Effect of heparin treatment on pulmonary embolism and in-hospital death in unvaccinated COVID-19 patients without overt deep vein thrombosis.
Anticoagulant
D-dimer
Multi-state model
Retrospective study
Survival analysis
Journal
Thrombosis journal
ISSN: 1477-9560
Titre abrégé: Thromb J
Pays: England
ID NLM: 101170542
Informations de publication
Date de publication:
20 Jun 2022
20 Jun 2022
Historique:
received:
19
02
2022
accepted:
09
06
2022
entrez:
20
6
2022
pubmed:
21
6
2022
medline:
21
6
2022
Statut:
epublish
Résumé
Pulmonary embolism (PE) without overt deep vein thrombosis (DVT) was common in hospitalized coronavirus-induced disease (COVID)-19 patients and represented a diagnostic, prognostic, and therapeutic challenge. The aim of this study was to analyze the prognostic role of PE on mortality and the preventive effect of heparin on PE and mortality in unvaccinated COVID-19 patients without overt DVT. Data from 401 unvaccinated patients (age 68 ± 13 years, 33% females) consecutively admitted to the intensive care unit or the medical ward were included in a retrospective longitudinal study. PE was documented by computed tomography scan and DVT by compressive venous ultrasound. The effect of PE diagnosis and any heparin use on in-hospital death (primary outcome) was analyzed by a classical survival model. The preventive effect of heparin on either PE diagnosis or in-hospital death (secondary outcome) was analyzed by a multi-state model after having reclassified patients who started heparin after PE diagnosis as not treated. Median follow-up time was 8 days (range 1-40 days). PE cumulative incidence and in-hospital mortality were 27% and 20%, respectively. PE was predicted by increased D-dimer levels and COVID-19 severity. Independent predictors of in-hospital death were age (hazards ratio (HR) 1.05, 95% confidence interval (CI) 1.03-1.08, p < 0.001), body mass index (HR 0.93, 95% CI 0.89-0.98, p = 0.004), COVID-19 severity (severe versus mild/moderate HR 3.67, 95% CI 1.30-10.4, p = 0.014, critical versus mild/moderate HR 12.1, 95% CI 4.57-32.2, p < 0.001), active neoplasia (HR 2.58, 95% CI 1.48-4.50, p < 0.001), chronic obstructive pulmonary disease (HR 2.47; 95% CI 1.15-5.27, p = 0.020), respiratory rate (HR 1.06, 95% CI 1.02-1.11, p = 0.008), heart rate (HR 1.03, 95% CI 1.01-1.04, p < 0.001), and any heparin treatment (HR 0.35, 95% CI 0.18-0.67, p = 0.001). In the multi-state model, preventive heparin at prophylactic or intermediate/therapeutic dose, compared with no treatment, reduced PE risk and in-hospital death, but it did not influence mortality of patients with a PE diagnosis. PE was common during the first waves pandemic in unvaccinated patients, but it was not a negative prognostic factor for in-hospital death. Heparin treatment at any dose prevented mortality independently of PE diagnosis, D-dimer levels, and disease severity.
Sections du résumé
BACKGROUND
BACKGROUND
Pulmonary embolism (PE) without overt deep vein thrombosis (DVT) was common in hospitalized coronavirus-induced disease (COVID)-19 patients and represented a diagnostic, prognostic, and therapeutic challenge. The aim of this study was to analyze the prognostic role of PE on mortality and the preventive effect of heparin on PE and mortality in unvaccinated COVID-19 patients without overt DVT.
METHODS
METHODS
Data from 401 unvaccinated patients (age 68 ± 13 years, 33% females) consecutively admitted to the intensive care unit or the medical ward were included in a retrospective longitudinal study. PE was documented by computed tomography scan and DVT by compressive venous ultrasound. The effect of PE diagnosis and any heparin use on in-hospital death (primary outcome) was analyzed by a classical survival model. The preventive effect of heparin on either PE diagnosis or in-hospital death (secondary outcome) was analyzed by a multi-state model after having reclassified patients who started heparin after PE diagnosis as not treated.
RESULTS
RESULTS
Median follow-up time was 8 days (range 1-40 days). PE cumulative incidence and in-hospital mortality were 27% and 20%, respectively. PE was predicted by increased D-dimer levels and COVID-19 severity. Independent predictors of in-hospital death were age (hazards ratio (HR) 1.05, 95% confidence interval (CI) 1.03-1.08, p < 0.001), body mass index (HR 0.93, 95% CI 0.89-0.98, p = 0.004), COVID-19 severity (severe versus mild/moderate HR 3.67, 95% CI 1.30-10.4, p = 0.014, critical versus mild/moderate HR 12.1, 95% CI 4.57-32.2, p < 0.001), active neoplasia (HR 2.58, 95% CI 1.48-4.50, p < 0.001), chronic obstructive pulmonary disease (HR 2.47; 95% CI 1.15-5.27, p = 0.020), respiratory rate (HR 1.06, 95% CI 1.02-1.11, p = 0.008), heart rate (HR 1.03, 95% CI 1.01-1.04, p < 0.001), and any heparin treatment (HR 0.35, 95% CI 0.18-0.67, p = 0.001). In the multi-state model, preventive heparin at prophylactic or intermediate/therapeutic dose, compared with no treatment, reduced PE risk and in-hospital death, but it did not influence mortality of patients with a PE diagnosis.
