Anticoagulants associated with improved survival rates in people hospitalised with COVID-19

14 May 2020. Related: COVID-19: investigational drugs, COVID-19.

Simon Collins, HIV i-Base

A large retrospective analysis from researchers at Mount Sinai School of Medicine in New York reported that people hospitalised with COVID-19 who were treated with anticoagulant treatment (AC) had reduced mortality, but also higher rates of bleeding complications. [1]

Recent studies have reported increased cardiovascular complications including life-threatening clots in patients hospitalised with COVID-19, and post-mortem biopsies have reported blood clots in major organs, including lung and kidney tissue. [2, 3]

The current study involved 2773 participants hospitalised with confirmed COVID-19 between 14 March and 11 April 2020, 786 (28%) received oral, subcutaneous, or intravenous AC. The study is published as a research letter in the Journal of the American College of Cardiology.

Results were adjusted for age, sex, ethnicity, body mass index, history of hypertension, heart failure, atrial fibrillation, type 2 diabetes, AC use prior to hospitalisation, and admission date. AC treatment duration was used as a covariate while intubation was treated as a time-dependent variable.

The median time in hospital was 5 days (IQR: 3-8 days) and median time from admission to AC initiation was 2 days (IQR: 0-5 days). AC treatment lasted a median of 3 days (IQR: 2-7 days).

In-hospital mortality and median survival was 22.5% and 21 days, compared to 22.8% and 14 days in those with and without AC respectively. Participants receiving AC were more likely to require invasive mechanical ventilation (29.8% vs 8.1%, p<0.001).

In patients who required mechanical ventilation (N=395), in-hospital mortality and median survival was 29.1% and 21 days compared to 62.7% and 9 days, with vs without AC respectively. In multivariate analysis, longer duration of AC was associated with a reduced risk of mortality (adjusted HR of 0.86 per day, 95% confidence interval 0.82-0.89, p<0.001).

However, use of AC was also associated with higher rates of major bleeding events in 24 (3%) vs 38 (1.9%) in those with AC vs no AC respectively.

Of the 24 patients with bleeding events on AC, 15 (63%) had bleeding events after starting AC vs 9 (37%) before starting AC. Bleeding events were more common among patients intubated (30/395; 7.5%) than among non-intubated patients (32/2378; 1.35%).

The study concluded that AC was likely used for more severe clinical presentations and that AC was associated with improved survival after adjusting for mechanical ventilation, but that randomised studies were needed to confirm the results.

comment

A second study, also just published, in the 449 people with severe COVID-19 reported better outcomes in the 99 participants using anticoagulant therapy (mainly low molecular weight heparin). [4]

There was no overall difference in 28-day outcomes, but mortality was lower in people with sepsis-induced coagulopathy (SIC) score >4 (40.0% vs 64.2%, p=0.029), or D-dimer >6-fold of upper limit of normal (32.8% vs 52.4%, p=0.017).

This article was updated on 31 May 2020, to include the comment on the study by Tang et al.

References

1. Paranjpe I et al. Association of treatment dose anticoagulation with in-hospital survival among hospitalized patients with COVID-19. Journal of the American College of Cardiology, DOI: 10.1016/j.jacc.2020.05.001 (May 2020)
   http://www.onlinejacc.org/content/early/2020/05/05/j.jacc.2020.05.001
2. Lillicrap D. Disseminated intravascular coagulation in patients with 2019-nCoV pneumonia. J. Thromb. Haemost. 2020. DOI: 10.1111/jth.14781. (24 March 2020).
   https://onlinelibrary.wiley.com/doi/full/10.1111/jth.14781
3. Zhang Y et al. Coagulopathy and antiphospholipid antibodies in patients with Covid-19. N Engl J Med 2020; 382:e38. DOI: 10.1056/NEJMc2007575.(23 April 2020).
   https://www.nejm.org/doi/full/10.1056/NEJMc2007575
4. Tang N et al. Anticoagulant treatment is associated with decreased mortality in severe coronavirus disease 2019 patients with coagulopathy. Thromb Haemost . 2020,18(5):1094-1099. doi: 10.1111/jth.14817. (27 Apr 2020).
   https://pubmed.ncbi.nlm.nih.gov/32220112