a p w b e p “ S b s “ t a s i n i v t p m d e o n s u a b o b b S f d v r p e w a a ( r d p d Q v f t o w o Numerous randomized trials have indicated the benefits f clopidogrel either as an alternative1 or as an adjunct2 to spirin for the secondary prevention of acute vascular vents, including absolute mortality reduction in the largest ver acute myocardial infarction study.3 Despite proved fficacy, antiplatelet protection with clopidogrel has several otential limitations, such as delayed onset of platelet inhiition even after loading regimens,4,5 substantial response ariability in the acute setting,6,7 remaining risk for the evelopment of vascular thrombosis,8,9 and higher rates of erioperative bleeding complications during cardiac surery10,11 because of the irreversible nature of platelet P2Y12 eceptor blockade. It is unclear to what extent clopidogrel er se is responsible for all these shortcomings, how damging are they in real-life clinical scenarios, and, most mportant, what can be done to prevent, minimize, or comensate for such limitations. All real or perceived limitaions associated with response to clopidogrel can be divided nto 2 categories: those driven by measuring multiple bimarkers in the platelet studies (the variability and durabilty of response, excess timing needed to exhibit full-scale ntiplatelet potency, and inefficient inhibition due to inreased baseline preexisting platelet activity) and those scearios really observed in clinical practice (recurrent vascuar events, including stent thrombosis, and increased leeding risks). Insufficient platelet inhibition with clopiogrel has been termed “clopidogrel resistance.” However, uch “resistance” still remains a laboratory research finding ather than a proved, clinically relevant fact, despite numerus attempts to link low response to clopidogrel with worsned vascular outcomes12,13 in general and the development f stent thrombosis14,15 in particular. All these small studies all short of proving that changes in certain platelet biomarers may predict outcomes after clopidogrel, because they re overpowered by discrepancies with available randomzed clinical data and contradicting epidemiologic evidence. It seems that noncompliance is a major and the most ogical practical reason for nonresponse to clopidogrel. ith regard to compliance, it is critical to divide the evience into acute (in-hospital) and maintenance (outpatient) ong-term settings. In fact, clopidogrel administration is ontrolled much better in the hospital than in outpatients. herefore, platelet data suggesting “resistance” may have erit when properly assessed during loading regimens beause clopidogrel is indeed on board. However, these studes cannot overcome the power and validity of the Clopiogrel and Metoprolol in Myocardial Infarction Trial COMMIT),3 in which a combination of moderate-dose