Venous Thromboembolism, Methylprednisolone, and Heparin in COVID-19 Pneumonia

In a recent clinical trial patients with COVID-19 pneumonia receiving mechanical ventilation, the risk for venous thromboembolism (VTE) was greater among patients treated with methylprednisolone for more than 7 days vs those not receiving methylprednisolone, and therapeutic heparin provided no added benefit to the patients receiving methylprednisolone. These findings, recently published in BMC Pulmonary Medicine, were part of an analysis of real-world observational data on COVID-19 (ClinicalTrials.gov identifier: NCT04347993) obtained from the 13 hospitals of Hackensack Meridian Health (HMH) in New Jersey.

The researchers sought to establish the risk for VTE between no methylprednisolone vs methylprednisolone, as well as the relative risks for varying the dose and duration of methylprednisolone. The study also assessed whether there was a synergistic, dose-dependent association between heparin and methylprednisolone that affected 30-day in-hospital survival.

The analysis was based on a propensity score–matched sample of 759 adult patients admitted to HMH hospitals between March and June 2020, with 380 patients in the no-methylprednisolone group and 379 in the methylprednisolone group. Investigators found that the incidence of VTE was 9% among participants treated with methylprednisolone vs 3% among those who did not receive methylprednisolone (relative risk [RR], 2.92; 95% CI, 1.54-5.55; P <.0001). A significant risk was observed for VTE between methylprednisolone treatment for greater than 7 days compared with methylprednisolone treatment for 7 days or less (RR, 5.46; 95% CI, 2.87-10.34; P <.0001). Further, the median D-dimer in participants without VTE and those with VTE was statistically significant (P <.0003).

Overall, among patients treated with prophylactic heparin only, deaths occurred in 14 individuals who received no oxygen support, 11 who received noninvasive oxygen support, and 17 who received invasive oxygen support or mechanical ventilation (P <.0001). Additionally, in participants who received methylprednisolone and prophylactic heparin, deaths occurred in 10 who received no oxygen support, 6 who received noninvasive oxygen support, and 30 who received invasive oxygen support (P <.0001). Moreover, among patients who received methylprednisolone and therapeutic heparin, deaths occurred in 6 who received no oxygen support, 9 who received noninvasive oxygen support, and 30 who received invasive oxygen support or mechanical ventilation (P =.0059). Patients treated with low-dose methylprednisolone and therapeutic heparin had a trend toward a higher risk for mortality compared with those who received prophylactic heparin (hazard ratio, 1.81; 95% CI, 0.994-3.294; P =.0522).

The investigators concluded that “Methylprednisolone for [more than] 7 days had a higher association of venous thromboembolism,” and that “There was no added benefit of therapeutic heparin to methylprednisolone on mechanically ventilated patients.” The findings also suggested that in patients hospitalized with COVID-19 pneumonia, the use of therapeutic heparin should be reserved for those with radiographic evidence of venous thromboembolic disease.

Disclosure: One of the study authors has declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of the author’s disclosures.  

Reference  

Go RC, Nyirenda T, Bojarian M, et al.  Methylprednisolone, venous thromboembolism, and association with heparin to 30 days in hospital survival in severe Covid-19 pneumonia. BMC Pulm Med. 2022;22(1):6. doi:10.1186/s12890-021-01810-1