Clinical Question

Do anticoagulants reduce the risk of venous thromboembolism or mortality in people hospitalized with COVID-19?

Evidence-Based Answer

In people hospitalized with COVID-19, the use of anticoagulants reduces all-cause mortality (number needed to treat [NNT] = 9; 95% CI, 7.3 to 13). Using a higher dose of anticoagulants may reduce the risk of pulmonary embolism (PE) compared with a lower dose of the same agent (NNT = 56; 95% CI, 44 to 100). Using a higher dose also increases the risk of major bleeding (number needed to harm [NNH] = 100; 95% CI, 42 to 1,000) and minor bleeding (NNH = 50; 95% CI, 10 to 67).¹ (Strength of Recommendation: B, inconsistent or limited-quality patient-oriented evidence.)

Practice Pointers

All patients with COVID-19 are at risk of thromboembolic complications, including deep venous thrombosis (DVT) and PE, and bleeding complications.² In patients hospitalized with COVID-19, rates of DVT (up to 14.8%) and PE (up to 16.5%) are much higher than rates of DVT and PE in hospitalized patients in the United States (0.15% for DVT and 0.1% for PE).^3,4 Clotting and bleeding complications associated with COVID-19 may be caused by dysregulation of the coagulation cascade in response to viral infection.⁵ The authors of this Cochrane review sought to clarify the benefits and risks of anticoagulation for persons hospitalized with COVID-19.

The review included three nonrandomized studies comparing anticoagulation vs. no anticoagulation and four randomized controlled trials (RCTs) comparing lower vs. higher doses of anticoagulants.¹ Two studies were from Brazil, one from Iran, one from Italy, one from the United States, and two from multiple countries. All seven studies included patients from emergency department, inpatient ward, and intensive care unit settings.

Three studies compared anticoagulation, including low-molecular-weight heparin (LMWH), unfractionated heparin, fondaparinux (Arixtra), direct oral anticoagulants (DOACs), and oral vitamin K antagonists, with no treatment using prophylactic dosing, although 15% of patients in one study received a therapeutic dose of LMWH. Two of the three studies were categorized as being at critical risk of bias because of patient selection and confounding. Although very low-quality evidence causes uncertainty about whether anticoagulants for hospitalized patients with COVID-19 have any effect on the individual outcomes of DVT, PE, or bleeding compared with no anticoagulants, the three studies together suggest that they may reduce all-cause mortality over 15 to 30 days of follow-up (NNT = 9; 95% CI, 7.3 to 13).

Four RCTs compared higher doses of heparins or DOACs with lower doses. There was no evidence of a reduction in all-cause mortality with higher vs. lower doses at 30 or 90 days of follow-up. The low-quality evidence leaves it uncertain whether higher doses of anticoagulants have any effect on the need for additional respiratory support or risk of DVT. However, there is moderate-quality evidence that higher doses of anticoagulants reduce the risk of PE (NNT = 56; 95% CI, 44 to 100) at the cost of increased risk of major bleeding (NNH = 100; 95% CI, 42 to 1,000) over 28 to 30 days of follow-up. There is high-quality evidence from three RCTs that higher doses of anticoagulants increase the risk of minor bleeding (NNH = 50; 95% CI, 10 to 67) over 28 to 30 days of follow-up.

The American College of Chest Physicians (CHEST) recommends anticoagulation with therapeutic doses of unfractionated heparin or LMWH for acutely ill patients hospitalized with COVID-19 at low risk of bleeding, and it recommends prophylactic dosing for all other patients. For critically ill patients with COVID-19, CHEST recommends prophylactic doses of unfractionated heparin or LMWH.⁶

The practice recommendations in this activity are available at https://www.cochrane.org/CD013739.

Editor's Note: The CIs and NNTs reported in this Cochrane for Clinicians were calculated by the author based on raw data provided in the original Cochrane review.