CONCLUSIONS
CONCLUSIONS
PE was common during the first waves pandemic in unvaccinated patients, but it was not a negative prognostic factor for in-hospital death. Heparin treatment at any dose prevented mortality independently of PE diagnosis, D-dimer levels, and disease severity.
Identifiants
pubmed: 35725464
doi: 10.1186/s12959-022-00393-z
pii: 10.1186/s12959-022-00393-z
pmc: PMC9207168
doi:
Types de publication
Journal Article
Langues
eng
Pagination
34Informations de copyright
© 2022. The Author(s).
Références
Cardiovasc Revasc Med. 2021 Oct;31:34-40
pubmed: 33257254
PLoS One. 2020 Aug 25;15(8):e0238216
pubmed: 32841275
Am J Physiol Lung Cell Mol Physiol. 2020 Aug 1;319(2):L277-L288
pubmed: 32551862
N Engl J Med. 2021 Aug 26;385(9):790-802
pubmed: 34351721
J Thromb Haemost. 2020 Jul;18(7):1743-1746
pubmed: 32320517
J Thromb Haemost. 2020 Oct;18(10):2629-2635
pubmed: 32692874
Ann Intern Med. 2007 Oct 16;147(8):573-7
pubmed: 17938396
J Thromb Haemost. 2020 Sep;18(9):2103-2109
pubmed: 32558075
N Engl J Med. 2021 Aug 26;385(9):777-789
pubmed: 34351722
Chest. 2021 Oct;160(4):1471-1480
pubmed: 34153340
Thromb Haemost. 2020 Aug;120(8):1230-1232
pubmed: 32349132
Eur Heart J Qual Care Clin Outcomes. 2021 Jul 21;7(4):330-339
pubmed: 34107535
J Thromb Haemost. 2020 Aug;18(8):1859-1865
pubmed: 32459046
Mayo Clin Proc. 2021 Mar;96(3):518-520
pubmed: 33673900
Crit Care. 2020 Jul 27;24(1):464
pubmed: 32718343
Cochrane Database Syst Rev. 2022 Mar 4;3:CD013739
pubmed: 35244208
Lancet. 2020 Mar 28;395(10229):1054-1062
pubmed: 32171076
Inflamm Res. 2020 Dec;69(12):1181-1189
pubmed: 32918567
N Engl J Med. 2020 Jul 9;383(2):120-128
pubmed: 32437596
Ann Intern Med. 2020 Sep 1;173(5):350-361
pubmed: 32422076
J Thromb Haemost. 2020 Apr;18(4):844-847
pubmed: 32073213
Front Cardiovasc Med. 2020 Aug 06;7:151
pubmed: 32850990
Thromb Res. 2020 Sep;193:86-89
pubmed: 32531548
Ann Vasc Surg. 2020 Oct;68:83-87
pubmed: 32673648
Ann Intern Med. 2006 Aug 15;145(4):247-54
pubmed: 16908915
Chest. 2022 Jul;162(1):213-225
pubmed: 35167861
Respir Med Res. 2020 Nov;78:100789
pubmed: 33022510
JAMA Intern Med. 2021 Dec 1;181(12):1612-1620
pubmed: 34617959
Stat Med. 2007 May 20;26(11):2389-430
pubmed: 17031868
Stat Med. 1992 Jul;11(10):1273-87
pubmed: 1518991
Lancet Haematol. 2020 Jun;7(6):e438-e440
pubmed: 32407672
J Thromb Haemost. 2020 May;18(5):1094-1099
pubmed: 32220112
J Thromb Thrombolysis. 2020 Aug;50(2):287-291
pubmed: 32445064
J Thromb Thrombolysis. 2021 May;51(4):978-984
pubmed: 33386559
Eur Respir J. 2021 Jul 20;58(1):
pubmed: 33692122
Radiology. 2021 Feb;298(2):E70-E80
pubmed: 33320063
Int J Lab Hematol. 2021 Dec 16;:
pubmed: 34914184
Circulation. 2020 Jul 14;142(2):184-186
pubmed: 32330083
Respir Med. 2020 Aug;169:106023
pubmed: 32454268