒ w. Minor bleeding major bleeding x( ü x, x, x ) w. w Endpoint w e w» w x, šx, š x, w, βblocker, ACE inhibitor, calcium channel blocker, heparin, GpII b/iiia receptor antagonist multivariate analysis w. m intentiontotreat e w t ttest, x relative risk 95% confidence intervals(cis) ùkü š Chisquare test Fisherexact test w. Timetoevent curve KaplanMeier estimator w ƒ logrank test w. Endpoint w e w» w multivariate analysis stepwise w logistic regression w. SAS 8.2 version w p<.5 m w š w. y p y lp y ƒ w y 13 clopidogrelaspirin 58, cilostazolaspirin 72. Clopidogrelaspirin cilostazolaspirin s³ (59±1.6, 6±9.5 ), (û / : 39 /19, 45 /27 ), (68.3±11.4 kg, 65.5±1.7 kg), Hgb(13.7± 1.5 g/dl, 13.5±1.5 g/dl), Hct(4.2±4.7%, 4.4±4.3%), PLT(249.4 ± mm, 265.8± mm)» p w. lp w clopidogrelaspirin 19 (32.7%),

4 4 Kor. J. Clin. Pharm., Vol. 15, No. 2, 25 Table 1. Baseline demographics Factor Clopidogrel (n=58) Cilostazol (n=72) p value Age, mean (±SD), y Men, no.(%) Weight, mean (±SD), kg Height, mean (±SD), cm 59 (±1.6) 39 (67.2) 68.3 (±11.4) (±8.5) 6 (±9.5) 45 (62.5) 65.5 (±1.7) 161. (±8.7) Risk factor, no.(%) Previous angina Previous myocardial infarction Stroke Diabetes melitus Hypertension Hyperlipidemia Congestive heart failure Smoking Family history of heart disease Concomitant drugs, no.(%) Aspirin βblocker Lipid lowering agent ACE * inhibitor Calcium channel blocker Nitrates Heparin No. of diseased vessel, no.(%) Left anterior descending Left circumflex Right coronary artery Reference diameter, mean (±SD), mm Procedure MLD, mean (±SD), mm Procedure diameter stenosis, mean (±SD),% Hemoglobin, mean (±SD), g/dl Hematocrit, mean (±SD), % Platelet, mean (±SD), x1 3 /mm 3 36 (62.1) 6 (1.3) 8 (13.8) 17 (29.3) 36 (62.1) 21 (36.2) 6 (1.3) 22 (37.9) 5 (8.6) 58 (1) 47 (81.) 32 (55.2) 38 (65.5) 27 (46.6) 27 (46.6) 38 (65.5) 33 (56.9) 17 (29.3) 8 (13.8) 38 (65.5) 18 (31.6) 35 (6.3) 3.25 (±.47).86 (±.49) (±14.11) 13.7 (±1.5) 4.2 (±4.7) (±7.1) 33 (45.8) 6 (8.3) 24 (33.3) 39 (54.2) 16 (22.2) 6 ( (47.2) 72 (1) 61 (84.7) 44 (62.) 59 (83.1) 46 (64.8) 25 (35.2) 57 (79.2) 39 (54.2) 23 (31.9) 1 (13.9) 51 (7.8) 29 (4.3) 35 (48.6) 3.37 (±.48).79 (±.39) 76.6 (±11.16) 13.5 (±1.5) 4.4 (±4.3) (±69.2) Length of stay, mean (±SD), days 5. (±2.8) 5.2 (±2.7).6 * ACE=angiotensin convert enzyme, MLD=minimal luminal diameter x x 35 (6.3%), x x 4 (6.9%) š, cilostazolaspirin 26 (36.1%), x x 44 (61.1%), x x 2 (2.8%) ƒ. y p Table 1. x clopidogrelaspirin 8 (13%) clopidogrelaspirin w (p<.12). x ƒ (Table 1). Clopidogrelaspirin cilostazolaspirin lp z ACE inhibitor ƒƒ 38 (65.5%), 59 (83.1%) [p=.2], calcium channel blocker ƒƒ 27 (46.6%), 46 (64.8%) [p=.3] cilostazolaspirin w w, lp z heparin n w cilostazolaspirin w ùkû (p=.8)(table 1). p lp x ü, x ü, x, x s, x w (Table 1). lp p w lp, lp ¼, lp ƒ š lp w t x LADù RCA ƒ LCx cilostazolaspirin w (p=.3)(table 2).

