Heparin in COVID-19 Patients Is Associated with Reduced In-Hospital Mortality: the Multicenter Italian CORIST Study *

被引：89

作者：

Di Castelnuovo, Augusto ^{[1
]}

Costanzo, Simona ^{[2
]}

Antinori, Andrea ^{[3
]}

Berselli, Nausicaa ^{[4
]}

Blandi, Lorenzo ^{[5
]}

Bonaccio, Marialaura ^{[2
]}

Cauda, Roberto ^{[6
,7
]}

Guaraldi, Giovanni ^{[8
]}

Menicanti, Lorenzo ^{[9
]}

Mennuni, Marco ^{[10
]}

Parruti, Giustino ^{[11
]}

Patti, Giuseppe ^{[10
]}

Santilli, Francesca ^{[12
,13
]}

Signorelli, Carlo ^{[14
]}

Vergori, Alessandra ^{[15
]}

Abete, Pasquale ^{[16
]}

Ageno, Walter ^{[17
]}

Agodi, Antonella ^{[18
,19
]}

Agostoni, Piergiuseppe ^{[20
,21
]}

Aiello, Luca ^{[22
]}

Al Moghazi, Samir ^{[23
]}

Arboretti, Rosa ^{[24
]}

Astuto, Marinella ^{[25
]}

Aucella, Filippo ^{[26
]}

Barbieri, Greta ^{[27
]}

Bartoloni, Alessandro ^{[28
,29
]}

Bonfanti, Paolo ^{[30
,31
]}

Cacciatore, Francesco ^{[16
]}

Caiano, Lucia ^{[17
]}

Carrozzi, Laura ^{[32
,33
]}

Cascio, Antonio ^{[34
]}

Ciccullo, Arturo ^{[6
]}

Cingolani, Antonella ^{[6
,7
]}

Cipollone, Francesco ^{[12
,13
]}

Colomba, Claudia ^{[34
]}

Colombo, Crizia ^{[10
]}

Crosta, Francesca ^{[11
]}

Danzi, Gian Battista ^{[35
]}

D'Ardes, Damiano ^{[12
,13
]}

Donati, Katleen De Gaetano ^{[6
]}

Di Gennaro, Francesco ^{[36
]}

Di Tano, Giuseppe ^{[35
]}

D'Offizi, Gianpiero ^{[37
]}

Fantoni, Massimo ^{[6
,7
]}

Fusco, Francesco Maria ^{[38
]}

Gentile, Ivan ^{[39
]}

Gianfagna, Francesco ^{[1
,17
]}

Grandone, Elvira ^{[26
]}

Graziani, Emauele ^{[40
]}

Grisafi, Leonardo ^{[10
]}

机构：

[1] Mediterranea Cardioctr, Naples, Italy

[2] IRCCS Neuromed, Dept Epidemiol & Prevent, Via Elettron, I-86077 Pozzilli, Isernia, Italy

[3] IRCCS, Natl Inst Infect Dis L Spallanzani, UOC Immunodeficienze Virali, Rome, Italy

[4] Univ Modena & Reggio Emilia, Sect Publ Hlth, Dept Biomed Metab & Neural Sci, Modena, Italy

[5] Univ Pavia, Pavia, Italy

[6] Fdn Policlin Univ A Gemelli IRCCS, Rome, Italy

[7] Univ Cattolica Sacro Cuore, Dipartimento Sicurezza & Bioet Sede Roma, Rome, Italy

[8] Univ Modena & Reggio Emilia, Dept Surg Med Dent & Morphol Sci, Infect Dis Unit, Modena, Italy

[9] IRCCS Policlin San Donato, Milan, MI, Italy

[10] Univ Piemonte Orientale, Maggiore Carita Hosp, Novara, Italy

[11] Azienda Sanitaria Locale AUSL Pescara, Dept Infect Dis, Pescara, Italy

[12] SS Annunziata Hosp, Clin Med, Dept Med & Aging, Chieti, Italy

[13] Univ G dAnnunzio, Chieti, Italy

[14] Univ Vita Salute San Raffaele, Sch Med, Milan, Italy

[15] Natl Inst Infect Dis Lazzaro Spallanzani IRCCS, Dept HIV AIDS, Rome, Italy

[16] Univ Napoli Federico II, Dipartimento Sci Med Traslaz, Naples, Italy

[17] Univ Insubria, Dept Med & Surg, Varese, Italy

[18] Univ Catania, Dept Med & Surg Sci & Adv Technol GF Ingrassia, Catania, Italy

[19] AOU Policlin G Rodol San Marco, Catania, Italy

[20] Ctr Cardiol Monzino IRCCS, Milan, Italy

[21] Univ Milan, Dept Clin Sci & Community Hlth, Sect Cardiovasc, Milan, Italy

[22] Gen Osped Morgagni Pierantoni, Anestesia & Rianimaz, Dipartimento Chirurg, UOC, Forli, Italy

