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Clopidogrel is more effective than ticlopidine for preventing minor myocardial injury after elective coronary stenting
TREATMENT
Clopidogrel is more effective than ticlopidine for preventing minor myocardial injury after elective coronary stenting Abstracted from: AtmacaY, Dandachi R, Gulec S et al. Comparison of clopidogrel versus ticlopidine for prevention of minor myocardial injury after elective coronary stenting. Int J Cardiol 2003; 87: 143^149.
BACKGROUND Recent studies suggest that even minor elevations in cardiac enzymes due to coronary interventions are associated with poor prognoses. Although there have been several studies examining ticlopidine versus clopidogrel on stent thrombosis rate, there are few data on the comparative e¡ectiveness of ticlopidine versus clopidogrel in reducing minor myocardial injury. OBJECTIVE To compare the e¡ectiveness of clopidogrel versus ticlopidine in reducing both minor myocardial injury and major clinical events in people who have undergone elective coronary stenting. SETTING Turkey; March 1998 toJanuary 2001. METHOD Randomized, double-blind study. PARTICIPANTS One hundred and ¢fty-eight consecutively enrolled patients with Canadian Cardiac Society Class-II stable angina pectoris and new lesions in large coronary arteries undergoing elective single vessel PTCAwith stenting. Exclusion criteria were unstable angina; acute myocardial infarction within 2 weeks;12lead resting electrocardiogram with right or left bundle branch block; paced rhythm or complete atrioventricular block; aorta^coronary by-pass operation within 2 weeks; renal dysfunction; pericardial disease; cardiomyopathy, and recent myocarditis. People were also excluded if they had received a stent as a bailout indication or if they had been given tiro¢ban during the procedure.
136
Evidence-based Cardiovascular Medicine (2003) 7,136 ^137 doi:10.1016/S1361-2611(03)00065- 4
INTERVENTION Clopidogrel (300 mg as a loading dose and 75 mg/day thereafter) versus ticlopidine (250 mg twice daily). Both thienopyridines were started on the same day as stent placement. Follow-up occurred during the hospital stay (672 days). MAIN OUTCOMES The primary outcome was procedure-related minor myocardial injury (assessed by cardiac troponinT [cTnT] levels 12 hours post-procedure). Secondary outcomes were major clinical events (death, acute myocardial infarction and repeat revascularization). MAIN RESULTS Signi¢cantly more people in the ticlopidine group exhibited abnormal cTnT levels 12 hours after stent implantation (po0.01). Abnormal cTnT levels were also signi¢cantly higher in the ticlopidine group than those of the clopidogrel group (0.4470.12 v 0.3870.11ng/mL, po0.001). There was no signi¢cant di¡erence in the rate of major clinical events between groups. AUTHORS’ CONCLUSIONS Combined clopidogrel and aspirin was more e¡ective in reducing the rate of minor myocardial injury after elective coronary stenting than combined ticlopidine and aspirin. Sources offunding: Not Speci¢ed. Correspondenceto: KK Mahallesi,11Cadde, Final Sitesi, 2-B Blok, No. 8 Batikent, Ankara,Turkey.Tel.: +90-312-256-9710; Email: [email protected] Abstract provided by Bazian Ltd, London.
1361-2611/03/$ - see front matter & 2003 Elsevier Ltd. Allrights reserved.
