Abstract 4450: Does the Evidence Support Guideline Recommendations for Clopidogrel Pretreatment?
Although few concrete data exist about the optimal timing and dose of clopidogrel pretreatment, the ACC/AHA & ESC guidelines endorse pretreatment with 300 – 600 mg of clopidogrel at least 2– 6 hours before PCI as Class IA (ACS) and Class IC (elective PCI) recommendation. To evaluate the current evidence base in support for clopidogrel pretreat-ment. Five trials examining the impact of clopidogrel pretreatment in stable and unstable CAD were evaluated: PCI-CURE, PCI-CLARITY, CREDO, PRAGUE-8, ARMYDA-5. Because of substantial clinical heterogeneity in trial design and population, concomitant therapies (glycoprotein 2b/3a inhibitors, thrombolysis, etc), loading dose, pretreatment duration and analysis plan between PCI-CURE, PCI-CLARITY and the rest, a formal meta-analysis was confined only to CREDO, PRAGUE-8, ARMYDA-5. The key data are summarized in the Table⇓. Clopidogrel pretreatment was associated with significant reduction in ischemic outcomes without a significant increase in major bleeding in two out of the 5 trials (PCI-CURE and PCI-CLARITY). Both these trials utilized nonrandomized subgroup comparisons with pretreatment duration longer than that typically encountered in clinical practice (<48h). A meta-analysis of the 3 trials demonstrated a nonsignificant 23% odds reduction in efficacy (P=0.1) and a nonsignificant 29% odds increase in major bleeding (P=0.24). No significant heterogeneity was observed for pooled efficacy (P=0.79) or bleeding (P=0.77) outcomes. Pretreatment hypothesis is currently not validated in rigorous prospective assessments, thereby calling into question the Class I recommendation (benefit >>>risk) endorsed by the guidelines. Clearly, further clinical data regarding dose, time course of pretreatment and associated benefit are warranted to provide unequivocal support. Until then, it is prudent to rule out surgical CAD before pretreatment to avoid bleeding risk.