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Clopidogrel as Adjunctive Reperfusion Therapy: Percutaneous Coronary Intervention Subgroup Study - PCI CLARITY
Description:
The goal of the study was to evaluate pretreatment with clopidogrel compared with placebo among the subgroup of patients with ST elevation myocardial infarction (STEMI) treated with thrombolytic therapy who underwent percutaneous coronary intervention (PCI) in the CLARITY-TIMI 28 trial.
Study Design
Study Design:
Patients Screened: 3,491
Patients Enrolled: 1,863
Mean Follow Up: 30 days
Mean Patient Age: Mean age 57 years
Female: 18
Patient Populations:
Age 18-75 years; ischemic discomfort within 12 hours and lasting at least 20 minutes; ST-segment elevation of ≥0.1 mV in ≥2 contiguous leads or new left bundle branch block; and scheduled to receive a fibrinolytic agent, an anticoagulant, and aspirin
Exclusions:
Treatment with clopidogrel in prior seven days or planned treatment with clopidogrel or a glycoprotein IIb/IIIa inhibitor before angiography; contraindications to fibrinolytic therapy; plan to perform angiography within 48 hours in the absence of a new clinical indication; cardiogenic shock; prior coronary artery bypass grafting; and a weight of ≤67 kg and receipt of more than a 4000 U bolus of unfractionated heparin, a weight of ≥67 kg and receipt of more than a 5000 U bolus of unfractionated heparin, or receipt of more than a standard dose of low molecular weight heparin
Drug/Procedures Used:
Patients in the CLARITY-TIMI 28 trial were randomized to treatment with clopidogrel (300 mg loading dose followed by 75 mg per day) or placebo following fibrinolytic therapy and aspirin. Patients were to undergo angiography 2-8 days after study drug initiation. PCI was performed at the discretion of the investigator.
Principal Findings:
Among the 3,491 patients in the overall trial, 1,863 patients (53.4%) underwent PCI during the index hospitalization at a median of three days post-randomization, with no difference in frequency of PCI by randomization group. Baseline characteristics were well-balanced between treatment groups. Pre-PCI patency was higher in the clopidogrel group (86.9% vs. 80.8%, p<0.001), but there was no difference in post-PCI patency (98.7% vs. 98.8%, p=NS). Open-label thienopyridine loading dose was given at the time of PCI in 77.6% of patients, and 90% received an open-label thienopyridine maintenance dose. Stents were used in 95% of cases.
The occurrence of reinfarction or stroke occurred less frequently in the clopidogrel group (4.0% vs. 6.2%, p=0.03). Likewise, the composite of cardiovascular death, reinfarction, or stroke following PCI was lower in the clopidogrel group compared with the placebo group (3.6% vs. 6.2%, p=0.008), as was cardiovascular death or MI (3.3% vs. 5.4%, p=0.03). Overall during the study, the rate of cardiovascular death, MI, or stroke pre- or post-PCI was lower in the clopidogrel group (7.5% vs. 12.0%, p=0.001). Results were similar across the various subgroups evaluated. There was no difference in the occurrence of TIMI major or minor bleeding by treatment group (2.0% vs. 1.9%, p=NS).
Interpretation:
Among STEMI patients treated with fibrinolytic therapy and aspirin who underwent PCI a median of three days later, pretreatment with clopidogrel was associated with a reduction in the composite of cardiovascular death, reinfarction, or stroke compared with no pretreatment in the CLARITY-TIMI 28 trial.
Clopidogrel, a prodrug, does not act immediately, but must first be metabolized in the liver by the cytochrome P450 pathway to reach its active form. Use of a loading dose decreases the time to reach platelet inhibition, but still takes several hours to fully activate. This CLARITY substudy of patients treated with PCI at the investigators' discretion demonstrated the importance of pretreatment with clopidogrel, as benefit was seen in the pretreatment group despite use of a loading dose in 78% of the no pretreatment group.
These data build upon the PCI-CURE substudy and the CREDO trial, which both showed pretreatment with clopidogrel was associated with a reduction in clinical events in non-ST elevation acute coronary syndromes and planned PCI, respectively. The present study is the first to demonstrate such a benefit in the setting of STEMI.
References:
Presented by Dr. Marc Sabatine at the European Society of Cardiology Hot Line Session, September 2005.
Sabatine MS, Cannon CP, Gibson CM, et al. Effect of clopidogrel pretreatment before percutaneous coronary intervention in patients with ST-elevation myocardial infarction treated with fibrinolytics: the PCI-CLARITY study. JAMA 2005;294:1224-32.
Keywords: Thrombolytic Therapy, Cytochrome P-450 Enzyme System, Myocardial Infarction, Stroke, Acute Coronary Syndrome, Platelet Aggregation Inhibitors, Ticlopidine, Blood Platelets, Fibrinolytic Agents, Angioplasty, Balloon, Coronary, Purinergic P2Y Receptor Antagonists, Prodrugs, Stents, Liver, Bundle-Branch Block
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