Commentary Acute antiplatelet therapy for patients undergoing coronary stenting had reduced significantly subacute thrombosis and myocardial injury and become a standard of care for patients undergoing percutaneous coronary intervention (PCI). Aspirin was not potent enough to prevent thrombotic events following stenting and the introduction of the thienopyridines, initially ticlopidine, followed by clopidogrel, further reduced thrombotic events. The comparison between ticlopidine and clopidogrel in this double-blinded trial enabled the investigators to detect differences in troponinTrelease in favor of clopidogrel, and a trend towards fewer events in the clopidogrel group. The trial results may not, however, solely reflect differences in the properties and mechanism of action of the drugs, which probably should have the same class effect. Rather, the findings of the present study might be explained by the time of the administration of the drug.The recent CREDO1 study found that clopidogrel given at least 6 hours prior to PCI reduced events compared with clopidogrel given within 6 hours. In the present study, the exact time of administration of clopidogrel prior to PCI is not given. Therefore, it is difficult to determine whether the events in patients who were on clopidogrel and aspirin were related to the time of the administration of the clopidogrel. We already know, however, that ticlopidine requires a higher loading dose and administration up to 3 days prior to the intervention to reach its full effect as an antiplatelet agent, suggesting that time of administration may have confounded treatment effects in the present study. With the recent data from PCI- CURE2 and the CREDO studies, there is a shift not only towards earlier pretreatment but also longer continuation of clopidogrel after PCI. The ACC/AHA guidelines3 recommend treatment duration of 9 months after PCI in patients with unstable angina or non-STsegment elevation myocardial infarction. The CREDO study demonstrated that 12 months of clopidogrel after PCI further reduced cardiac events.
Longer-term antiplatelet therapy brings with it a greater risk of adverse events. This consideration has put ticlopidine out of the running in favor of clopidogrel and aspirin. Given the clear and now well-known advantages of clopidogrel and aspirin over ticlopidine, and the possibility of confounding of the present study’s results by time of administration, it could be argued that the present results are now of theoretical interest. The focus of future studies should be to investigate optimum timing and duration of clopidogrel in patients undergoing intracoronary stenting, and to compare the effectiveness of clopidogrel with the glycoprotein IIb/IIIa inhibitors. Ron Waksman MD Division of Cardiology Washington Hospital Center Washington DC, USA
Literature cited 1. Steinhubl SR, Berger PB, Mann JT, 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. 2. Metha SR, Yusuf S, Peters RJ et al. for the CURE Trial 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 (9281): 527^533. 3. Braunwald E, Antman EM, Beasley JW et al. ACC/AHA 2002 guideline update for the management of patients with unstable angina and non-ST-segment elevation, myocardial infarction ^ Summary article. a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Committee on the Management of Patients with Unstable Angina). J Am Coll Cardiol 2002; 40: 1366 ^1374.
Evidence-based Cardiovascular Medicine (2003) 7,136^137
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Clopidogrel is more effective than ticlopidine for preventing minor myocardial injury after elective coronary stenting Abstracted from: AtmacaY, Dandachi R, Gulec S et al. Comparison of clopidogrel versus ticlopidine for prevention of minor myocardial injury after elective coronary stenting. Int J Cardiol 2003; 87: 143^149.
BACKGROUND Recent studies suggest that even minor elevations in cardiac enzymes due to coronary interventions are associated with poor prognoses. Although there have been several studies examining ticlopidine versus clopidogrel on stent thrombosis rate, there are few data on the comparative e¡ectiveness of ticlopidine versus clopidogrel in reducing minor myocardial injury. OBJECTIVE To compare the e¡ectiveness of clopidogrel versus ticlopidine in reducing both minor myocardial injury and major clinical events in people who have undergone elective coronary stenting. SETTING Turkey; March 1998 toJanuary 2001. METHOD Randomized, double-blind study. PARTICIPANTS One hundred and ¢fty-eight consecutively enrolled patients with Canadian Cardiac Society Class-II stable angina pectoris and new lesions in large coronary arteries undergoing elective single vessel PTCAwith stenting. Exclusion criteria were unstable angina; acute myocardial infarction within 2 weeks;12lead resting electrocardiogram with right or left bundle branch block; paced rhythm or complete atrioventricular block; aorta^coronary by-pass operation within 2 weeks; renal dysfunction; pericardial disease; cardiomyopathy, and recent myocarditis. People were also excluded if they had received a stent as a bailout indication or if they had been given tiro¢ban during the procedure.
