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      Impact of oral anticoagulation on clinical outcomes of COVID-19: a nationwide cohort study of hospitalized patients in Germany

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          Abstract

          Objectives

          The aim of this study was to investigate the impact of concomitant long-term medication—with a focus on ACE inhibitors and oral anticoagulation—on clinical outcomes in patients hospitalized with coronavirus disease 2019.

          Methods

          This is a retrospective cohort study using claims data of the biggest German health insurance company AOK, covering 26.9 million people all over Germany. In particular, patient-related characteristics and co-medication were evaluated. A multivariable logistic regression model was adopted to identify independent predictors for the primary outcome measure of all-cause mortality or need for invasive or non-invasive ventilation or extracorporeal membrane oxygenation.

          Results

          6637 patients in 853 German hospitals were included. The primary outcome occurred in 1826 patients (27.5%). 1372 patients (20.7%) died, 886 patients (13.3%) needed respiratory support, and 53 patients (0.8%) received extracorporeal membrane oxygenation. 34 of these patients survived (64.2%). The multivariable model demonstrated that pre-existing oral anticoagulation therapy with either vitamin-K antagonists OR 0.57 (95% CI 0.40–0.83, p = 0.003) or direct oral anticoagulants OR 0.71 (95% CI 0.56–0.91, p = 0.007) —but not with antiplatelet therapy alone OR 1.10 (95% CI 0.88–1.23, p = 0.66)—was associated with a lower event rate. This finding was confirmed in a propensity match analysis.

          Conclusions

          In a multivariable analysis, a therapy with both direct oral anticoagulants or vitamin-K antagonists—but not with antiplatelet therapy—was associated with improved clinical outcomes. ACE inhibitors did not impact outcomes. Prospective randomized trials are needed to verify this hypothesis.

          Graphic abstract

          Supplementary Information

          The online version contains supplementary material available at 10.1007/s00392-020-01783-x.

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          Most cited references19

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          Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China

          Chaolin Huang, Yeming Wang, Xingwang Li … (2020)
          Summary Background A recent cluster of pneumonia cases in Wuhan, China, was caused by a novel betacoronavirus, the 2019 novel coronavirus (2019-nCoV). We report the epidemiological, clinical, laboratory, and radiological characteristics and treatment and clinical outcomes of these patients. Methods All patients with suspected 2019-nCoV were admitted to a designated hospital in Wuhan. We prospectively collected and analysed data on patients with laboratory-confirmed 2019-nCoV infection by real-time RT-PCR and next-generation sequencing. Data were obtained with standardised data collection forms shared by WHO and the International Severe Acute Respiratory and Emerging Infection Consortium from electronic medical records. Researchers also directly communicated with patients or their families to ascertain epidemiological and symptom data. Outcomes were also compared between patients who had been admitted to the intensive care unit (ICU) and those who had not. Findings By Jan 2, 2020, 41 admitted hospital patients had been identified as having laboratory-confirmed 2019-nCoV infection. Most of the infected patients were men (30 [73%] of 41); less than half had underlying diseases (13 [32%]), including diabetes (eight [20%]), hypertension (six [15%]), and cardiovascular disease (six [15%]). Median age was 49·0 years (IQR 41·0–58·0). 27 (66%) of 41 patients had been exposed to Huanan seafood market. One family cluster was found. Common symptoms at onset of illness were fever (40 [98%] of 41 patients), cough (31 [76%]), and myalgia or fatigue (18 [44%]); less common symptoms were sputum production (11 [28%] of 39), headache (three [8%] of 38), haemoptysis (two [5%] of 39), and diarrhoea (one [3%] of 38). Dyspnoea developed in 22 (55%) of 40 patients (median time from illness onset to dyspnoea 8·0 days [IQR 5·0–13·0]). 26 (63%) of 41 patients had lymphopenia. All 41 patients had pneumonia with abnormal findings on chest CT. Complications included acute respiratory distress syndrome (12 [29%]), RNAaemia (six [15%]), acute cardiac injury (five [12%]) and secondary infection (four [10%]). 13 (32%) patients were admitted to an ICU and six (15%) died. Compared with non-ICU patients, ICU patients had higher plasma levels of IL2, IL7, IL10, GSCF, IP10, MCP1, MIP1A, and TNFα. Interpretation The 2019-nCoV infection caused clusters of severe respiratory illness similar to severe acute respiratory syndrome coronavirus and was associated with ICU admission and high mortality. Major gaps in our knowledge of the origin, epidemiology, duration of human transmission, and clinical spectrum of disease need fulfilment by future studies. Funding Ministry of Science and Technology, Chinese Academy of Medical Sciences, National Natural Science Foundation of China, and Beijing Municipal Science and Technology Commission.
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            Clinical Characteristics of Coronavirus Disease 2019 in China

