By Crystal Phend

Anticoagulation for patients hospitalized with COVID-19 was associated with lower risk of death or intubation in an observational study from New York City's pandemic peak.

In-hospital mortality risk was a relative 50% lower with standard prophylactic dosing and 47% lower with higher therapeutic-level dosing after adjustment for other factors, both statistically significant when compared with COVID-19 patients in Mount Sinai hospitals not given an anticoagulant (mortality rates of 21.6%, 28.6%, and 25.6%, respectively).

Intubation was less likely for anticoagulant-treated COVID-19 patients as well (adjusted HR 0.69 with prophylactic dosing, 95% CI 0.51-0.94, and aHR 0.72 with therapeutic dosing, 95% CI 0.58-0.89), reported Anuradha Lala, MD, of the Icahn School of Medicine at Mount Sinai in New York City, and colleagues.

Major bleeding events adjudicated by clinician chart review turned up a "low" rate of 1.7% (33 of 1,959) on prophylactic anticoagulation and 3% (27 of 900) on therapeutic anticoagulation compared with 1.9% (29 of 1,530) on no anticoagulant during hospitalization.

"The study has severe limitations due to its retrospective nature," cautioned Stephan Moll, MD, of the University of North Carolina at Chapel Hill Hemophilia and Thrombosis Center.

"However, NIH prospective studies on inpatient and outpatient [prophylaxis] comparing different anticoagulation management strategies are planned and hopefully starting soon so that we can get beyond all these retrospective studies and data of the last few months, which all have ascertainment bias," he said.

Lala's group had previously reported on their experience with anticoagulation among 2,773 patients treated early in the pandemic, finding an in-hospital survival advantage with therapeutic-dose anticoagulation among mechanically ventilated patients and with longer duration anticoagulation.

A subsequent study had suggested elevated mortality risk with preemptive therapeutic-dose anticoagulation in COVID-19 patients.

The new data included 4,389 adults with laboratory-confirmed SARS-CoV-2 infection admitted from March 1 to April 30, 2020, at the five New York City hospitals in the Mount Sinai system.

The researchers conservatively classified anyone treated for less than 48 hours with an anticoagulant as fitting the control group, unless the drug was stopped due to major bleeding. Patients discharged within 24 hours, as well as those treated with both therapeutic and prophylactic regimens, were excluded.

The study also evaluated the first 26 autopsies on COVID-19 patients in the health system, which turned up thromboembolism in 11 (42%), while it had been suspected pre-mortem in only one. "Our findings are in line with what other studies have shown," Lala said. "We're seeing more clots than we would have ever suspected previously."

All told, 34.9% of the COVID-19 patients didn't receive anticoagulation. These patients might have been treated earlier in the pandemic when practices were changing, said Lala, who pointed to the increasing observational data supporting prophylactic anticoagulation over time. But the predominant factor appeared to be less severe illness, she said.

Even so, there's plenty of data from prior randomized trials supporting pharmacologic thrombotic prophylaxis that makes it the standard of care in-hospital, regardless of COVID-19, argued Behnood Bikdeli, MD, of Brigham and Women's Hospital and Harvard in Boston, who has been involved with COVID-related anticoagulation consensus recommendations and clinical trials.

"Since this study has been completed, thank God New York is not under grips of COVID and we hope that it stays that way. But if I were to consider how to treat a patient if they came to my doorstep now, I would be inclined to use anticoagulation. Nonetheless, I think the dose and the agent need to be confirmed with clinical trials," Lala agreed.

The current study has better explanation of methodology and more confirmatory analyses that make the results more believable than the previous study from the organization, but trials like INSPIRATION and the NIH's ACTIV will be the ones to really provide answers, Bikdeli said.

"The question they are trying to answer is perhaps one of the top three or four important questions we face as clinicians dealing with COVID-19," he said.