Does ICU Antiplatelet Therapy Improve Outcomes in COVID-19?

In critically ill patients with COVID-19, treatment with an antiplatelet agent appears to have a low likelihood of improving the number of organ support–free days within

21 days. Results from the Randomized, Embedded, Multifactorial Adaptive Platform Trial for Community-Acquired Pneumonia (REMAP-CAP; ClinicalTrials.gov identifier: NCT02735707) were recently published in Journal of the American Medical Association.

Trial investigators sought to establish whether the use of antiplatelet therapy (ie, P2Y12 inhibitors) improves outcomes among critically ill adult patients with COVID-19. The primary outcome of the ongoing, international study was organ support–free days (ie, the number of days patients went without intensive care unit–based respiratory or cardiovascular organ support) within 21 days. The range for number of days went from –1 for any in-hospital death to 22 for survivors with no organ support. Included among the 13 secondary study outcomes were survival to discharge and major bleeding to 14 days.

The study was designed to test the use of multiple interventions within multiple therapeutic domains. REMAP-CAP enrolled a total of 1557 critically ill patients with COVID-19 between October 30, 2020, and June 23, 2021, from 105 sites in 8 countries. Enrolled patients were followed for 90 days (final follow-up date of July 26, 2021). Participants were randomized to 1 of 3 groups: open-label aspirin (n=565), a P2Y12 inhibitor (n=455), or no antiplatelet therapy (control group; n=529).

Both the aspirin and the P2Y12 inhibitor arms fulfilled the predefined criteria for equivalence at an adaptive analysis and were statistically pooled for additional analysis. Enrollment was discontinued after the prespecified criterion for futility was satisfied for the pooled antiplatelet group compared with the control group.

Of the 1557 critically randomized patients, 8 withdrew consent; thus, a total of 1549 participants completed the trial. Overall, 33.6% of the participants were female. The median patient age was 57 years.

Results of the study revealed that the median for organ support–free days was 7

(range, –1 to 16) in both the antiplatelet arm and the control arm (median-adjusted odds ratio [OR], 1.02; 95% credible interval [CrI], 0.86-1.23; 95.7% posterior probability of futility).

The percentages of participants who survived to hospital discharge were 71.5% in the antiplatelet group compared with 67.9% in the control group (median-adjusted OR, 1.27; 95% CrI, 0.99-1.62; adjusted absolute difference, 5%; 95% CrI, –0.2% to 9.5%; 97% posterior probability of efficacy).

Among the survivors, the median number of organ support–free days was 14 in both the antiplatelet arm and the control arm. Major bleeding was reported in 2.1% of individuals in the antiplatelet group vs 0.4% of those in the control group (adjusted OR, 2.97; 95% CrI, 1.23 to 8.28; adjusted absolute risk increase, 0.8%; 95% CrI, 0.1% to 2.7%; 99.4% probability of harm).

Limitations of the current study include the fact that it used an open-label design, although the primary outcome of survival and need for organ support was chosen in an effort to minimize bias. Further, the use of a composite endpoint has the potential to identify different effects of the therapy on each component.

The investigators concluded that a low likelihood exists that treatment with an antiplatelet agent in critically ill patients with COVID-19 will be associated with any improvement in organ support–free days within 21 days.

Disclosure: Some of the study authors have declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures

Reference  

REM-CAP Writing Committee for the REM-CAP Investigators; Bradbury CA, Lawler PR, Stanworth SJ, et al. Effect of antiplatelet therapy on survival and organ support-free days in critically ill patients with COVID-19: a randomized clinical trial. JAMA. Published online March 22, 2022. doi:10.1001/jama.2022.2910