            Wei-jie Guan, Zheng-yi Ni, Yu Hu … (2020)
            Abstract Background Since December 2019, when coronavirus disease 2019 (Covid-19) emerged in Wuhan city and rapidly spread throughout China, data have been needed on the clinical characteristics of the affected patients. Methods We extracted data regarding 1099 patients with laboratory-confirmed Covid-19 from 552 hospitals in 30 provinces, autonomous regions, and municipalities in mainland China through January 29, 2020. The primary composite end point was admission to an intensive care unit (ICU), the use of mechanical ventilation, or death. Results The median age of the patients was 47 years; 41.9% of the patients were female. The primary composite end point occurred in 67 patients (6.1%), including 5.0% who were admitted to the ICU, 2.3% who underwent invasive mechanical ventilation, and 1.4% who died. Only 1.9% of the patients had a history of direct contact with wildlife. Among nonresidents of Wuhan, 72.3% had contact with residents of Wuhan, including 31.3% who had visited the city. The most common symptoms were fever (43.8% on admission and 88.7% during hospitalization) and cough (67.8%). Diarrhea was uncommon (3.8%). The median incubation period was 4 days (interquartile range, 2 to 7). On admission, ground-glass opacity was the most common radiologic finding on chest computed tomography (CT) (56.4%). No radiographic or CT abnormality was found in 157 of 877 patients (17.9%) with nonsevere disease and in 5 of 173 patients (2.9%) with severe disease. Lymphocytopenia was present in 83.2% of the patients on admission. Conclusions During the first 2 months of the current outbreak, Covid-19 spread rapidly throughout China and caused varying degrees of illness. Patients often presented without fever, and many did not have abnormal radiologic findings. (Funded by the National Health Commission of China and others.)
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              Presenting Characteristics, Comorbidities, and Outcomes Among 5700 Patients Hospitalized With COVID-19 in the New York City Area

              Safiya Richardson, Jamie Hirsch, Mangala Narasimhan … (2020)
              There is limited information describing the presenting characteristics and outcomes of US patients requiring hospitalization for coronavirus disease 2019 (COVID-19).
              Article 0 comments Cited 4643 times – based on 0 reviews     Review now
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                Author and article information

                Contributors
                Georg M. Fröhlich:
                ORCID: http://orcid.org/0000-0001-5059-3770
                georg.froehlich@charite.de
                Journal
                Journal ID (nlm-ta): Clin Res Cardiol
                Journal ID (iso-abbrev): Clin Res Cardiol
                Title: Clinical Research in Cardiology
                Publisher: Springer Berlin Heidelberg (Berlin/Heidelberg )
                ISSN (Print): 1861-0684
                ISSN (Electronic): 1861-0692
                Publication date (Electronic): 8 January 2021
                Pages: 1-10
                Affiliations
                [1 ]GRID grid.6363.0, ISNI 0000 0001 2218 4662, Department of Cardiology, , Charité–Universitätsmedizin Berlin, ; Campus Benjamin Franklin, Hindenburgdamm 30, 12203 Berlin, Germany
                [2 ]AOK Research Institute (WIdO), Berlin, Germany
                [3 ]GRID grid.9647.c, ISNI 0000 0004 7669 9786, Heart Center Leipzig at University of Leipzig and Leipzig Heart Institute, ; Leipzig, Germany
                [4 ]GRID grid.412282.f, ISNI 0000 0001 1091 2917, School of Medicine, , University Hospital Dresden, ; Dresden, Germany
                [5 ]GRID grid.472754.7, ISNI 0000 0001 0695 783X, Deutsches Herzzentrum München, ; Munich, Germany
                [6 ]GRID grid.452396.f, ISNI 0000 0004 5937 5237, DZHK Partner Site Berlin, ; Berlin, Germany
                [7 ]GRID grid.484013.a, Berlin Institute of Health (BIH), ; Anna-Louisa-Karsch-Straße 2, 10178 Berlin, Germany
                Author information
                http://orcid.org/0000-0001-5059-3770
                Article
                Publisher ID: 1783
                DOI: 10.1007/s00392-020-01783-x
                PMC ID: 7791911
                PubMed ID: 33416918
                SO-VID: bd435177-28a5-42cc-ba62-1bfb47d69071
                Copyright © © Springer-Verlag GmbH Germany, part of Springer Nature 2021
                License:

                This article is made available via the PMC Open Access Subset for unrestricted research re-use and secondary analysis in any form or by any means with acknowledgement of the original source. These permissions are granted for the duration of the World Health Organization (WHO) declaration of COVID-19 as a global pandemic.

                History
                Date received : 15 September 2020
                Date accepted : 18 November 2020
                Categories
                Subject: Original Paper

                ScienceOpen disciplines: Cardiovascular Medicine
                Keywords: covid-19,doacs,vitamin-k-antagonist,antiplatelet therapy,ace inhibitors,ecmo
                Data availability:
                ScienceOpen disciplines: Cardiovascular Medicine
                Keywords: covid-19, doacs, vitamin-k-antagonist, antiplatelet therapy, ace inhibitors, ecmo

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