5 lp z Clopidogrel Cilostazol 5 Table 2. Procedural characteristics Clopidogrel (n=58) Cilostazol (n=72) p value Successful stent, no.(%) (<2% residual stenosis) 58 (1) 58 (1) Received stent, no.(%) (91.4) 5 (8.6) 61 (84.7) 11 (15.3) No. of stents per patient, mean (±SD) 1.1 (±.3) 1.2 (±.4).25 Stent length per patient, mean(±sd), mm 19. (±5.2) 17.5 (±4.9).12 Indication for stenting, no.(%) Acute myocardial infarction NonQ wave Q wave Unstable angina Stable angina Time of procedure, no.(%) Elective Urgent Vessel of target lesion, no.(%) Left anterior descending Left circumflex Right coronary artery 5 (8.6) 14 (24.1) 35 (6.3) 5 (86.2) 8 (13.8) 31 (53.5) 6 (1.3) 25 (43.1) 8 (11.1) 18 (25.) 44 (61.1) 59 (81.9) 13 (18.1) 37 (51.4) 18 (25.) 27 (37.5) Dose of heparin during procedure, mean (±SD), IU 8538 (±214) 7867 (±238).8 Gp * IIb/IIIa antagonist use, no.(%) 12 (2.7) 14 (19.7).89 *Gp=glycoprotein SJNBSZFOEQPJOU lp z Table 3. lp z 7 clopidogrelaspirin 1 (1.7%), cilostazolaspirin 1 (1.4%) w ƒ (p=1.). v w ù cilostazolaspirin lp z 1 (1.4%) 4 w. lp z 3 clopidogrelaspirin 3 (5.2%), cilostazolaspirin 3 (4.2%) w ƒ š(p=.79), x w clopidogrelaspirin 1 (1.7%), cilostazolaspirin 2 (2.8%) ƒ (p=.69). x clopidogrelaspirin 2 (3.5%), cilostazolaspirin 1 (1.4%) w ƒ š(p=.44), v w ù cilostazolaspirin 1 15 w. lp z 6 clopidogrelaspirin 6 (1.3%), cilostazolaspirin 19 (26.4%) cilostazolaspirin w (p=.21), x w w ƒ (p=.29). x clopidogrelaspirin 4 (6.9%), cilostazolaspirin 16 (22.2%) cilostazolaspirin w (p=.16), cilostazolaspirin 5 1 w ù w. 9 clopidogrelaspirin 3 (5.2%), cilostazolaspirin 6 (8.3%) w ùkü (p=.73), t x w š t x clopidogrelaspirin cilostazolaspirin ƒƒ 2 (3.5%), 3 (4.2%),»kx ƒƒ 1 (1.7%), 3 (4.2%) ƒƒ w w ùkü. lp z 12 clopidogrelaspirin 9 (15.5%), cilostazolaspirin 26 (36.2%) cilostazolaspirin w (p=.85), x w x cilostazolaspirin w (p=.36, p=.21)(table 3, Figures 1, 2). ù,, x w ƒ. lp x» lp z s³ 7 clopidogrelaspirin 21 (36.2%), cilostazolaspirin 28(38.8%) w. l p w ü 5% clopidogrelaspirin 3 (14.3%), cilostazolaspirin 9 (32.1%) ùkû ù w (p=.19)(table 6).

6 6 Kor. J. Clin. Pharm., Vol. 15, No. 2, 25 Table 3. Primary endpoint End point Clopidogrel (n=58) Cilostazol (n=72) Relative risk (95% CI ) p value From stent to 7 days n(%) n(%) Angina, MI *, stroke, death, revascularization 1 (1.7) 1.24 ( ) 1. MI, stroke, death, revascularization 1 (1.7) 1.24 ( ) 1. Angina Myocardial infarction 1 (1.7) 1.24 ( ) 1. Stroke.41 (.29.94) From stent to 3 days n(%) n(%) Angina, MI *, stroke, death, revascularization 3 (5.2) 1.24 ( ).79 MI, stroke, death, revascularization 1 (1.7).62 (.66.68).69 Angina 2.48 ( ).44 Myocardial infarction 1 (1.7) 1.24 ( ) 1. Stroke.41 (.29.94) (.29.94) Angina, MI *, stroke, death, revascularization 6 (1.3) 19 (26.4).39 (.17.92).21 MI, stroke, death, revascularization 9 (12.5).55 (.181.7).29 Angina 16 (22.2).31 (.11.88).16 Myocardial infarction 1 (1.7) 1.24 ( ) 1. Stroke.25 (.15.6).5 3 (5.2) 1 (1.7) 6 (8.3).62 ( ).83 ( ).41 (.43.88).41 (.29.94) From stent to 12 months n(%) n(%) Angina, MI *, stroke, death, revascularization 9 (15.5) 26 (36.2).43 (.22.84).85 MI, stroke, death, revascularization 5 (8.6) 16 (22.2).38 (.15.99).36 Angina 6 (1.3) 19 (26.4).39 (.17.92).21 Myocardial infarction 1(1.7).41 (.43.88).63 Stroke.25 (.15.6).5 * MI=myocardiac infarction TVR=target vessel revascularization CI=confidence interval 3 (5.2) 1 (1.7) 13 (18.1) 7(9.7) 6 (8.3).38 ( ).53 ( ).21 (.31.67).41 (.29.94)

