Not quite the full story on new antiplatelets/The authors respond

[Doson Chua] and Nishi1 did not reference the US Food and Drug Administration (FDA) medical review of ticagrelor.2 This comprehensive review considered both published and unpublished data from the PLATO trial. The FDA reviewers identified that the reduction in mortality reported by Chua and Nishi1 was present only in the non-US population, thus limiting the generalizability of this finding. Reviewers also identified irregularities surrounding the ascertainment of outcomes and participant follow-up times. Also, FDA reviewers state "[a] troubling observation in PLATO was the increased frequency and earlier time to overall stroke and intracranial hemorrhagic bleeding events (mostly from strokes) in the ticagrelor-treated patients ... and the relative risk of having a stroke or TIA for patients with pre-existent disease was 2 times higher for ticagrelor-treated patients than for clopidogrel-treated patients." The FDA medical review of prasugrel3 was also omitted from Chua and Nishi's1 assessment. Several important safety signals arise from the FDA analysis. Chua and Nishi1 indicate that support for the new antiplatelets comes from "recent clinical guidelines." To characterize guidelines as supportive evidence is misleading, particularly when the cited guidelines4 do not report involving methodology experts in their primary guideline panel.5 Our final concern rests with the authors'1 seemingly definitive recommendations. The authors conclude that ticagrelor and prasugrel have a role in acute coronary syndrome, despite the fact that there is only one randomized controlled trial (RCT) for ticagrelor and two discordant RCTs for prasugrel. We suggest a more cautious conclusion is appropriate, namely that there is insufficient evidence for prasugrel and ticagrelor to rule out serious harm or to characterize the benefit in patients with acute coronary syndrome.