The TRITON versus PLATO trials: differences beyond platelet inhibition

Clopidogrel monopoly as an exclusive oral antiplatelet agent used in combination with aspirin or as a monotherapy for treatment or/and prevention of occlusive thrombotic vascular events has been recently challenged. Based on the indirect comparison of TRITON and PLATO trial data, ticagrelor is clearly superior to prasugrel in a population of patients with acute coronary syndrome (ACS) because of absolute mortality reduction, realistic second myocardial infarction (MI) prevention, growing over time vascular outcome benefit, fewer haemorrhagic fatalities, potentially less coronary artery bypass graft (CABG)- related bleeding events, and lack of cancer risks. Despite an unfavourable immediate safety profile, ticagrelor has a lot of room to compensate for agitation, dyspnea, and ventricular pauses, if used in appropriate patients. It will be naïve and wrong to assume that ticagrelor will completely substitute clopidogrel, especially considering higher discontinuation rates after ticagrelor, generic competition, and other health economics issues. However, unless the regulatory authorities discover some unexpected serious flaws with PLATO, the ticagrelor will substantially change the present landscape of oral antiplatelet therapy, especially in high-risk patients, diabetics, and those with repeated vascular events including stent thrombosis. In contrast, a too exclusive trial design, a lack of persistent vascular benefit despite issues with event adjudication, growing-over-time bleeding complications, an issue with cancer, and finally an increase in mortality risk among unstable angina and non ST-elevated myocardial infarction will likely prevent a broad prasugrel implementation, unless more reassuring evidence becomes available.