Increasing Doses of Anticoagulation Are Associated with Improved Survival in Hospitalized COVID-19 Patients

Abstract

Background: Hypercoagulability may contribute to COVID-19 pathogenicity. Evidence comparing clinical outcomes among patients with COVID-19 receiving therapeutic compared to prophylactic dose anticoagulation is limited. We evaluated whether therapeutic anticoagulation (tAC) is associated with improved survival compared to prophylactic (pAC) and no anticoagulation (AC) in hospitalized COVID-19 patients. Methods: This was a retrospective, multi-center cohort study of consecutive COVID-19 patients admitted between March 13th, 2020 and May 5th, 2020 to eight hospitals within a large academic system in Southeast Michigan, USA. Participants were assigned to three groups based on whether they received no AC, pAC throughout most of their hospitalization, or at least 3 days of tAC. Major bleeding was defined as transfusion of five or more units of packed red blood cells within 48 hours regardless of hemoglobin level, hemoglobin < 7g/dL and any red blood cell transfusion or a diagnosis code for major bleeding during the hospitalization or radiological evidence of intracranial hemorrhage Results: A total of 3480 patients were included (mean age, 64.5 years [17.0]; 51.5% female; 52.1% black and 40.6% white). 18.5% (n=642) were treated in the intensive care unit (ICU). 60.9% received pAC (n=2121), 28.7% received at least 3 days of tAC (n=998), and 10.4% (n=361) did not receive AC. Propensity score (PS) weighted Kaplan-Meier plot demonstrated a statistical difference in the 25-day survival probability in the tAC group compared to the pAC group (57.5% vs 50.7%, Figure). In a PS weighted multivariate proportional hazards model adjusting for age, body mass index and ICU status, AC was associated with a reduced risk of death at both prophylactic (hazard ratio [HR] 0.35 [95% confidence interval {CI} 0.22-0.54]) and therapeutic doses (HR 0.14 [95% CI 0.05-0.23]) compared to no AC. Major bleeding occurred more frequently among tAC patients (81 [8.1%]) compared to those who received no AC (20 [5.5%]) or pAC (46 [2.2%]). Conclusions : Higher doses of AC are associated with lower mortality in hospitalized COVID-19 patients. The lowest hazard ratio was observed in ICU patients, but risk was also significantly lower in non-ICU hospitalized patients. Bleeding occurred more frequently with higher doses of anticoagulation. Ongoing randomized trials are warranted to prospectively evaluate efficacy and risk of tAC in patients with COVID-19. Figure Disclosures No relevant conflicts of interest to declare.

Intermediate‐dose anticoagulation, aspirin, and in‐hospital mortality in COVID‐19: A propensity score‐matched analysis

“…[43][44][45] Retrospective studies of therapeutic-compared to prophylactic-dose anticoagulation have reported mixed effects on mortality, while only two small studies have examined outcomes with intermediate-compared to prophylactic-dose anticoagulation, largely focusing on venous thromboembolism rates, again with conflicting results. 7,15,16,[18][19][20][21][22]46,47 More recently, the ACTIV-4a randomized clinical trial showed efficacy of therapeutic-compared to prophylactic-dose anticoagulation in noncritically ill COVID-19 patients but futility among critically ill patients. 23,24 Our analysis is the first large-scale study to specifically examine intermediate-and prophylactic-dose anticoagulation in COVID-19.…”

“…13,14 Some retrospective studies have observed lower mortality rates with therapeutic-dose anticoagulation compared to either prophylacticdose anticoagulation or no anticoagulation, while others comparing therapeutic-and prophylactic-dose anticoagulation have found no mortality difference. [15][16][17][18][19][20][21][22] Recent findings from the ACTIV-4a randomized controlled trial showed that therapeutic-compared to prophylactic-dose anticoagulation improved outcomes among non-critically ill patients but not among critically ill COVID-19 patients. 23,24 To date, however, no large-scale study has compared the effects of intermediate-versus prophylactic-dose anticoagulation.…”