Prior use of therapeutic anticoagulation does not protect against COVID‐19 related clinical outcomes in hospitalized patients: A propensity score‐matched cohort study

Spiegelenberg, Janneke; Gelder, Marleen M.H.J. van; Maas, Martje L.; Hovens, Marcel M.C.; Esselink, Anne C.; Dofferhoff, Anton S M; Janssen, Rob; Maat, Josephine van de; Janssen, Nico; Blaauw, Marc; Hassing, Robert Jan; Apeldoorn, Marjan van; Kerckhoffs, Angèle P. M.; Veerman, Karin; Hoogerwerf, Jacobien J.; Kramers, Cornelis; Leentjens, Jenneke

doi:10.1111/bcp.14877

Cited by 23 publications

(26 citation statements)

References 29 publications

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“…Hence, the role of prior OAC therapy in the context of COVID-19 is gaining interest. For example, a recent study concluded that prior use of therapeutic anticoagulation was not associated with improved survival in hospitalized COVID-19 patients [ 39 ]. Similarly, a small study found that regular VKA use in hospitalized frail older patients with COVID-19 was associated with increased mortality during the first week [ 40 ].…”

Section: Discussionmentioning

confidence: 99%

Efficacy and safety of direct-acting oral anticoagulants compared to vitamin K antagonists in COVID-19 outpatients with cardiometabolic diseases

Rivera‐Caravaca

Harrison

Buckley

et al. 2021

Cardiovasc Diabetol

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Background It remains uncertain if prior use of oral anticoagulants (OACs) in COVID-19 outpatients with multimorbidity impacts prognosis, especially if cardiometabolic diseases are present. Clinical outcomes 30-days after COVID-19 diagnosis were compared between outpatients with cardiometabolic disease receiving vitamin K antagonist (VKA) or direct-acting OAC (DOAC) therapy at time of COVID-19 diagnosis. Methods A study was conducted using TriNetX, a global federated health research network. Adult outpatients with cardiometabolic disease (i.e. diabetes mellitus and any disease of the circulatory system) treated with VKAs or DOACs at time of COVID-19 diagnosis between 20-Jan-2020 and 15-Feb-2021 were included. Propensity score matching (PSM) was used to balance cohorts receiving VKAs and DOACs. The primary outcomes were all-cause mortality, intensive care unit (ICU) admission/mechanical ventilation (MV) necessity, intracranial haemorrhage (ICH)/gastrointestinal bleeding, and the composite of any arterial or venous thrombotic event(s) at 30-days after COVID-19 diagnosis. Results 2275 patients were included. After PSM, 1270 patients remained in the study (635 on VKAs; 635 on DOACs). VKA-treated patients had similar risks and 30-day event-free survival than patients on DOACs regarding all-cause mortality, ICU admission/MV necessity, and ICH/gastrointestinal bleeding. The risk of any arterial or venous thrombotic event was 43% higher in the VKA cohort (hazard ratio 1.43, 95% confidence interval 1.03–1.98; Log-Rank test p = 0.029). Conclusion In COVID-19 outpatients with cardiometabolic diseases, prior use of DOAC therapy compared to VKA therapy at the time of COVID-19 diagnosis demonstrated lower risk of arterial or venous thrombotic outcomes, without increasing the risk of bleeding.

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Section: Discussionmentioning

confidence: 99%

Efficacy and safety of direct-acting oral anticoagulants compared to vitamin K antagonists in COVID-19 outpatients with cardiometabolic diseases

Rivera‐Caravaca

Harrison

Buckley

et al. 2021

Cardiovasc Diabetol

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“…Seven studies 4,5,9,10,12-14 focusing on prehospital use of anticoagulants and one study 29 focusing on therapeutic use of anticoagulants found no difference in risk of mortality, mechanical ventilation or acute distress respiratory syndrome. Notably, some were of small sample size 4,[12][13][14] , with unclear exposure definition 5 , classifying patients who initiated therapeutic anticoagulation on day 3 or later after ICU admission in the control group 29 or used composite outcomes 9,10 , limiting the interpretation of the results. Two cohort studies showed a higher risk of admission to ICU, intubation, or death associated with anticoagulants in patients with COVID-19 disease, compared with non-use, but the results were possibly due to confounding by indication.…”

Section: Findings In Contextmentioning

confidence: 99%

“…[1][2][3] While anticoagulants appear to be a useful treatment option for hospitalised patients with COVID-19, most studies investigated the potential protective role of routine use of oral anticoagulants (OACs) in COVID-19 related outcomes were of small sample size or in hospital setting only. [4][5][6][7][8][9][10][11][12][13][14] Notably, people taking oral anticoagulants are likely to have more comorbidities than those not, and so comparing COVID-19 outcomes for OAC use with no use could be subject to confounding. Importantly, use of OAC treatment is partly threshold based; according to the guidelines for the management of patients with atrial fibrillation (AF), which is also one of the Quality and Outcome Framework indicators a payment incentive scheme in English general practice.…”

Section: Introductionmentioning

confidence: 99%

Association between oral anticoagulants and COVID-19 related outcomes: two cohort studies