7 lp z Clopidogrel Cilostazol 7 z 12 3 mg w n 75 mg w n ùkû [2(6.9%) vs 7(24.1%), RR.29(.61.26)](Table 5). Fig. 1. KaplanMeier cumulative hazard rates for angina, myocardial infarction, stroke, death, or revascularization. Fig. 2. KaplanMeier cumulative hazard rates for myocardial infarction, stroke, death, or revascularization. $MPQJEPHSFM w e FOEQPJOU Clopidogrelaspirin 3 mg w n w y 29 (5%) š w 75 mg n w y 9 (5%). sƒ w w ù lp z mg w n 1 w š 6 3 mg w n 75 mg w n ùkû [1(3.5%) vs 5(17.2%), RR.2(.31.61)]. x w w n y ùkû [1(3.5%) vs 3(1.3%), RR.33(.4 3.2)]. w lp 4FDPOEBSZFOEQPJOU Major bleeding w ƒ š [9 (15.5%) vs 1 (13.9%), p=.79] ü x ù x, x q. x w lp z 7 w y x clopidogrelaspirin 18 1 w. Minor bleeding w ƒ (p=.75), x 2 ùkûš x clopidogrelaspirin 2, x cilostazolaspirin 2 ùkû. x w. Gpb/a receptor antagonist n w y ù n w y x w w (Table 7). n» w w š clopidogrelaspirin m 1, xz 1 ùkûš cilostazolaspirin y» ƒ 3, m 3, 3, xz 3 ùkû (Table 4). w Multivariate analysis endpoint w e. š y e lp š ù lp z w lp x ù x w» w wx q n w w. 21 American College of Chest Physicians VI e 23) w lp z wx aspirin 8325 mg/day ticlopidine w 5 mg n z 25 mg 1 2z 114 n w ù clopidogrel w 3 mg n z 75 mg n w wš. lp heparin n wš š x GpIIb/IIIa receptor antagonist n wš ticlopidine w ticlopidine w ùk ú x w, x q, l w «šwš. w ticlopidine w w š clopidogrel cilostazol š 5,1215). Clopidogrel cilostazol» wx q t ticlopidine w w ƒ t. Ticlopidine cilostazol w Park 12), Yoon 13), Kozuma

8 8 Kor. J. Clin. Pharm., Vol. 15, No. 2, 25 Table 4. Secondary endpoint Clopidogrel (n=58) Cilostazol (n=72) Relative risk (95% CI ) p value From stent to 7 days n(%) n(%) Bleeding complication Major bleeding Intracranial Intraocular GI * bleeding Access site Decreased hemoglobin Thrombocytopenia Blood transfusion Minor bleeding Hematoma Hematuria Oral From stent to 3 days Bleeding complication Major bleeding Intracranial Intraocular GI * bleeding Access site Decreased hemoglobin Thrombocytopenia Blood transfusion Minor bleeding Hematoma Hematuria Oral From stent to 12 months Bleeding complication Major bleeding Intracranial Intraocular GI * bleeding Access site Decreased hemoglobin Thrombocytopenia Blood transfusion Minor bleeding Hematoma Hematuria Oral Other side effects Skin disorder GI * disturbance Headache Palpitation Dizziness * GI=gastrointestinal CI=confidence interval 8 (13.8) 3 (5.2) 5 (8.6) 3 (5.2) 9 (15.5) 1 (1.7) 3 (5.2) 6 (1.3) 9 (15.5) 1 (1.7) 3 (5.2) 6 (1.3) 1 (1.7) 1 (1.7) 1 (13.9) 7 (9.7) 1 (13.9) 7 (9.7) 4 (5.6) 1 (13.9) 7 (9.7) 4 (5.6).99 ( ) 3.72 (.434.9).89 (.32.65) 1.21 ( ) 1.66 (.397.1) 1.24 ( ).41 (.29.94) 6.19( ) 1.11 ( ) 3.72 ( ) 3.72 ( ) 1.6 ( ) 1.66 (.397.1) 1.24 ( ) 1.24 ( ).25 (.15.6) 6.19( ) 1.11 ( ) 3.72 ( ) 3.72 ( ) 1.6 ( ) 1.66 (.397.1) 1.24 ( ) 1.24 ( ).25 (.15.6) 6.19( ).18 (.13.35).41 (.43.87).18 (.13.35).41 (.43.87) ), Kamishirado 15) š ticlopidine clopidogrel w CLASSICS 5), Pache 22) ƒ. w cilostazol clopidogrel ƒ ticlopidine w z š š. Lee 32) w lp z cilostazol clopidogrel ƒƒ 3 n w y 3 w cilostazol clopidogrel j wš z š

