Pharmacoinvasive Management of Acute Coronary Syndrome in the Setting of Percutaneous Coronary Intervention: Evidence-Based, Sit
- Volume 15 - Issue 11 - November, 2003
- Posted on: 8/1/08
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The primary study endpoint (a composite of death from cardiovascular causes, nonfatal MI or stroke) occurred in 9.3% of the patients in the clopidogrel plus aspirin group and 11.4% of the patients in the aspirin only group (RR with clopidogrel as compared with placebo, 0.80; 95% CI, 0.72–0.90; p < 0.001). The key secondary endpoint, a composite of the primary endpoint or severe refractory ischemia, occurred in 16.5% of the patients treated with clopidogrel and in 18.8% of patients receiving aspirin only (RR, 0.86; p < 0.001). The percentage of patients with major bleeding events was greater in the clopidogrel group (RR, 1.38), although the percentage of patients with life-threatening bleeding events was similar between groups.45 Among 2,568 patients undergoing PCI in the CURE study, pretreatment with clopidogrel was also beneficial.50 A clopidogrel oral loading dose (300 mg) for appropriately selected ACS patients is recommended. This dose provides measurable platelet inhibition within 2 hours compared with more than 6 hours without the loading dose.51
It should be emphasized that not all patients are appropriate candidates for clopidogrel. Transfusion requirements are increased by clopidogrel treatment. The CURE study provides strong evidence for the addition of clopidogrel to aspirin in the ED as part of overall management for patients with ACS, in whom CABG is contraindicated or in whom a noninterventional approach is intended. However, major, life-threatening bleeds are more frequent when patients undergo CABG within 5 days of their last dose of clopidogrel (OR, 1.50). There is no increased perioperative bleeding in those who can be taken off clopidogrel for at least 5 days. Although PCI-CURE and the CREDO trials support pretreatment with clopidogrel in patients undergoing PCI, a reasonable approach for patients with unstable angina/NSTEMI who undergo diagnostic catheterization within 24–36 hours of admission is to administer clopidogrel once it is clear that CABG will not be imminently scheduled.50,52 A loading dose of clopidogrel can be given to a patient at the time of catheterization if PCI is to be carried out, although pretreatment for 6 or more hours may improve outcomes.52 If PCI or CABG is not performed (medical therapy only), clopidogrel can be administered after the catheterization.
From a practical, time-of-administration perspective, because clopidogrel increases the risk of intra- and peri-operative hemorrhage in patients undergoing CABG surgery, the decision to initiate clopidogrel therapy in the ED (prior to PCI), at the time of PCI (in the cath lab), or after PCI in patients with ACS should be based primarily on whether the patient is likely to undergo CABG surgery. The Panel recommends that whenever possible in patients who undergo PCI, clopidogrel should be administered on the cath table before device activation. Patients managed in settings where PCI and CABG facilities are available, or for whom transfer to such sites is routine, may have clopidogrel therapy delayed until the coronary anatomy is defined and the decision to proceed or not proceed with CABG surgery has been made.