Early initiation of anticoagulation may prevent death in COVID-19 patients

Patients with COVID-19 who received prophylactic anticoagulation within 24 hours of admission have a much lower risk of 30-day mortality and no increased risk of serious bleeding events compared to those with no anticoagulation, a study has shown. Moreover, this benefit appears greater among patients not admitted to the intensive care unit.

“Our results provide strong real-world evidence to support guidelines recommending the use of prophylactic anticoagulation as initial treatment for patients with COVID-19 on hospital admission,” the researchers said.

This observational cohort study included 4,297 patients admitted to a hospital from 1 March to 31 July 2020 with laboratory-confirmed SARS-CoV-2 infection, the causative agent of COVID-19, and without a history of anticoagulation.

A total of 3,627 (84.4 percent) received prophylactic anticoagulation within 24 hours of admission, of whom 3,600 (99 percent) were treated with subcutaneous heparin or enoxaparin. There were 622 deaths reported within 30 days of hospital admission, of which 513 had received prophylactic anticoagulation. Most deaths (82 percent) occurred during hospital stay. [BMJ 2021;372:n311]

Inverse probability of treatment weighted analyses revealed a 14.3-percent (95 percent confidence interval [CI], 13.1–15.5) cumulative incidence of 30-day mortality among patients who received prophylactic anticoagulation and 18.7-percent (95 percent CI, 15.1–22.9) incidence among those who did not. Patients with vs without prophylactic anticoagulation had a 27-percent lower risk of 30-day mortality (hazard ratio [HR], 0.73, 95 percent CI, 0.66–0.81).

Similar associations were observed between initiation of therapeutic anticoagulation and inpatient mortality. In addition, initiation of prophylactic anticoagulation did not increase the risk of bleeding requiring transfusion (HR, 0.87, 95 percent CI, 0.71–1.05).

Results were robust to unmeasured confounding in quantitative bias analysis and persisted in several sensitivity analyses.

Previous studies examining the role of anticoagulation in patients with COVID-19 showed varying results. [J Am Coll Cardiol 2020;76:1815-1826; J Thromb Haemost 2020;18:1094-1099; Front Pharmacol 2020;11:1124; J Am Coll Cardiol 2020;76:122-124; Am J Cardiol 2020;134:155-157; Clin Appl Thromb Hemost 2020;26:1076029620960797; Eur J Intern Med 2020;77:158-160]

“Variations in reported associations probably derive from different definitions of anticoagulation, for both drug type and dose,” the researchers said. “Additionally, different patient populations (eg, disease specific cohorts), comparator groups, and inclusion and exclusion criteria were used.”

In the context of COVID-19, thromboembolic events were more likely to result in death. While the cause of elevated thrombosis risk remains unclear, certain mechanisms have been proposed, including systemic inflammation, endothelialitis, and activation of the complement system. [J Clin Pharmacol 2020;60:1411-1415; Circulation 2020;142:114-128; JAMA 2020;324:799-801; Thromb Res 2020;196:483-485; Nature 2020;588:146-150; N Engl J Med 2020;383:120-128; Mol Biol Rep 2020;47:8301-8304]

Furthermore, heparin has been shown to block the SARS-CoV-2 viral spike protein from binding in experimental studies. [Br J Pharmacol 2021;178:626-635; J Virol 2021;95:e01987-20; Cell 2020;183:1043-1057.e15]

“We postulate that the combination of the known antithrombotic and potential anti-inflammatory effects of heparin, in addition to attenuation of viral infectivity might, at least in part, explain the observed benefit associated with prophylactic anticoagulation,” the researchers said. [Iran J Pharm Res 2014;13:583-590; Adv Pharmacol Sci 2015;2015:507151]