9 lp z Clopidogrel Cilostazol 9 Table 5. Comparison of outcomes in clopidogrel group with or without LD 3 mg prior to coronary artery stenting LD 3 mg (n=29) 75 mg (n=29) Relative risk (95% CI ) p value From stent to 7 days n (%) n (%) Angina, MI *, stroke, death, revascularization 1 (3.5).33 (.17.86) 1. MI *, stroke, death, revascularization 1 (3.5).33 (.17.86) 1. Angina Myocardial infarction 1 (3.5).33 (.17.86) 1. Stroke From stent to 3 days n (%) n (%) Angina, MI *, stroke, death, revascularization 3 (1.3).14 (.12.65).23 MI *, stroke, death, revascularization 1 (3.5).33 (.17.86) 1. Angina 2 (6.9).2 (.13.79).49 Myocardial infarction 1 (3.5).33 (.17.86) 1. Stroke From stent to 6 months n (%) n (%) Angina, MI *, stroke, death, revascularization 1 (3.5) 5 (17.2).2 (.31.61).19 MI, stroke, death, revascularization 1 (3.5) 3 (1.3).33 (.43.2).61 Angina 1 (3.5) 3 (1.3).33 (.43.2).61 Myocardial infarction 1 (3.5).33 (.17.86) 1. Stroke 1 (3.5) 1 (3.5) 2 (6.9) 1 (3.5) 1 (3.5).5 (.55.21) 1. ( ).33 (.17.86) From stent to 12 months n (%) n (%) Angina, MI *, stroke, death, revascularization 2 (6.9) 7 (24.1).29 (.61.26).698 MI,stroke, death, revascularization 2 (6.9) 3 (1.3).67 (.123.7).64 Angina 1 (3.5) 5 (17.2).2 (.31.61).19 Myocardial infarction 1 (3.5).33 (.17.86) 1. Stroke * MI=myocardiac infarction TVR=target vessel revascularization CI=confidence interval 2 (6.9) 2 (6.9) 2 (6.9) 1 (3.5) 1 (3.5) 1. ( ) 2. ( ).33 (.17.86)

