August 26, 2020
Mount Sinai Study Demonstrates Efficacy of Anticoagulants for COVID-19 Patients
August 26, 2020—The Mount Sinai Hospital and Icahn School of Medicine at Mount Sinai in New York, New York, announced the publication of findings from an observational study that showed that all regimens of anticoagulants were far superior to no anticoagulants in COVID-19 patients. More specifically, patients on both a therapeutic full dose and those on a prophylactic lower dose showed approximately a 50% higher chance of survival and approximately a 30% lower chance of intubation than patients not on anticoagulants.
“Anticoagulation, Mortality, Bleeding and Pathology Among Patients Hospitalized with COVID-19: A Single Health System Study” by Girish N. Nadkarni, MD, et al was accepted for publication and is available online in Journal of the American College of Cardiology (JACC). Dr. Nadkarni is Cofounder and Codirector of the Mount Sinai COVID Informatics Center and Clinical Director of the Hasso Plattner Institute for Digital Health at Mount Sinai.
The work was prompted by the discovery that many patients hospitalized with COVID-19 developed high levels of life-threatening blood clots.
On May 6, Mount Sinai announced the publication of a research letter from the investigators of the Mount Sinai COVID Informatics Center. The letter reported that treating hospitalized COVID-19 patients with anticoagulants may improve their chances of survival. The announcement stated that the study could provide new insight on how to treat and manage coronavirus patients once they are admitted to the hospital.
The May 6 research letter by Ishan Paranjpe, BS, et al was published in JACC (2020;76:122-124). It is included in the JACC COVID-19 Clinical Guidance for Global Cardiovascular Clinicians, a compendium of recently accepted manuscripts that the editors of the JACC journals hope will best inform health care clinicians’ decision-making.
According to Mount Sinai, those findings from early in the COVID-19 pandemic were among the first to show that anticoagulation therapy was associated with improved survival among hospitalized COVID-19 patients both in and out of the intensive care. But many questions remained—about the size of the potential benefit and about what dosage of this therapy might be more effective.
Now, the investigators of the newly published observational study have suggested some possible answers.
In this study, the investigators looked at six different anticoagulant regimens, including both oral and intravenous dosing, within both therapeutic and prophylactic groups. They observed that therapeutic and prophylactic subcutaneous low-molecular-weight heparin and therapeutic oral apixaban may lead to better results.
Valentin Fuster, MD, Director of Mount Sinai Heart and Physician-in-Chief of The Mount Sinai Hospital, is the senior corresponding author and lead investigator of both the research letter and the observational study. Dr. Fuster is also Editor-in-Chief of JACC.
“This work from the Mount Sinai COVID Informatics Center provides additional insight on the role of anticoagulation in the management of patients admitted to the hospital with COVID-19,” commented Dr. Fuster in the Mount Sinai press release. “Although this is an observational study, it helped in the design of a large-scale international clinical trial that we are coordinating. The randomized trial focuses on those three antithrombotic regimens—therapeutic and prophylactic subcutaneous low-molecular-weight heparin and therapeutic oral apixaban.”
As summarized in the Mount Sinai announcement, the team of investigators evaluated electronic medical records of 4,389 confirmed COVID-19–positive patients admitted to five hospitals in the Mount Sinai Health System in New York City (The Mount Sinai Hospital, Mount Sinai West, Mount Sinai Morningside, Mount Sinai Queens, and Mount Sinai Brooklyn) between March 1 and April 30, 2020.
They specifically looked at survival and death rates for patients placed on therapeutic and prophylactic doses of anticoagulants (oral antithrombotics, subcutaneous heparin, and intravenous heparin) versus those not placed on anticoagulants.
Hazard score was used to estimate risk of death, which took relevant risk factors into account before evaluating the effectiveness of anticoagulation, including age, ethnicity, pre-existing conditions, and whether the patient was already on anticoagulants. The investigators also corrected for disease severity, including low oxygen saturation levels and intubation.
Of the patients analyzed, 900 (20.5%) received a full-treatment dose of anticoagulants. Another 1,959 patients (44.6%) received a lower prophylactic dose of anticoagulants, and 1,530 (34.5%) were not given anticoagulants.
There was a strong association between anticoagulants and reduced likelihood of in-hospital deaths: both therapeutic and prophylactic doses of anticoagulants reduced mortality by approximately 50% compared with patients on no anticoagulants.
Overall, 467 (10.6%) of the patients required intubation and mechanical ventilation during their hospitalization. Those patients on therapeutic anticoagulants had 31% fewer intubations than those not on anticoagulants. Those on prophylactic anticoagulants had 28% fewer intubations.
Additionally, bleeding rates were surprisingly low overall among all patients (≤ 3%), but slightly higher in the therapeutic group compared to the prophylactic and no anticoagulant groups. These findings suggest that clinicians should evaluate patients on an individual basis given the benefit-risk tradeoff, advised the investigators.
Separately, the Mount Sinai investigators looked at autopsy results of 26 COVID-19 patients and found that 11 (42%) had blood clots—pulmonary, brain, and/or heart—that were never suspected in the clinical setting. These findings suggest that treating patients with anticoagulants may be associated with improved survival.
Study investigator Anu Lala, MD, Assistant Professor of Medicine (Cardiology) and Director of Heart Failure Research at the Icahn School of Medicine at Mount Sinai, commented in the Mount Sinai press release, “This report is much more in-depth than our previous brief report and includes many more patients, longer follow-up, and rigorous methodology. Clearly, anticoagulation is associated with improved outcomes, and bleeding rates appear to be low. As a clinician who has treated COVID-19 patients on the front lines, I recognize the importance of having answers as to what the best treatment for these patients entails, and these results will inform the design of clinical trials to ultimately give concrete information.”
Dr. Nadkarni stated, “These observational analyses were done with the highest level of statistical rigor and provide exciting insights into the association of anticoagulation with critical in-hospital outcomes of mortality and intubation. We are excited that results from this observational study in one of the largest and most diverse hospitalized populations have led to an ongoing trial of type, duration, and doses of anticoagulation. Ultimately, we hope this work will lead to improved outcomes and treatment for COVID-19 patients.”
Investigator Zahi Fayad, PhD, added, “This work highlights the need to better understand the disease from a diagnostic and therapeutic point of view and the importance of conducting properly designed diagnostic and interventional studies.” Dr. Fayad is Cofounder of the Mount Sinai COVID Informatics Center and Director of Mount Sinai’s BioMedical Engineering and Imaging Institute.