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

Abstract

Introduction: A hypercoagulable condition was described in patients with 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 hospitalised in 30 clinical centres in Italy from February 19, 2020 to May 23, 2020 with laboratory-confirmed SARS-CoV-2 infection, were analysed. The primary end-point 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 (HR=0.60; 95%CI: 0.49 to 0.74; E-value=2.04). This association was particularly evident in patients with a higher severity of disease or strong coagulation activation. Conclusions: In-hospital heparin treatment was associated with lower mortality, particularly in severely ill COVID-19 patients and in those with strong coagulation activation. The results from randomised clinical trials are eagerly awaited to provide clear-cut recommendations.

Venous Thromboembolism in Patients Discharged after COVID-19 Hospitalization

“…Therefore, it is not routinely recommended. 25 However, because of the high incidence of thrombotic complications in hospitalized patients with COVID-19 and the potential benefits of heparin on outcome in such patients, 12,15,16,19 it is unclear whether thromboprophylaxis should be routinely provided after COVID-19 hospitalization. With the ongoing pandemic, data to evaluate the risk and benefit of thromboprophylaxis in this particular COVID-19 population are urgently needed.…”

“…[2][3][4][5][6][7][8][9][10][11] Furthermore, more extensive activation of the coagulation system has been associated with worse clinical outcomes, so that LMWH administration at intermediate or therapeutic doses has been suggested to improve outcome in patients hospitalized with COVID-19. [12][13][14][15][16][17] Therefore, many studies have focused on identifying the optimal dose of LMWH for in-hospital thromboprophylaxis. 11,[17][18][19][20] In contrast, limited data are available on incidence of symptomatic and subclinical VTE after COVID-19 hospitalization, as systematic screening for VTE in the outpatient setting can be cumbersome.…”

Protective effect of oral anticoagulant drugs in atrial fibrillation patients admitted for COVID-19: Results from the CORIST study

“…In this study, however, mortality rates were much higher in the two groups of patients on anticoagulant or antiplatelet treatment than in controls, suggesting that the populations compared may have been different from those compared in our study limited to AF patients with and without anticoagulation. Protective effect on mortality was also reported with the use of heparin, mainly at prophylactic doses, in the CORIST study [8]. In this retrospective observational study, 70% COVID-19 patients received heparin during hospitalization and had a 40% lower risk of mortality compared to patients not treated with heparin [8].…”

“…Protective effect on mortality was also reported with the use of heparin, mainly at prophylactic doses, in the CORIST study [8]. In this retrospective observational study, 70% COVID-19 patients received heparin during hospitalization and had a 40% lower risk of mortality compared to patients not treated with heparin [8]. Thus, the issue on whether anticoagulation should be administered at prophylactic or therapeutic doses remains open.…”

Back to the future with machine learning

“…Thousands of existing drugs have already been studied in in vitro and in vivo models of COVID-19, 400+ drugs have been administered to COVID-19 patients, and dozens of drugs have undergone randomized controlled trials 1,2 . Several existing treatments, including dexamethasone, tocilizumab and heparin are likely to have contributed to major reductions in mortality among critically ill patients with COVID-19 by limiting immune hyper-activation and mitigating clotting-related sequelae of the virus [3][4][5] . Relatively less success has been found with antivirals that could be effective earlier in the disease course at preventing COVID-19 morbidity and mortality.…”