Anticoagulants May Aid COVID-19 Patients, NYC Data Suggest

Systemic anticoagulation is linked to better survival among patients hospitalized with COVID-19, suggest new data from New York City. The benefit, most evident in those on ventilators, did not come at the cost of increased bleeding. 

Investigator Valentin Fuster, MD, PhD (Icahn School of Medicine at Mount Sinai, New York, NY), emphasized to TCTMD that the observational study will be followed by larger, more rigorous analyses. Still, it’s an important step in an ongoing project, he added.

Early on, physicians in the Mount Sinai Health System tried out anticoagulation in a few patients with the idea that the “disease might have a thrombotic component,” he explained. “It was just no more than a try. After 3,000 patients, we had the intuitive feeling that those on anticoagulants [did better].”

Around the same time, the literature began to suggest that COVID-19 has dramatic prothrombotic effects in some individuals. So, from mid-March onward, anticoagulation became standard at Mount Sinai for all COVID-19 patients unless contraindicated, Fuster said. “We developed a guideline.”

Early Signs Positive

In this report, published online Thursday in the Journal of the American College of Cardiology, Fuster and colleagues document in-hospital mortality for the 2,773 patients admitted to the Mount Sinai hospitals with laboratory-confirmed COVID-19 between March 14 and April 11, 2020.

During hospitalization, 786 (28%) of these patients received systemic anticoagulation (oral, subcutaneous, or IV), with a median time from admission to therapy initiation of 2 days and median treatment duration of 3 days.

For those given anticoagulation, in-hospital mortality was 22.5% and, among those who died, the median survival was 21 days. For the those who didn’t receive anticoagulation, the figures were 22.8% and 14 days, respectively.

Patients in the anticoagulation group were more likely to later require mechanical ventilation (29.8% vs 8.1%; P < 0.001). They also tended to have increased baseline prothrombin time, longer activated partial thromboplastin time, and higher levels of lactate dehydrogenase, ferritin, C-reactive protein, and D-dimer; but when restricting analysis to the subset of 395 patients who received ventilation, those differences disappeared.

Among those on mechanical ventilation, in-hospital mortality was 29.1% and median survival was 21 days among anticoagulant-treated patients; by comparison, the death rate was 62.7% and median survival was 9 days among the patients who didn’t receive these drugs.

Using a Cox multivariate proportional hazards model adjusting for age, sex, ethnicity, body mass index (BMI), history of hypertension, heart failure, atrial fibrillation, prior anticoagulant use, and admission date, the researchers found that longer time on anticoagulation was linked to lower mortality risk (adjusted HR 0.86 per day; 95% 0.82-0.89).

Rates of major bleeding (hemoglobin < 7 g/dL and any red blood cell [RBC] transfusion, ≥ 2 units of RBC transfusion ≤ 48 hours, or a diagnosis code for major bleeding) were similar no matter whether patients did or didn’t receive anticoagulation (3.0% vs 1.9%; P = 0.2). For those on anticoagulation, 37% of the bleeding events occurred before drug initiation. Bleeding was more common in patients who were intubated than in those who were not (7.5% vs 1.35%).

As of 4 days ago, based on these results, Mount Sinai physicians follow a new guideline that emphasizes anticoagulants for all—with some exceptions such as people with a history of bleeding or low platelet count—given at an even higher dose than used in the current paper, Fuster told TCTMD. “Why? Because there was no difference in bleeding in terms of those who received anticoagulation versus those who didn’t.” The exact strategy depends on various factors such as whether patients are in the intensive care unit, have high BMI, or develop renal failure.

On this backdrop of wider use of anticoagulation, the researchers are now looking at 5,000 patients in the Mount Sinai system to validate their initial results. Analyses will assess not only mortality but also details on anticoagulant type, dosing, and other nuances, Fuster said, predicting results will be available in about 4 weeks.

Following this, he said, studies will prospectively examine how best to treat three groups: hospitalized patients, patients discharged from the hospital, and people with relatively benign forms of COVID-19 who present to the hospital without being admitted.

For Fuster, the current report inherently is limited due to its observational nature. Still, “it opens the door,” he said.