Full-Dose Anticoagulation Lowers Thrombotic Event Risk in Patients with COVID-19

David Berg, MD

New findings suggest full-dose anticoagulation lowered the risk of venous and arterial complications by 44% compared with the standard-dose treatment of critically ill patients with COVID-19.

Additional treatment with clopidogrel led to no difference in the risk of clotting complications or of fatal or life-threatening bleeding when compared with no antiplatelet therapy in this patient population.

The findings were presented in a Hot Line session at the European Society of Cardiology Congress 2022.

Presenting author David Berg, MD, Brigham and Women’s Hospital noted in a statement that COVID-19 treatment guidelines have left clinicians confused, as current recommendations suggest full-dose anticoagulation for hospitalized patients outside the intensive care unit (ICU) and standard dose for individuals in the ICU.

“COVID-PACT shows that full-dose anticoagulation more effectively prevents the clotting complications of COVID-19, which may be a more appropriate focus for antithrombotic therapy as a preventive intervention, and is the basis for anticoagulation recommendations in ICU patients without COVID-19,” Berg added.

The randomized, 2x2 factorial COVID-PACT trial evaluated the intensity of anticoagulation and the usage of antiplatelet therapy for the prevention of venous and arterial thrombotic events in critically ill patients with COVID-19.

The trial randomized patients (≥18 years old) with an acute infection with SARS-CoV2 requiring ICU level of care at 34 sites in the United States in a 1:1 ratio to full-dose or standard-dose prophylactic anticoagulation. For those without another indication for antiplatelet therapy, there was a secondary randomization to either clopidogrel or no antiplatelet therapy.

Its primary efficacy outcome was defined as a hierarchical composite of venous and arterial thrombotic events through hospital discharge or 28 days, including:

• Death
• Pulmonary embolism
• Clinically evident deep vein thrombosis (DVT)
• Type 1 myocardial infarction (MI)
• Ischemic stroke
• Systemic embolic event (SEE) or acute limb ischemia (ALI)
• Clinically silent DVT

From August 2020 through March 2022, a total of 390 patients were randomized between anticoagulation strategies and 292 were randomized between antiplatelet strategies. The on-treatment analysis included 382 patients and 290 patients, respectively. Almost all patients (99%) required advanced respiratory therapy.

Berg and colleagues reported a greater proportion of wins occurred for the primary efficacy endpoint in the full-dose anticoagulation group (12.3%) compared to the standard-dose prophylactic anticoagulation (6.4%; win ratio, 1.95; 95% confidence interval [CI], 1.08 - 3.55; P = .028).

The findings were consistent in the time-to-event analysis for the primary endpoint. In the full dose anticoagulation cohort, 19 of 191 patients (9.9%) experienced a primary endpoint event compared with 29 of 181 (15.2%) patients in the standard-dose group (hazard ratio [HR], 0.56; 95% CI, 0.32 - 0.99; P = .046).

Primary safety outcomes of fatal or life-threatening bleeding occurred in 4 patients (2.1%) on full-dose anticoagulation and 1 patient (0.5%) on standard-dose anticoagulation (P = .19).

There were no observed differences in all-cause mortality between groups and no differences in primary efficacy or safety endpoints with clopidogrel compared with no antiplatelet therapy.

The study, “Anticoagulation and Antiplatelet Therapy for Prevention of Venous and Arterial Thrombotic Events in Critically Ill Patients with COVID-19: COVID-PACT,” was published in Circulation.