136
Evidence-based Cardiovascular Medicine (2003) 7,136 ^137 doi:10.1016/S1361-2611(03)00065- 4
INTERVENTION Clopidogrel (300 mg as a loading dose and 75 mg/day thereafter) versus ticlopidine (250 mg twice daily). Both thienopyridines were started on the same day as stent placement. Follow-up occurred during the hospital stay (672 days). MAIN OUTCOMES The primary outcome was procedure-related minor myocardial injury (assessed by cardiac troponinT [cTnT] levels 12 hours post-procedure). Secondary outcomes were major clinical events (death, acute myocardial infarction and repeat revascularization). MAIN RESULTS Signi¢cantly more people in the ticlopidine group exhibited abnormal cTnT levels 12 hours after stent implantation (po0.01). Abnormal cTnT levels were also signi¢cantly higher in the ticlopidine group than those of the clopidogrel group (0.4470.12 v 0.3870.11ng/mL, po0.001). There was no signi¢cant di¡erence in the rate of major clinical events between groups. AUTHORS’ CONCLUSIONS Combined clopidogrel and aspirin was more e¡ective in reducing the rate of minor myocardial injury after elective coronary stenting than combined ticlopidine and aspirin. Sources offunding: Not Speci¢ed. Correspondenceto: KK Mahallesi,11Cadde, Final Sitesi, 2-B Blok, No. 8 Batikent, Ankara,Turkey.Tel.: +90-312-256-9710; Email: [email protected] Abstract provided by Bazian Ltd, London.
1361-2611/03/$ - see front matter & 2003 Elsevier Ltd. Allrights reserved.
Commentary Acute antiplatelet therapy for patients undergoing coronary stenting had reduced significantly subacute thrombosis and myocardial injury and become a standard of care for patients undergoing percutaneous coronary intervention (PCI). Aspirin was not potent enough to prevent thrombotic events following stenting and the introduction of the thienopyridines, initially ticlopidine, followed by clopidogrel, further reduced thrombotic events. The comparison between ticlopidine and clopidogrel in this double-blinded trial enabled the investigators to detect differences in troponinTrelease in favor of clopidogrel, and a trend towards fewer events in the clopidogrel group. The trial results may not, however, solely reflect differences in the properties and mechanism of action of the drugs, which probably should have the same class effect. Rather, the findings of the present study might be explained by the time of the administration of the drug.The recent CREDO1 study found that clopidogrel given at least 6 hours prior to PCI reduced events compared with clopidogrel given within 6 hours. In the present study, the exact time of administration of clopidogrel prior to PCI is not given. Therefore, it is difficult to determine whether the events in patients who were on clopidogrel and aspirin were related to the time of the administration of the clopidogrel. We already know, however, that ticlopidine requires a higher loading dose and administration up to 3 days prior to the intervention to reach its full effect as an antiplatelet agent, suggesting that time of administration may have confounded treatment effects in the present study. With the recent data from PCI- CURE2 and the CREDO studies, there is a shift not only towards earlier pretreatment but also longer continuation of clopidogrel after PCI. The ACC/AHA guidelines3 recommend treatment duration of 9 months after PCI in patients with unstable angina or non-STsegment elevation myocardial infarction. The CREDO study demonstrated that 12 months of clopidogrel after PCI further reduced cardiac events.
Longer-term antiplatelet therapy brings with it a greater risk of adverse events. This consideration has put ticlopidine out of the running in favor of clopidogrel and aspirin. Given the clear and now well-known advantages of clopidogrel and aspirin over ticlopidine, and the possibility of confounding of the present study’s results by time of administration, it could be argued that the present results are now of theoretical interest. The focus of future studies should be to investigate optimum timing and duration of clopidogrel in patients undergoing intracoronary stenting, and to compare the effectiveness of clopidogrel with the glycoprotein IIb/IIIa inhibitors. Ron Waksman MD Division of Cardiology Washington Hospital Center Washington DC, USA
Literature cited 1. Steinhubl SR, Berger PB, Mann JT, 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. 2. Metha SR, Yusuf S, Peters RJ et al. for the CURE Trial 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 (9281): 527^533. 3. Braunwald E, Antman EM, Beasley JW et al. ACC/AHA 2002 guideline update for the management of patients with unstable angina and non-ST-segment elevation, myocardial infarction ^ Summary article. a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Committee on the Management of Patients with Unstable Angina). J Am Coll Cardiol 2002; 40: 1366 ^1374.
Evidence-based Cardiovascular Medicine (2003) 7,136^137
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