Summary
Recent European Society of Cardiology (ESC) Guidelines declare superiority of prasugrel
and ticagrelor over clopidogrel in non-ST segment elevation myocardial infarction
(NSTEMI) and STEMI patients with acute coronary syndromes (ACS). The recommendations
for NSTEMI and especially STEMI are based on a subgroup analyses yielded from a single
trial with either prasugrel (TRITON), or ticagrelor (PLATO). In contrast, the United
States (US) Guidelines present a more balanced, conservative, and evidence-based outlook
suggesting no proven extra benefit of one P2Y12 antagonist over the other(s). It was
the purpose of this study to scrutinise the evidence leading to the current ESC ACS
Guidelines on oral antiplatelet agents and compare them with US recommendations. Matching
the evidence from TRITON and PLATO primary publications with the data reported in
the Food and Drug Administration (FDA) official reviews in light of their impact on
current regional ACS Guidelines on antiplatelet P2Y12 inhibitors. The available body
of evidence on the efficacy and safety of the new oral P2Y12 inhibitors challenge
the ESC Guidelines, and supports the US recommendations. Some of the pivotal data
with regard to the newer P2Y12 inhibitors (prasugrel and ticagrelor) on event definition,
adjudication, questionable efficacy, and serious safety concerns were ignored by the
European Task Force Members, while the other “beneficial” findings were exaggerated
to a disproportional extent. We conclude that current ESC Guidelines, with regard
to their recommendation of superiority of prasugrel or ticagrelor over clopidogrel,
in contrast to the US, are overoptimistic, and not evidence based. Low clinical utilisation
of prasugrel and especially ticagrelor worldwide in general, and Europe in particular
suggests mismatch of prescription habits with issued ESC recommendations.
Keywords
Prasugrel - ticagrelor - clopidogrel - clinical trials - guidelines
