Impact of oral anticoagulation on clinical outcomes of COVID-19: a nationwide cohort study of hospitalized patients in Germany

Clin Res Cardiol. 2021 Jul;110(7):1041-1050. doi: 10.1007/s00392-020-01783-x. Epub 2021 Jan 8.


Objectives: The aim of this study was to investigate the impact of concomitant long-term medication-with a focus on ACE inhibitors and oral anticoagulation-on clinical outcomes in patients hospitalized with coronavirus disease 2019.

Methods: This is a retrospective cohort study using claims data of the biggest German health insurance company AOK, covering 26.9 million people all over Germany. In particular, patient-related characteristics and co-medication were evaluated. A multivariable logistic regression model was adopted to identify independent predictors for the primary outcome measure of all-cause mortality or need for invasive or non-invasive ventilation or extracorporeal membrane oxygenation.

Results: 6637 patients in 853 German hospitals were included. The primary outcome occurred in 1826 patients (27.5%). 1372 patients (20.7%) died, 886 patients (13.3%) needed respiratory support, and 53 patients (0.8%) received extracorporeal membrane oxygenation. 34 of these patients survived (64.2%). The multivariable model demonstrated that pre-existing oral anticoagulation therapy with either vitamin-K antagonists OR 0.57 (95% CI 0.40-0.83, p = 0.003) or direct oral anticoagulants OR 0.71 (95% CI 0.56-0.91, p = 0.007)-but not with antiplatelet therapy alone OR 1.10 (95% CI 0.88-1.23, p = 0.66)-was associated with a lower event rate. This finding was confirmed in a propensity match analysis.

Conclusions: In a multivariable analysis, a therapy with both direct oral anticoagulants or vitamin-K antagonists-but not with antiplatelet therapy-was associated with improved clinical outcomes. ACE inhibitors did not impact outcomes. Prospective randomized trials are needed to verify this hypothesis.

Keywords: ACE inhibitors; Antiplatelet therapy; COVID-19; DOACs; ECMO; Vitamin-K-antagonist.

MeSH terms

  • Administration, Oral
  • Aged
  • Aged, 80 and over
  • Angiotensin-Converting Enzyme Inhibitors / administration & dosage*
  • Anticoagulants / administration & dosage*
  • COVID-19 / mortality
  • COVID-19 / physiopathology
  • COVID-19 / therapy*
  • Cohort Studies
  • Extracorporeal Membrane Oxygenation
  • Female
  • Germany
  • Hospitalization*
  • Humans
  • Male
  • Middle Aged
  • Outcome Assessment, Health Care
  • Platelet Aggregation Inhibitors / administration & dosage
  • Respiration, Artificial
  • Retrospective Studies


  • Angiotensin-Converting Enzyme Inhibitors
  • Anticoagulants
  • Platelet Aggregation Inhibitors