Advocates for pharmacogenomic implementation argue that what is known about clopidogrel bioactivation and the meta-analysis are sufficient to justify this approach now. Others argue that an RCT is required. One difficulty with conducting an RCT is that the effect size is likely to be greatest in homozygotes (rare group; e.g. <3% of subjects in PREDICT60) while that in heterozygotes is smaller. Further, randomizing homozygotes may be equivalent to administering placebo, and the resultant lack of clinical equipoise for some investigators may make randomization of homozygotes difficult. Nevertheless an RCT is underway but over the course of the study, newer stent technologies and newer antiplatelet drugs are becoming available.
