Direct-acting oral anticoagulants use prior to COVID-19 diagnosis and associations with 30-day clinical outcomes

Abstract

Background It is unclear if direct-acting oral anticoagulants (DOACs) use before hospitalization due to COVID-19 diagnosis would potentially impact the severity and clinical outcomes thereafter. We compared 30-day hospitalization/re-hospitalization and clinical outcomes between patients on chronic DOAC therapy and patients not on oral anticoagulation (OAC) therapy at time of COVID-19 diagnosis. Methods We used data from TriNetX, a global federated health research network. Patients aged ≥18 years who were treated with DOACs at time of COVID-19 diagnosis between 20 January 2020 and 28 February 2021 were included, and matched with patients not on OAC therapy from the same period. All patients were followed-up at 30-days after COVID-19 diagnosis. The primary outcomes were all-cause mortality, hospitalization/re-hospitalization, venous thromboembolism (VTE) and intracranial hemorrhage (ICH). Results 738,423patients were included. After propensity score matching (PSM), 26,006 patients remained in the study (13,003 on DOACs; 13,003 not on OAC). DOAC-treated patients (mean age 67.1 ± 15.4 years, 52.2% male) had higher relative risks (RRs) and lower 30-days event-free survival as compared to patients not on OAC for all-cause mortality (RR 1.27, 95% CI 1.12–1.44; Log-Rank test p = 0.010), hospitalization/re-hospitalization (RR 1.72, 95% CI 1.64–1.82; Log-Rank test p < 0.001) and VTE (RR 4.51, 95% CI 3.91–5.82; Log-Rank test p < 0.001), but not for ICH (RR 0.90, 95% CI 0.54–1.51; Log-Rank test p = 0.513). Conclusion In COVID-19 patients, previous DOAC therapy at time of diagnosis was not associated with improved clinical outcomes or lower hospitalization/re-hospitalization rate compared to patients not taking OAC therapy.

2021 Focused Update Consensus Guidelines of the Asia Pacific Heart Rhythm Society on Stroke Prevention in Atrial Fibrillation: Executive Summary

“…195 For patients already treated with NOACs or VKA and infected with COVID-19 and particularly in the case of severe infection requiring hospitalization, patients should ideally continue their anticoagulation rather than discontinue, although outcome data are conflicting. 196 197 198 199 …”

ISTH guidelines for antithrombotic treatment in COVID‐19

“… 13 One RCT and two cohort studies on antiplatelet agents and oral anticoagulants did not demonstrate any benefit of prescribing these agents after diagnosis of COVID‐19. 9 , 10 , 11 A single study that used a randomized control design, showed that the glycosaminoglycan oral drug sulodexide may reduce risk of hospitalization and possibly also the need for oxygen supplementation. 12 These results need to be confirmed in future studies.…”

“… 17 Two large cohort studies of outpatients with cardiovascular disease, who were mostly on direct oral anticoagulants (DOACs), did not show reduced risk of hospitalization, death, or thrombosis. 10 , 11 However, in the larger of the two studies, no minimum exposure to outpatient oral anticoagulation was required, nor was there adjustment for in‐hospital treatments. 10 A population‐based outpatient cohort study found a small increase in mortality risk among those on pre‐existing oral anticoagulation, but there was no adjustment for in‐hospital treatments or antithrombotic regimen modification.…”

“… 18 Only one cohort study reported bleeding events, showing an infrequent, but statistically significantly increased risk of bleeding in anticoagulated patients. 10 , 11 , 16 , 17 , 18 Although current evidence does not support initiation of DOACs among outpatients with COVID‐19, there is also no evidence to support cessation of DOACs in outpatients with COVID‐19 and a prior cardiovascular indication for oral anticoagulation. 18 In a single‐center placebo‐controlled trial, 243 non‐hospitalized, non‐pregnant patients aged 40 and older with COVID‐19 were randomized to oral sulodexide 500 lipase‐releasing units twice daily or placebo.…”

2021 Focused update of the 2017 consensus guidelines of the Asia Pacific Heart Rhythm Society (APHRS) on stroke prevention in atrial fibrillation

“… 307 For patients already treated with NOACs or VKA are infected with COVID‐19 and particularly in case of severe infection requiring hospitalization, patients should ideally continue their anticoagulation rather than discontinue, although outcome data are conflicting. 308 , 309 , 310 , 311…”