Anticoagulation Therapy in Patients With Coronavirus Disease 2019

Results From a Multicenter International Prospective Registry (Health Outcome Predictive Evaluation for Corona Virus Disease 2019 (HOPE-COVID19))

Francesco Santoro, MD, PhD; Ivan J. Núñez-Gil, MD, PhD; María C. Viana-Llamas, MD; Charbel Maroun Eid, MD; Rodolfo Romero, MD; Inmaculada Fernández Rozas, MD; Alvaro Aparisi, MD; Victor Manuel Becerra-Muñoz, MD; Marcos García Aguado, MD; Jia Huang, MD; Ludovica Maltese, MD; Enrico Cerrato, MD; Emilio Alfonso-Rodriguez, MD; Alex Fernando Castro Mejía, MD; Francisco Marin, MD; Sergio Raposeiras Roubin, MD; Martino Pepe, MD; Victor H. Moreno Munguia, MD; Gisela Feltes, MD; Jesus Varas Navas, MD; Bernardo Cortese, MD; Luis Buzón, MD; Cristoph Liebetrau, MD; Raquel Ramos-Martinez, MD; Antonio Fernandez-Ortiz, MD; Vicente Estrada, MD; Natale Daniele Brunetti, MD, PhD

Disclosures

Crit Care Med. 2021;49(6):e624-e633.

Conclusions

Anticoagulation therapy in general population with COVID-19 was not associated with better survival rates but with higher bleeding risk. Better results in term of lower mortality through use of anticoagulation therapy were observed in patients admitted with respiratory failure requiring invasive ventilation.

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Table 1. Baseline Clinical Features of Overall Coronavirus Disease 2019 Population and of Patients That Received Anticoagulation Therapy and Not
Variables	General Population	Anticoagulation Therapy, Mean ± SD	No Anticoagulation Therapy, Mean ± SD	p
Number of patients, n (	5,838	2,601 (44)	3,214 (56)
Age, yr	65 ± 16	66 ± 15	63 ± 27	0.01
Male sex, %	59	60	58	0.02
Clinical baseline profile, %
Hypertension	49	53	46	0.36
Diabetes	19	21	17	0.01
Obesity (body mass index > 30)	22	24	21	0.01
Renal insufficiency (creatinine clearance < 30 mL/min)	6	7	6	0.01
History of lung disease	19	21	17	0.01
History of heart disease	23	26	21	0.01
History of cancer	14	14	14	0.92
Clinical features at admission, %
Asymptomatic	5	3	6	0.01
Hyposmia/anosmia	7	7	7	0.55
Dysgeusia	7	8	7	0,34
Diarrhea	19	20	19	0.76
Laboratory data
Procalcitonin above normal values, %	22	22	22	0.08
Admission d-dimer levels > 3 normal values, %	62	72	59	0.01
Admission creatinine levels (mg/dL)	1.19 ± 0.59	1.22 ± 0.60	1.16 ± 0.57	0.65
Admission leucocytes count (×10⁹/L)	7,148 ± 3,891	7,321 ± 3,825	7,001 ± 3,918	0.59
Admission lymphocyte (×10⁹/L)	1,320 ± 1,811	1,210 ± 1,511	1,414 ± 2,030	0.01
Admission platelets count (×10⁹/L)	213 ± 96	216 ± 93	211 ± 93	0.01

Table 2. Multivariable Cox' Regression Analysis in Subjects Admitted With Respiratory Failure (Nonanticoagulated Before Admission)
Variable	Risk Ratio (95% Lower–Upper)	p
Anticoagulant therapy	0.58 (0.49–0.67)	< 0.001
Age	1.05 (1.05–1.06)	< 0.001
Male	1.25 (1.06–1.48)	0.0075
ICU admission	0.93 (0.65–1.32)	0.6779
Hypertension	1.08 (0.87–1.34)	0.4881
Diabetes	1.06 (0.89–1.27)	0.4853
Obesity	1.30 (1.09–1.56)	0.0030
Renal failure	1.48 (1.19–1.83)	0.0004
Any lung disease	0.86 (0.71–1.03)	0.1062
Atrial fibrillation	1.45 (0.98–2.16)	0.0651
Any heart disease	1.26 (1.04–1.52)	0.0201
Any cancer	1.15 (0.94–1.40)	0.1736
Angiotensin-converting enzyme inhibitors/angiotensin receptor blockers	0.97 (0.80–1.17)	0.7590
β-blockers	0.93 (0.76–1.14)	0.4909
Noninvasive ventilation	1.16 (0.96–1.40)	0.1216
Invasive ventilation	2.68 (1.88–3.83)	< 0.001

