Discussion
cardiovascular or respiratory organ, thrombosis, bleeding, critically ill, hyperreactive, platelet aggregation
THROMBOSIS, BLEEDING, CRITICALLY ILL, INFLAMMATION, COMPLICATIONS
In this open-label, international, multicenter, controlled platform randomized clinical trial of critically ill patients hospitalized for COVID-19, P2Y12 inhibitors did not significantly improve the composite of survival to hospital discharge or the number of days free of cardiovascular or respiratory organ support. The posterior probability of superiority for the primary end point was 73%, which did not meet the predefined criteria for superiority (>99% probability of OR >1). Survival to hospital discharge and through 90 days did not significantly differ with treatment assignment. Major bleeding complications were infrequent and balanced between the treatment groups.Platelets are hyperreactive and proinflammatory in COVID-19.The lack of demonstrable benefit of antiplatelet therapies in patients hospitalized for COVID-19 in previous trials could be partially explained by the testing of platelet inhibitors of multiple pathways (aspirin and P2Y12 inhibitors). We hypothesized that a focus on antagonism of the P2Y12 receptor pathway alone would be beneficial in patients with COVID-19 by modulating not only platelet aggregation and thrombosis but also platelet-mediated inflammation.An interesting finding in our subgroup analyses was that that participants 65 years or older appeared to have a worse outcome with P2Y12 inhibitors. In contrast, a potential benefit was observed in critically ill participants younger than 65 years. Increasing age is a major risk factor for bleeding