Role of Low-Molecular-Weight Heparin in Hospitalized Patients With Severe Acute Respiratory Syndrome Coronavirus 2 Pneumonia: A Prospective Observational Study

Abstract

Background: This study was conducted to evaluate the impact of low-molecular-weight heparin (LMWH) on the outcome of patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pneumonia.

Methods: This is a prospective observational study including consecutive patients with laboratory-confirmed SARS-CoV-2 pneumonia admitted to the University Hospital of Pisa (March 4-April 30, 2020). Demographic, clinical, and outcome data were collected. The primary endpoint was 30-day mortality. The secondary endpoint was a composite of death or severe acute respiratory distress syndrome (ARDS). Low-molecular-weight heparin, hydroxychloroquine, doxycycline, macrolides, antiretrovirals, remdesivir, baricitinib, tocilizumab, and steroids were evaluated as treatment exposures of interest. First, a Cox regression analysis, in which treatments were introduced as time-dependent variables, was performed to evaluate the association of exposures and outcomes. Then, a time-dependent propensity score (PS) was calculated and a PS matching was performed for each treatment variable.

Results: Among 315 patients with SARS-CoV-2 pneumonia, 70 (22.2%) died during hospital stay. The composite endpoint was achieved by 114 (36.2%) patients. Overall, 244 (77.5%) patients received LMWH, 238 (75.5%) received hydroxychloroquine, 201 (63.8%) received proteases inhibitors, 150 (47.6%) received doxycycline, 141 (44.8%) received steroids, 42 (13.3%) received macrolides, 40 (12.7%) received baricitinib, 13 (4.1%) received tocilizumab, and 13 (4.1%) received remdesivir. At multivariate analysis, LMWH was associated with a reduced risk of 30-day mortality (hazard ratio [HR], 0.36; 95% confidence interval [CI], 0.21-0.6; P < .001) and composite endpoint (HR, 0.61; 95% CI, 0.39-0.95; P = .029). The PS-matched cohort of 55 couples confirmed the same results for both primary and secondary endpoint.

Conclusions: This study suggests that LMWH might reduce the risk of in-hospital mortality and severe ARDS in coronavirus disease 2019. Randomized controlled trials are warranted to confirm these preliminary findings.

Keywords: ARDS; COVID-19; SARS-CoV-2; low-molecular weight; mortality.

Figure 1.

Impact of Different Treatments on the Risk of All-Cause Mortality (Primary Endpoint) and a Composite of Mortality or Severe ARDS (Composite Endpoint) in PS-Matched Patients With SARS-CoV-2 Pneumonia. Abbreviations: ARDS, acute respiratory distress syndrome; CI, confidence interval; HR, hazard ratio; LMWH, low-molecular-weight heparin; PS, propensity score; SARS-CoV-2, severe acute respiratory syndrome coronavirus 2; hsTnT, high-sensitivity troponin T (ng/L). NOTE: PS matched includes the following: age, male sex, Charlson comorbidity index, severity of illness at hospital admission assessed by Sequential Organ Failure Assessment (SOFA) score, lymphocytes, platelets count, and hsTnT values during the first 48 hours after admission, PiO2/FiO2 on admission, all medications (including LMWH, doxycycline, macrolides, proteases inhibitors, hydroxychloroquine, steroids, baricitinib, tocilizumab, and remdesivir), excluding the current treatment of interest.