Lack of efficacy of clopidogrel pretreatment in the prevention of myocardial damage after elective stent implantation - Lack of efficacy of clopidogrel pretreatment in the prevention of myocardial damage after elective stent implantation
The goal the study was to evaluate the effect of pretreatment with clopidogrel compared with standard postprocedural clopidogrel among patients undergoing elective stent implantation.
Patients Enrolled: 203
Mean Follow Up: Six months
Mean Patient Age: Mean age 61 years
Primary intervention for acute MI or other emergency procedures, elevated baseline troponin I or CK-MB levels, known intolerance of clopidogrel or aspirin, long-term use of nonsteroidal anti-inflammatory drugs, planned periprocedural treatment with GP IIb/IIIa inhibitors, or known thrombocytopenia
Rise in troponin I or CK-MB fraction serum levels at 6-8 and 16-24 hours after PCI
Death, stroke, MI, CABG, repeated PCI, and subacute stent thrombosis at one and six months after PCI
Patients were randomized to three days of pretreatment with clopidogrel (n=101) or standard postprocedure clopidogrel (n=102). The pretreatment group received 300 mg of clopidogrel three days before coronary stent implantation. In the no pretreatment group, a loading dose of 300 mg was given immediately postprocedure. All patients received 75 mg per day of clopidogrel for four weeks postprocedure.
Initial heparin bolus of 10,000 IU and 5000 U bolus given for every additional hour of the procedure, and aspirin 100 mg per day for at least six months
There was no difference by treatment group in troponin I elevation at 24 hours postprocedure (43.3% for nonpretreatment vs. 51.1% for pretreated patients; p=0.31). There was also no difference in troponin elevation at 6-8 hours (17.2% vs. 20.4%, p=0.70). A similar lack of benefit occurred with creatine kinase-MB (CK-MB) elevation at both 6-8 hours (3.3% for nonpretreatment vs. 3.2% for pretreatment, p=1.0) and 24 hours (6.3% vs. 7.4%, p=0.78).
Clinical events did not differ at one month or six months. At one month, there was no subacute stent thrombosis, death, or stroke. At six months, repeat percutaneous coronary intervention (PCI) was performed in 5% of patients in the nonpretreatment group compared with 8% in the pretreatment group (p=0.57), and coronary artery bypass graft (CABG) in 1% and 2% (p=1.0), respectively. There was one death in each group (p=1.0). Myocardial infarction (MI) occurred in 3% in the nonpretreatment group and none in the pretreatment group (p=0.12). The overall composite event rate was 12% and 13% (p=0.82), respectively.
Among patients undergoing elective coronary stent implantation, pretreatment with clopidogrel was not associated with a difference in postprocedure troponin or CK-MB elevation or in clinical events compared with immediate postprocedure clopidogrel administration.
These data differ from the recent CREDO trial, which showed no difference between clopidogrel and placebo in the overall study, but did show a reduction in events associated with clopidogrel in the subgroup of patients pretreated for >6 hours prior to PCI. Although there have been several nonrandomized or subgroup studies, the present study is one of the first randomized trials to evaluate pre-PCI versus post-PCI initiation of clopidogrel. The advantage of post-PCI initiation of clopidogrel is that the anatomy can be defined before administering clopidgrel, which is beneficial in patients who must undergo CABG due to the potential increase in bleeding.
On the contrary, pretreatment with clopidogrel may provide earlier blockage of platelet aggregation, resulting in prevention of periprocedural thrombus formation. As the authors note, the data from the present trial do not support the latter hypothesis, but it is important to note that this may be due to the population studied (elective stenting in patients with stable angina) and may not apply to patients with acute coronary syndromes.
Van Der Heijden DJ, Westendorp IC, Riezebos RK, et al. Lack of efficacy of clopidogrel pre-treatment in the prevention of myocardial damage after elective stent implantation. J Am Coll Cardiol 2004;44:20-4.
Keywords: Myocardial Infarction, Stroke, Acute Coronary Syndrome, Creatine Kinase, Follow-Up Studies, Platelet Aggregation Inhibitors, Angina, Stable, Ticlopidine, Purinergic P2Y Receptor Antagonists, Percutaneous Coronary Intervention, Stents, Thrombosis, Troponin I, Coronary Artery Bypass
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