Hospitalized patients were treated with therapeutic doses of systemic anticoagulants

The use of anticoagulants in the treatment of hospitalized Covid-19 patients appeared to improve hospital survival times both in and out of the ICU, in an analysis of outcomes among more than 2,700 cases treated within the Mount Sinai Health System in New York City.

Survival among patients requiring mechanical ventilation was more than twice as high in the anticoagulant-treatment group (29.1% mortality versus 62.7% mortality).

And, among patients on mechanical ventilation who did not survive, the median time to death was 21 days among those treated with blood thinners versus 9 days among those not receiving anticoagulant therapies, and bleeding events were not significantly different among the two groups (3.0% in the anticoagulant group versus 1.9%).

The observational study findings were published online May 6 in the Journal of the American College of Cardiology, and the Mount Sinai researchers are planning a larger study involving 5,000 patients to help clarify the relative impact of oral antithrombotics, subcutaneous heparin, and intravenous heparin on outcomes among patients with Covid-19.

“We are excited about these preliminary results that may have a positive impact on Covid-19 patients and potentially give them a greater chance of survival, although more studies are needed,” said senior researcher Girish Nadkarni, MD, in a written press statement.

In an interview with BreakingMED, researcher Valentin Fuster, MD, said anticoagulants should be considered when patients are admitted to the ER and test positive for Covid-19, unless patients have an elevated risk for bleeding.

Stephan Moll, MD, of the University of North Carolina School of Medicine, Chapel Hill, noted in an email exchange with BreakingMED that the observed mortality benefit among the sickest patients treated with anticoagulants (AC) is in keeping with those of a recently published study involving 449 patients. However, another study involving 184 Covid-19 patients receiving treatment in ICUs failed to show a survival advantage associated with anticoagulation.

“Thus, promising as these data from a large patient population are, the issue still has discrepant published data,” Moll noted. “However, they support the general impression by a number of clinicians and academicians, me included, that a somewhat more aggressive anticoagulation strategy in Covid-19 patients may be warranted.”

Moll noted that hospitalized coronavirus patients are at increased risk for thrombosis, with pulmonary embolisms (PEs) occurring in roughly 1-in-4 patients in ICUs and that PEs and deep vein thrombosis (DVTs) often occur despite standard-dose anticoagulation.

Moll and colleagues recently published an anticoagulation algorithm for patients with Covid-19, which calls for aggressive anticoagulation for all hospitalized patients, unless clear bleeding contraindications are present.

Moll said there is still considerable debate regarding appropriate anticoagulant dosing in patients hospitalized for Covid-19.

“Some are aggressive with anticoagulation based on a number of preliminary data suggesting failure of standard anticoagulation and possible benefit of full-dose anticoagulation in at least the very such patients, such as ICU patients, and high D-dimer patients,” he said. “Others say one should stick to solid established evidence and use routine VTE prophylaxis as in non-Covid patients, and full dose only when there is an established indication, such as DVT or PE.”

He said the strategy adopted at UNC Medical Center involves an intermediate anticoagulation intensity approach coupled with reviewing new publications and adjusting the algorithm to newly release data.

The Mount Sinai study included 2,773 patients with laboratory-confirmed Covid-19 treated between March 14 and April 11.

Researchers used a Cox proportional hazards model to assess the efficacy of treatment-dose systemic anticoagulation (including oral, subcutaneous and intravenous forms) on hospital mortality, adjusting for age, sex, ethnicity, BMI, history or hypertension, heart failure, Afib, type 2 diabetes, anticoagulant history and admission date.

A total of 786 patients (28%) were treated with systemic AC during their hospital stay, and the median hospitalization duration was 5 days.

Median time from admission to AC initiation was 2 days, and median (IQR) duration of AC treatment was 3 days (2-7 days).

In-hospital mortality among patients treated with AC was 22.5% with a median survival of 21 days, compared to 22.8% among patients not receiving AC (median survival time, 14 days).

“Overall, we observed significantly increased baseline prothrombin time, activated partial thromboplastin time, lactate dehydrogenase, ferritin, C reactive protein and D-dimer values among individuals who received in-hospital AC as compared to those who did not,” the researchers wrote, adding that the differences were not seen among patients who required mechanical ventilation (n=395).

Multivariate proportional hazards modeling showed longer duration of AC treatment to be associated with a reduced mortality risk (adjusted HR, 0.86 per day, 95% CI, 0.82-0.89; P<0.001).

Of the 24 AC -treated patients who experienced bleeding events, 15 (63% had bleeding events after starting AC and 9 (37%) had bleeding events before starting the therapy.

“Although limited by its observational nature, unobserved confounding, unknown indication for AC, lack of metrics to further classify illness severity in the mechanically ventilated subgroup, and indication bias, our findings suggest that systemic AC may be associated with improved outcomes among patients hospitalized with Covid-19,” the researchers concluded. “The potential benefits of systemic AC, however, need to be weighed against the risk of bleeding and therefore should be individualized.”

  1. The use of anticoagulants in the treatment of hospitalized Covid-19 patients appeared to improve hospital survival times both in and outside the ICU, in an analysis of outcomes among more than 2,700 cases.

  2. Survival among patients requiring mechanical ventilation was more than twice as high in the anticoagulant-treatment group (29.1% mortality versus 62.7% mortality).

Salynn Boyles, Contributing Writer, BreakingMED™

This research was funded by the NIH’s National Center for Advancing Translational Sciences.

Researcher Girish Nadkarini reported receiving consulting and advisory board participation fees from RenalytixAI. Dr. Nadkarini also reported owning equity in RenalytixAI and being a scientific co-founder of the company and Pensieve Health, receiving operational funding from Goldfinch Bio and consulting fees from BioVie Inc., AstraZeneca, Reaata and others. Researcher Zahi A. Fayad disclosed consulting fees from Alexion and GlaxoSmithKline, owning equity and financial compensation as a board member and advisor for Trained Therapeutix Discovery and researcher funding from Daiichi Sankyo, Amgen, Bristol Myers Squibb and others.

Cat ID: 125

Topic ID: 79,125,791,932,570,574,125,190,520,926,192,927,151,928,925,934