Tomlinson

Brown

et al. 2021

Preprint

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ObjectivesWe investigated the role of routinely prescribed oral anticoagulants (OACs) in COVID-19 outcomes, comparing current OAC use versus non-use in Study 1; and warfarin versus direct oral anticoagulants (DOACs) in Study 2.DesignTwo cohort studies, on behalf of NHS England.SettingPrimary care data and pseudonymously-linked SARS-CoV-2 antigen testing data, hospital admissions, and death records from England.ParticipantsStudy 1: 70,464 people with atrial fibrillation (AF) and CHA□DS□-VASc score of 2. Study 2: 372,746 people with non-valvular AF.Main outcome measuresTime to test for SARS-CoV-2, testing positive for SARS-CoV-2, COVID-19 related hospital admission, COVID-19 deaths or non-COVID-19 deaths in Cox regression.ResultsIn Study 1, we included 52,416 current OAC users and 18,048 non-users. We observed no difference in risk of being tested for SARS-CoV-2 associated with current use (adjusted HR, 1.01, 95%CI, 0.96 to 1.05) versus non-use. We observed a lower risk of testing positive for SARS-CoV-2 (adjusted HR, 0.73, 95%CI, 0.60 to 0.90), and COVID-19 deaths (adjusted HR, 0.69, 95%CI, 0.49 to 0.97) associated with current use versus non-use. In Study 2, we included 92,339 warfarin users and 280,407 DOAC users. We observed a lower risk of COVID-19 deaths (adjusted HR, 0.79, 95%CI, 0.76 to 0.83) associated with warfarin versus DOACs. Similar associations were found for all other outcomes.ConclusionsAmong people with AF and a CHA□DS□-VASc score of 2, those receiving OACs had a lower risk of receiving a positive COVID-19 test and severe COVID-19 outcomes than non-users; this might be explained by a causal effect of OACs in preventing severe COVID-19 outcomes or more cautious behaviours leading to reduced infection risk. There was no evidence of a higher risk of severe COVID-19 outcomes associated with warfarin versus DOACs in people with non-valvular AF regardless of CHA□DS□-VASc score.Key pointsWhat is already known on this topicCurrent studies suggest that prophylactic or therapeutic anticoagulant use, particularly low molecular weight heparin, lower the risk of pulmonary embolism and mortality during hospitalisation among patients with COVID-19.Reduced vitamin K status has been reported to be correlated with severity of COVID-19. This could mean that warfarin, as a vitamin K antagonist, is associated with more severe COVID-19 disease than non-vitamin K anticoagulants.What this study addsIn 70,464 people with atrial fibrillation, at the threshold of being treated with an OAC based on risk of stroke, we observed a lower risk of testing positive for SARS-CoV-2 and COVID-19 related deaths associated with routinely prescribed OACs, relative to non-use.This might be explained by OACs preventing severe COVID-19 outcomes, or more cautious behaviours and environmental factors reducing the risk of SARS-CoV-2 infection in those taking OACs.In 372,746 people with non-valvular atrial fibrillation, there was no evidence of a higher risk of severe COVID-19 outcomes associated with warfarin compared with DOACs.

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“…However, it soon became clear that patients continued to have thrombotic events on prophylactic heparin (Trimaille et al, 2020) and some studies suggested that using intermediate dose heparin was more effective (Stessel et al, 2020;Meizlish et al, 2021a) although other studies showed no benefit from the increased dose of heparin (Investigators, 2021). One study found that therapeutic anticoagulation in COVID-19 patients reduced the risk of pulmonary embolism but had no effect on mortality (Spiegelenberg et al, 2021). This is reminiscent of bacterial sepsis where anti-coagulants such as activated protein C and heparin provided some benefit but never really resolved the issue.…”

Section: Covid-19 and Thrombosismentioning

confidence: 99%

Targeting SARS-CoV-2-Platelet Interactions in COVID-19 and Vaccine-Related Thrombosis

Cox

2021

Front. Pharmacol.

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It is clear that COVID-19 is more than a pneumonia and is associated with a coagulopathy and multi-organ failure. While the use of anti-coagulants does reduce the incidence of pulmonary emboli, it does not help with survival. This suggests that the coagulopathy is more likely to be platelet-driven rather than thrombin-driven. There is significant evidence to suggest that SARS-CoV-2 virions directly interact with platelets to trigger activation leading to thrombocytopenia and thrombosis. I propose a model of multiple interactions between SARS-CoV-2 and platelets that has many similarities to that with Staphylococcus aureus and Dengue virus. As platelet activation and thrombosis are major factors in poor prognosis, therapeutics that target the platelet-SARS-CoV-2 interaction have potential in treating COVID-19 and other virus infections.

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Prior use of therapeutic anticoagulation does not protect against COVID‐19 related clinical outcomes in hospitalized patients: A propensity score‐matched cohort study

Cited by 23 publications

References 29 publications

Efficacy and safety of direct-acting oral anticoagulants compared to vitamin K antagonists in COVID-19 outpatients with cardiometabolic diseases

Efficacy and safety of direct-acting oral anticoagulants compared to vitamin K antagonists in COVID-19 outpatients with cardiometabolic diseases

Association between oral anticoagulants and COVID-19 related outcomes: two cohort studies

Targeting SARS-CoV-2-Platelet Interactions in COVID-19 and Vaccine-Related Thrombosis

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