P2Y12 inhibitors not found to be effective for critically ill patients with COVID-19

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1. For critically ill patients hospitalized for COVID-19, P2Y12 inhibitors did not improve organ support-free days or survival to discharge compared to usual care. 

Evidence Rating Level: 1 (Excellent)

Antiplatelet therapy has been proposed in the management of critically ill COVID-19 patients, as platelets play a prothrombotic and proinflammatory role, in patients who are already at high risk of vasculopathy and thrombotic events. Prior studies suggested that antiplatelet therapy did not decrease the risk of requiring organ support, and had no benefit in noncritically ill COVID-19 patients. Therefore, this international controlled platform randomized controlled trial evaluated the impact of P2Y12 inhibitors on morbidity and mortality in critically ill COVID-19 patients, compared to care as usual. In this study, critically ill referred to patients that required intensive care. Patients were randomized 1:1 to receive a P2Y12 inhibitor, either ticagrelor or clopidogrel, or to usual care with no P2Y12 inhibitor. The duration of therapy was the earliest of either 14 days or discharge. The primary outcome was the organ support-free days, which was a composite of survival to discharge and number of days without cardiac or respiratory organ support up to day 21 of hospitalization. In total, there were 479 patients in the P2Y12 inhibitor group and 470 in usual care. The results showed a median (IQR) organ support-free days of 12 (-1 to 17) and 11 (-1 to 18) in the P2Y12 inhibitor and usual care groups respectively (adjusted odds ratio 1.07, 95% CrI 0.85-1.33, posterior probability of superiority 72.9%). Additionally, 74.5% and 72.4% of patients survived to discharge in the P2Y12 inhibitor and usual care groups respectively. There was also no difference in major thrombotic events or death in-hospital, at 28.2% for the P2Y12 inhibitor cohort versus  25.7% in usual care (aOR 1.10, 95% CI 0.81-1.50). Lastly, the rate of major bleeding was also similar between the cohorts, affecting 1.0% in the P2Y12 inhibitor and 0.4% of the usual care groups respectively (aOR 2.33, 95% CI 0.45-12.2). Overall, this study showed that P2Y12 inhibitor therapy did not improve organ support-free days or survival to discharge, for critically ill COVID-19 patients.

Click to read the study in JAMA Network Open

Image: PD

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