key: cord-307745-8dq3vyw9
authors: Rossi, Rosario; Coppi, Francesca; Talarico, Marisa; Boriani, Giuseppe
title: PROTECTIVE ROLE OF CHRONIC TREATMENT WITH DIRECT ORAL ANTICOAGULANTS IN ELDERLY PATIENTS AFFECTED BY INTERSTITIAL PNEUMONIA IN COVID-19 ERA
date: 2020-06-06
journal: Eur J Intern Med
DOI: 10.1016/j.ejim.2020.06.006
sha: 
doc_id: 307745
cord_uid: 8dq3vyw9

• Elderly COVID-19 patients with chronic heart disease have a worse prognosis; • Cardio-active treatment has a protective role in COVID-19 pneumonia; • Anticoagulant chronic assumption in elderly with heart disease reduce mortality.

Since December 2019, coronavirus disease 2019 (COVID-19) caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is an ongoing global health emergency [1] .

Elderly patients affected by chronic heart disease showed a high mortality risk in the setting of COVID-19 interstitial pneumonia [3] . This study aimed to assess if pharmacological cardio-active treatment reduce mortality risk in the setting of COVID-19 interstitial pneumonia.

We retrospectively enrolled elderly patients affected by COVID-19 interstitial pneumonia between February 25, 2020, and April 20, 2020. All the patients were affected by chronic heart disease (CHD) and they were followed in the divisional outpatient clinic of the Cardiology Unit of the Policlinico of Modena Hospital. The follow-up ended on May 5, 2020. The only endpoint of the study was all-cause mortality. This study was approved by the local Ethical Committee (protocol number AOU 0012597) and all the patients gave their consent.

Continuous variables were expressed as mean ± one SD or median (range) values; and categorical data as percentages or proportions. All dichotomous variables were compared for the study outcome utilizing the χ2 test; and continuous variables using analysis of variance or Mann-Whitney U test, as appropriate. Survival probabilities were estimated with the Kaplan-Meier method and survival curves were plotted and compared between groups using the log-rank test. Multivariate Cox regression model was utilized to determine the independent risk factors for mortality. P < 0.05 was statistically significant.

The entire population counted 70 patients, aged > 70 years (median age: 79 years; range: 70-92), with known CHD and a diagnosis of SARS-Cov-2 infection confirmed by nasopharyngeal swab.

The majority of our patients were affected by bilateral (n=58; 82.8%) interstitial pneumonia, confirmed by chest x-ray and/or chest CT images.

During follow-up, 31 patients/70 (44.3%) died. Those who died were older, showed more cardiovascular risk factors (especially hypertension, obesity, and diabetes) and coronary or cerebrovascular disease ( Table 1) . 

Only three parameters increased mortality risk. The strongest was age; then the male gender and the chronic DOAC intake (multivariate analysis reported in Table 2 ). confirmed by epidemiological studies in many countries [5] . Age represents the most powerful independent and prognostic factor in the multivariate analysis. On the contrary, hypertension, obesity, and diabetes were not significant maybe because their prevalence is often age-related. Male gender, which represents a self-determining factor, not depending on age, was significantly associated with mortality risk. The latter finding is a consolidated hallmark in Italy [6] .

It is important to underline that any of the drugs chronically taken for the cardiovascular disease increased mortality risk. Following our assumption, we should not interrupt cardio-active drugs in elderly patients affected by cardiovascular disease and COVID-19.

Most cardio-active drugs did not influence mortality risk. Among these, we underline the neutral role of the renin-angiotensin system inhibitors: angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs), confirmed by several studies [7, 8] .

The most important finding of our study is the demonstrated protective role of anticoagulant drugs.

Chronic DOAC intake is an independent parameter associated with a decreased mortality risk in our population. COVID-19 is mainly treated as a primary pulmonary disease, but according to the available literature, it is a more complex disease. Recent observations suggest a pivotal role of vascular damage (a sort of endothelitis, associated with thrombosis of the small pulmonary vessels) [7] . Therefore, mortality risk would not be conducted to the acute respiratory distress syndrome alone, but also the thrombosis in pulmonary and other district vessels [7, 9] .

According to these findings, anticoagulant treatment with a prophylactic dose of low molecular weight heparin reduced mortality in patients with COVID-19 [10] . In this scenario, the role of DOAC, the most powerful drugs that directly inhibit coagulation factors, is easy to understand. We believe that the importance of DOAC lies in the chronic intake, which is the only one capable of guaranteeing a real defense against thrombosis since the early stages of the disease, even before the onset of symptoms.

Further studies on a larger population of patients, possibly randomized, are needed to confirm the protective role of DOAC in reducing the mortality risk in COVID-19 patients with pre-existing cardiac diseases.

Cardiovascular implications of fatal outcomes of patients with coronavirus disease 2019 (COVID-19)

Pathophysiological characteristics and therapeutic approaches for pulmonary injury and cardiovascular complications of coronavirus disease 2019

Characteristics of and important lessons from the coronavirus disease 2019 (COVID-19) outbreak in China: Summary of a report of 72314 cases from the Chinese Center for Disease Control and Prevention

Presenting Characteristics, Comorbidities, and Outcomes Among 5700 Patients Hospitalized With COVID-19 in the New York City Area

COVID-19 Lombardy ICU Network. Baseline Characteristics and Outcomes of 1591 Patients Infected With SARS-CoV-2 Admitted to ICUs of the Lombardy Region

Endothelial cell infection and endothelitis in COVID-19. The Lancet's website

Cardiovascular disease, drug therapy, and mortality in COVID-19

Incidence of thrombotic complications in critically ill ICU patients with COVID-19

Anticoagulant treatment is associated with decreased mortality in severe coronavirus disease 2019 patients with coagulopathy

☒ The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work