We analyzed the thromboembolic and fatal outcomes in a COVID-19 cohort (n = 35,484 patients), comparing those individuals who were exposed to OAC to those non-exposed, matched by age and sex. In our study, those patients exposed to OAC had a higher risk of hospital admission (OR 1.30, 95% CI 1.22–1.38) and thromboembolic events – stroke and pulmonary embolism (OR 2.5, 95% CI 2.04–3.06) – than those who were not treated with OAC. Those patients exposed to OAC had a lower risk of mortality than non-exposed (OR 0.88, CI 95% 0.83–0.93). We found no differences in the risk of pneumonia between groups. Similar results were found when we excluded the population living in nursing homes, which had a higher rate of COVID-19 infection and negative outcomes during the first wave of the pandemic when compared with the general population.23
Patients with cardiovascular conditions have been reported as having a higher risk for adverse events from COVID-19 and thrombotic events.4–7 For instance, Inciardi et al. analyzed data of 99 COVID-19 patients with pneumonia, 53.5% of them had previous cardiovascular diseases, and found a higher mortality in this subgroup of patients (RR 2.35, 95% CI 1.08–5.09). They did not report on the use of comedications.25
As anticoagulant therapy as LMWH is used to treat thrombotic complications in COVID-19 patients, chronic treatment with OAC may play a role in lowering the risk of thrombotic events caused by SARS-CoV-2 infection, and in this alignment, some studies have previously assessed complications in COVID-19 patients according to their previous exposure to OAC, finding different results. Rivera-Caravaca et al. studied 1,002 patients from Ecuador, Germany, Italy and Spain who were admitted to hospital due to COVID-19 and were previously treated with OAC. They found a HR of 1.53 (CI95% 1.08–2.16) for mortality when compared OAC users with non-users.26
Russo et al. enrolled 192 COVID-19 patients to study the risk of suffering acute respiratory distress syndrome (ARDS) and/or death during hospitalization. They found no protective effect for these events in the 26 (13.5%) patients who were OAC users admitted to hospital.27
Denas et al. conducted a population-based propensity score-matched study in the Veneto Region, Italy. They included 4,697 COVID-19 patients older than 65 and matched 559 anticoagulated patients to 559 non-exposed. They found a rate ratio of all-cause mortality higher in non-anticoagulated patients (32.2% vs 26.5%), although the estimate was not statistically significant; HR 0.81, 95%CI 0.65–1.01. The authors discussed a possible role of OAC in reducing the mortality in that group of patients, although taking into account that they might have been switched to LMWH during hospitalization and other interventions might have also affected the outcomes.28 Similar results, finding OAC exposure as having a protecting role, are shown in an Italian study [HR for death 0.38 (0.17–0.58)].29 Our findings do not show a higher risk among those exposed to OAC, risk that also do not show when analyzing a subpopulation of those patients not in long-term facilities.
Tremblay et al. conducted a study in 3,772 COVID-19 patients treated with OAC, antiplatelets or non-treated with antithrombotics. They did two propensity score matchings, comparing OAC-treated vs non-treated and antiplatelets-treated vs non-treated. The HR for all-cause mortality, mechanical ventilation and hospital admission were not significant. The Kaplan-Meyer survival analyses did not show differences between groups. They did not exclude the possibility that anticoagulation during COVID-19 infection may be useful but they did not find that previous treatment with OAC may protect from severe forms of COVID-19.30
In a study in France, 90% of COVID-19 patients admitted to the ICU because of pulmonary thromboembolism were receiving prophylactic anticoagulant (LMWH) treatment according to critically ill patients’ guidelines, but the study did not analyze if these patients were already on prophylactic anticoagulant treatment due to previously indications such as atrial fibrillation.31
We found that OAC users were more frequently hospitalized than non-users. This outcome has not been assessed in the cited studies above, as all patients included in those studies were already hospitalized for SARS-CoV-2 infection.15,16,31,32 Our study includes those hospitalized and those who not, and it reveals that anticoagulated patients had more comorbidities and were older, well known risks for hospitalization being confirmed with our results.
Among the limitations of our study there is the reliability of the COVID-19 diagnoses; we included patients without a confirmed result as during the first wave of the pandemic in our setting PCR test were not always performed. This limitation has been described in other research as during the beginning of the pandemic diagnosis test for COVID-19 were not widely available, and clinical algorithms have been used to assess COVID-19 diagnosis.33 Another limitation is the lack of hospital information: we cannot capture ICU admission, ventilation or treatments administered during the admission, which clearly have influence in the prognosis and outcomes of COVID-19.
We also found in our study that OAC exposure was not associated to an increased risk in the mortality rate, although we cannot assess the effect of the interventions applied during hospital admission on the mortality, scales of prognosis, complications, treatments and specific outcomes in COVID-19 hospital admitted patients, as our database is a PHC database and does only record the dates of admission and diagnoses and cause of discharge.
Some strengths of our study include the large number of patients included, representativeness for general population, and complete socio-demographic data. We must highlight that our cohort are PHC patients, so we have estimated the risk of death and hospitalization for a different population from the only hospitalized ones that are usually studied.