Not quite the full story on new antiplatelets

O’Sullivan and Tejani¹ provide an interesting perspective on our CMAJ review article.² Because of geographic differences in the efficacy of ticagrelor, the FDA delayed approval of the drug twice and requested further data and analysis.^3,4 Although the FDA document does identify some concerns, the manufacturer responses, an exhaustive review of additional data and reanalysis proved satisfactory for the FDA to finally approve ticagrelor in July 2011.

Not only do the Canadian Cardiovascular Society 2012 antiplatelet guidelines⁵ recommend prasugrel and ticagrelor over clopidogrel, but several other recent guidelines^6,7,8 also recommend ticagrelor over clopidogrel. These guidelines are very clear and transparent about how recommendations were synthesized, about methodology and about what evidence was included. These guidelines are targeted toward clinicians, thus having clinicians on the primary panel is appropriate.

O’Sullivan and Tejani¹ advocate that clinical trials need to be replicated, and that we can’t be certain of any early therapeutic benefit effect shown in only a single randomized controlled trial. Based on that premise, we should not be using aspirin for acute myocardial infarction. Twenty-five years ago, the landmark ISIS-2 trial showed the mortality benefit of early use of aspirin in acute myocardial infarction.⁹ This benefit has never been replicated in a randomized, properly powered clinical trial since ISIS-2.

We appreciate O’Sullivan and Tejani’s¹ concerns; however, no new drug or landmark trial is without its weaknesses and controversy. Clinicians should judge if the concerns surrounding the newer antiplatelet agents are sufficient to deny their patients more efficacious therapy.