Infectious Disease

Antiplatelet agents fail to benefit critically ill adults with COVID-19

March 22, 2022

2 min read

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Disclosures:
Bradbury reports receiving personal fees from Ablynx, Amgen, Bayer, Bristol Myers Squibb/Pfizer, Eli Lilly, Grifols, Janssen, Novartis and Portola. Please see the study for all other authors’ relevant financial disclosures. Connors reports receiving an institutional research grant from CSL Behring and consulting and/or serving on advisory boards for Alnylam, Bristol Myers Squibb, Five Prime Therapeutics, Pfizer, Roche, Sanofi and Takeda. Ridker reports receiving grant support from Amarin, the Baim Institute, Boehringer Ingelheim, Esperion, Kowa, Novartis and Pfizer and consulting for Agepha, Alnylam, AstraZeneca, Civi Biopharm, Flame, Health Outlook, Horizon Therapeutics, Inflasome, IQVIA, Janssen, Novartis, Novo Nordisk, Omeicos, RPharma, SOCAR and Uptton.

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Compared with no antiplatelet therapy, aspirin and P2Y12 inhibitors did not improve the number of organ support-free days in critically ill patients with COVID-19, according to results of the REMAP-CAP trial published in JAMA.

The researchers enrolled 1,557 critically ill patients with COVID-19 (median age, 57 years; 34% women) in the REMAP-CAP ongoing adaptive platform trial. Patients were randomly assigned aspirin, a P2Y12 inhibitor, or no antiplatelet therapy for a maximum of 14 days on top of anticoagulation thromboprophylaxis.

Graphical depiction of data presented in article

Data were derived from REMAP-CAP Writing Committee for the REMAP-CAP Investigators. JAMA. 2022;doi:10.1001/jama.2022.2910.

The primary endpoint was number of organ support-free days, defined as being alive and free from ICU-based CV or respiratory organ support, at 21 days.

The aspirin group and the P2Y12 inhibitor group met the prespecified criteria for equivalence and were pooled for comparison to the control group, the researchers wrote.

No net benefit

Charlotte A Bradbury

The median number of organ support-free days for both the antiplatelet and control groups was 7 (interquartile range, -1 to 16; median-adjusted OR = 1.02; 95% credible interval [CrI], 0.86-1.23; posterior probability of futility, 95.7%), Charlotte A Bradbury, MD, PhD, from the Bristol Haematology and Oncology Centre, Bristol, UK, and colleagues wrote.

Among the antiplatelet cohort, 71.5% survived to hospital discharge compared with 67.9% of 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 ; posterior probability of efficacy, 97%), the researchers wrote.

In both groups, among patients who survived, the median number of organ support-free days was 14.

“The reduction in mortality was counterbalanced by an increase in the number of patients receiving short durations of organ support (< 6 days), resulting in an overall net neutral effect on the outcome of organ support–free days,” the researchers wrote.

Major bleeding occurred in 2.1% of the antiplatelet group and 0.4% of the control group (adjusted OR = 2.97; 95% CrI, 1.23-8.28; adjusted absolute risk increase, 0.8%; 95% CrI, 0.1-2.7; probability of harm , 99.4%), Bradbury and colleagues wrote.

“It is possible that antiplatelet therapy may reduce fatal complications of COVID-19 in critically ill patients while potentially increasing the need for organ support, possibly through bleeding that may or may not be clinically evident, such as alveolar hemorrhage,” the researchers wrote. “Major bleeding occurred more frequently in patients randomized to antiplatelet therapy. It is also possible that the net neutral effect of antiplatelet therapy on organ support-free days may have been influenced by a harmful interaction between antiplatelet therapy and therapeutic-dose anticoagulation, whereby patients receiving the combination appeared to have worse outcomes.”

‘No proven efficacy’

Paul M. Ridker

In a related editorial, Jean M. Connors, MD, hematologist at Brigham and Women’s Hospital and associate professor of medicine at Harvard Medical School, and Paul M. Ridker, MD, MPH, director of the Center for Cardiovascular Disease Prevention at Brigham and Women’s Hospital and Eugene Braunwald Professor of Medicine at Harvard Medical School, wrote that REMAP-CAP is the latest of several trials to demonstrate that a net hazard is produced when antiplatelets are added to anticoagulation alone in patients with COVID-19.

“The accumulated data should provide physicians with the rare confidence to do less rather than more, a finding that also has become apparent with anticoagulation therapy,” Connors and Ridker wrote.

“At this juncture in the global pandemic, all hospitalized patients with COVID-19 and low risk of bleeding should receive at least prophylactic dose anticoagulation with a heparin anticoagulant, with consideration of therapeutic dose heparin in some cases, but there is no proven efficacy supporting the addition of traditional antiplatelet therapies to prevent progressive thromboinflammatory complications of COVID-19,” they wrote. “The clinical goal, however, should be to avoid thromboinflammation and hospitalization in the first place, an objective largely achievable through aggressive vaccination.”

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