10 1 Kor. J. Clin. Pharm., Vol. 15, No. 2, 25 Table 6. Instent restenosis during the followup Clopidogrel (n=21) Cilostazol (n=28) p value CAG *, mean (±SD), months 7.5 (±2.1) 7.3 (±2.).64 Instent restenosis(isr) 5%>, no.(%) 3 (14.3) 9 (32.1).19 * CAG=coronary angiography Table 7. Bleeding at 3day for patients treated with GpIIb/ IIIa antagonist Gp * IIb/IIIa antagonist use, n(%) Yes No p value Clopidogrel (n=58) major 5 (8.6).73 minor 1. Cilostazol (n=72) major 7 (9.7).33 minor.62 * Gp=glycoprotein šw. ticlopidine z ƒ cilostazol clopidogrel lp l 1 n w y wx q z w ƒ. ƒ cilostazolaspirin 3 2.8% š Yoon 13) 1.4% ùkûš, 6 t x 4.2% š Kamishirado 15) 7% ùkû. Clopidogrelaspirin % š CLASSICS % 5) ùkû. Lee 32) w cilostazolaspirin clopidogreaspirin 3 lp x ƒƒ 2.6%, 2.% w š šw. clopidogrelaspirin cilostazolaspirin 3 w š 6 12 x,,, x m w w ù w (p=.2, p=.85)ƒ. lp z w w x ù x z ƒ w š. w lp z 36 w x ü sy s w ü x (late restenosis late stent occlusion) wš, w 24) w» w clopidogrelaspirin z š. w clopidogrelaspirin» n PCICURE ù 2) CREDO 21) w ùkû. w, x y w š y q x ƒ g z w w w š š, w y Creactive protein e ƒ š w. 26) Clopidogrelaspirin w Creactive protein e jš, 27) adenosine diphosphate w ù fibrinogen GpIIb/IIIa receptor antagonist w w w clopidogrel w wx q z, cilostazol x y ù x q w» w clopidogrel w w w. lp x ticlopidine w Song 6 z l 7) p x cilostazolaspirin 2.8% š, 9 (32.1%) ùkù clopidogrelaspirin 3 (14.3%) ùkù w ww y ƒ m w w clopidogrelaspirin x û ùkù ƒ š. wr, ü x š x ù ü x x ƒ {m ö x x y w š w. š w 28) primary endpoint x s ƒw w ƒ š. clopidogrelaspirin clopidogrel 3 mg w e w 3 CREDO w n w n 21) w ƒ. ù PCICURE 2) clopidogrel 3 mg w e n w n w w û w š šwš, CREDO subgroup y 21), z (acute coronary syndrome)y š šw. y ƒ subgroup w w w n 3 3 w ù w e n 1 w. m w w clopidogrel w n 2 wx q š z ùkü, w 19) lp w x clopidogrel w n ƒ z š. w, 12

11 lp z Clopidogrel Cilostazol 11 (p=.698) w 3 mg w e n ƒ w x w e š ƒ w w e n ƒ» e z e w š. x w» w w ƒ š x w cilostazolaspirin 13.9%, Yoon 13).7% š, clopidogrelaspirin 15.5% š, CREDO 4.8% ƒ 21). Yoon x 13) ƒ š, CREDO x 21) hemoglobin eƒ baseline w 5 g/dl ƒ y w 3 g/dl ƒ y sw gš lp óù z heparin n w» š. cilostazolaspirin ù w n w. Clopidogrel y» 1 m 1, 1 ùkû. Cilostazol 1 12 mg n w x y ƒ 57 beats/min ƒw» w 14) ùkù y ƒ 3 š m, y», ƒ ƒ 3 ùkû. y ƒ w ACE inhibitor cilostazolaspirin ùkû clopidogrelaspirin û. cilostazol clopidogrel ù w ƒ v w š. w w ù cilostazol» y jš š g l k š ƒ x 28) y w ƒ ù w w. lp z wx q w wì GpIIb/IIIa receptor antagonist w w š š, CREDO 21) GpIIb/IIIa receptor antagonistƒ x q w z GpIIb/IIIa receptor antagonist n ƒ n w y x w š šw. GpIIb/IIIa receptor antagonist tirofiban n w x w tirofiban n n w. EPISTENT ù 3) TARGET 31) w GpIIb/IIIa receptor antagonist n n x w g š šw ù y ƒ e w w w. Endpoint w e w» multivariate analysis w ù w w e. w Kim 25) šx x šw lp ww y šx ù y w y y ƒ v w š. w, zw» mw sƒw y ƒ w tw» y ƒ š ƒ, lp x w d z ü x zw w ƒ w w w. lp z x ù x w» w wx q kw œw j ƒ š ƒ z e w wz y sw g w ƒ v w. y e lp z 3 ü clopidogrelaspirin w cilostazolaspirin w w» (6, 12 ) clopidogrelaspirin w cilostazolaspirin w g. lp x clopidogrel 3 mg w e n w n w ƒ š x sww w ƒ. š x 1. y :, w y»wz, (23.3.3). 2. Serruys PW, de Jaegere P, Kiemeneij F, et al. A comparison of ballonexpandable stent implantaion with balloon angioplasty in patients with coronary artery disease. N Engl J Med 1994; 331: Fischman DL, Leon MB, Baim DS, et al. A randomized comparison of coronarystent placement and balloon angioplasty in treatment of coronary artery disease. N Engl J Med 1994; 331: Shaknovich A. Complications of coronary stenting. Coron Artery Dis 1994; 5:

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