Authors and Disclosures

Francesco Santoro, MD, PhD¹, Ivan J. Núñez-Gil, MD, PhD², María C. Viana-Llamas, MD³, Charbel Maroun Eid, MD⁴, Rodolfo Romero, MD⁵, Inmaculada Fernández Rozas, MD⁶, Alvaro Aparisi, MD⁷, Victor Manuel Becerra-Muñoz, MD⁸, Marcos García Aguado, MD⁹, Jia Huang, MD¹⁰, Ludovica Maltese, MD¹¹, Enrico Cerrato, MD¹², Emilio Alfonso-Rodriguez, MD¹³, Alex Fernando Castro Mejía, MD¹⁴, Francisco Marin, MD¹⁵, Sergio Raposeiras Roubin, MD¹⁶, Martino Pepe, MD¹⁷, Victor H. Moreno Munguia, MD², Gisela Feltes, MD¹⁸, Jesus Varas Navas, MD¹⁹, Bernardo Cortese, MD²⁰, Luis Buzón, MD²¹, Cristoph Liebetrau, MD²², Raquel Ramos-Martinez, MD²³, Antonio Fernandez-Ortiz, MD², Vicente Estrada, MD² and Natale Daniele Brunetti, MD, PhD¹

1 Department of Medical and Surgical Sciences, University of Foggia, Foggia, Italy.
2 Hospital Clinico San Carlos, Madrid, Spain.
3 Hospital Universitario Guadalajara, Guadalajara, Spain.
4 Hospital Universitario La Paz Instituto de Investigacion, Hospital Universitario La Paz (IdiPAZ), Madrid, Spain.
5 Hospital Universitario Getafe, Madrid, Spain.
6 Hospital Universitario Severo Ochoa, Leganés, Spain.
7 Hospital Clinico Universitario de Valladolid, Valladolid, Spain.
8 Hospital Clinico Universitario Virgen de la Victoria, Malaga, Spain.
9 Hospital Puerta de Hierro de Majadahonda, Majadahonda, Madrid, Spain.
10 The Second Affiliated Hospital of Southern University of Science and Technology, Shenzhen, China.
11 Sant'Andrea Hospital, Vercelli, Italy.
12 San Luigi Gonzaga University Hospital, Orbassano and Rivoli Infermi Hospital, Rivoli, Italy.
13 Institute of Cardiology and Cardiovascular Surgery, Havana, Cuba.
14 Hospital General del norte de Guayaquil IESS, Los Ceibos, Guayaquil, Ecuador.
15 Hospital de la Arreixaca, Murcia, Spain.
16 University Hospital Alvaro Cunqueiro, Vigo, Spain.
17 University Hospital of Bari, Bari, Italy.
18 Nuestra Señora de América, Madrid, Spain.
19 Hospital Universitario Infanta Sofia, San Sebastian de los Reyes, Madrid, Spain.
20 San Carlo Clinic, Milano, Italy.
21 Hospital Universitario, Burgos, Spain.
22 Kerckhoff Heart and Thorax Center, Bad Nauheim, Germany.
23 Hospital General de Albacete, Albacete, Spain.

Drs. Santoro and Núñez-Gil contributed equally and should be both considered as first authors.

Drs. Romero and García Aguado received support for article research from the National Institutes of Health. Dr. Moreno Munguia received support for article research from Instituto de Investigación Sanitaria del Hospital Clínico San Carlos. The remaining authors have disclosed that they do not have any potential conflicts of interest.