[23] IRCCS, Natl Inst Infect Dis L Spallanzani, UOC Infezioni Sistemiche Immunodepresso, Rome, Italy

[24] Univ Padua, Dept Civil Environm & Architectural Engn, Padua, Italy

[25] Univ Catania, AOU Policlin G Rodol San Marco, Dept Gen Surg & Med Surg Specialties, UO Anestesia,Rianimaz 1,PO G Rodol, Catania, Italy

[26] Fdn IRCCS Casa Sollievo Sofferenza, Foggia, Italy

[27] Univ Pisa, Azienda Osped Univ Pisana, Dept Surg, Med & Mol Med & Crit Care, Pisa, Italy

[28] Univ Florence, Dept Expt & Clin Med, Florence, Italy

[29] Azienda Osped Univ Careggi, Florence, Italy

[30] Osped San Gerardo, ASSTMonza, UOCMalattie Infett, Monza, Italy

[31] Univ Milano Bicocca, Sch Med & Surg, Milan, Italy

[32] Azienda Osped Univ Pisana, Cardiovasc & Thorac Dept, Pisa, Italy

[33] Univ Pisa, Pisa, Italy

[34] Univ Palermo, Infect & Trop Dis Unit, Dept Hlth Promot Mother & Child Care, Internal Med & Med Specialties PROMISE, Palermo, Italy

[35] Osped Cremona, Dept Cardiol, Cremona, Italy

[36] IRCCS Neuromed, Med Direct, Pozzilli, Isernia, Italy

[37] IRCCS, Natl Inst Infect Dis L Spallanzani, UOC Malattie Infett Epatol, Rome, Italy

[38] Osped Cotugno, Azienda Osped Colli, UOC Infezioni Sistemiche & Immunodepresso, Naples, Italy

[39] Univ Naples Federico II, Dept Clin Med & Surg, Naples, Italy

[40] Osped Ravenna, Med Interna, AUSL Romagna, Ravenna, Italy

[41] Univ Padua, Dept Cardiol Thorac & Vasc Sci, Div Resp Pathophysiol, Padua, Italy

[42] EE Osped Reg F Miulli, COVID 19 Unit, Acquaviva Fonti, Bari, Italy

[43] PO San Giuseppe Moscati, UOC Pneumol, Taranto, Italy

[44] Osped Edoardo Bassini Cinisello Balsamo, ASST Milano Nord, Milan, Italy

[45] Presidio Osped S Maria Loreto Nuovo, ASL Napoli Ctr 1, UOC Med, Naples, Italy

[46] PO Santissima Trinita Cagliari, Cagliari, Italy

[47] Magna Graecia Univ Catanzaro, Infect & Trop Dis Unit, Dept Med & Surg Sci, Catanzaro, Italy

[48] Univ Pisa, Azienda Osped Univ Pisana, Dept Clin & Expt Med, Pisa, Italy

[49] Univ Pisa, Dipartimento Farm, Pisa, Italy

[50] AOU Policlin G Rodol San Marco, UOC Malattie Infett & Tropicali, PO San Marco, Catania, Italy

来源：

THROMBOSIS AND HAEMOSTASIS | 2021年 / 121卷 / 08期

关键词：

COVID-19; coronavirus; heparin; coagulation activation; treatments; mortality; MANAGEMENT;

D O I：

10.1055/a-1347-6070

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

Introduction A hypercoagulable condition was described in patients with coronavirus disease 2019 (COVID-19) and proposed as a possible pathogenic mechanism contributing to disease progression and lethality. Aim We evaluated if in-hospital administration of heparin improved survival in a large cohort of Italian COVID-19 patients. Methods In a retrospective observational study, 2,574 unselected patients hospitalized in 30 clinical centers in Italy from February 19, 2020 to June 5, 2020 with laboratory-confirmed severe acute respiratory syndrome coronavirus-2 infection were analyzed. The primary endpoint in a time-to event analysis was in-hospital death, comparing patients who received heparin (low-molecular-weight heparin [LMWH] or unfractionated heparin [UFH]) with patients who did not. We used multivariable Cox proportional-hazards regression models with inverse probability for treatment weighting by propensity scores. Results Out of 2,574 COVID-19 patients, 70.1% received heparin. LMWH was largely the most used formulation (99.5%). Death rates for patients receiving heparin or not were 7.4 and 14.0 per 1,000 person-days, respectively. After adjustment for propensity scores, we found a 40% lower risk of death in patients receiving heparin (hazard ratio=0.60; 95% confidence interval: 0.49-0.74; E-value=2.04). This association was particularly evident in patients with a higher severity of disease or strong coagulation activation. Conclusion In-hospital heparin treatment was associated with a lower mortality, particularly in severely ill COVID-19 patients and in those with strong coagulation activation. The results from randomized clinical trials are eagerly awaited to provide clear-cut recommendations.

引用

页码：1054 / 1065

页数：12

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