April 07, 2021
By Douglas L. Jennings, PharmD, FACC, FAHA, FCCP, FHFSA, BCPS
Volume 2, Issue 1
“Searching for INSPIRATION in all the wrong places.”
When trying to talk your way out of a “sticky” situation, nothing helps more than being equipped with the latest and greatest evidence. Unfortunately, when it comes to anticoagulation in patients admitted to hospital with severe infection related to the SARS-CoV-2 virus, nothing is clear, and the evidence is extremely limited. In this week’s issue of Talking Therapeutics, we examine the latest study surrounding the murky subject of anticoagulating patients with severe COVID-19 infection, and what it means for frontline pharmacists practicing in the hospital setting.
Point 1: “Less is More”
Much ado about nothing is perhaps the flavor of this week’s nicely done paper—the INSPIRATION trial—which was published in JAMA. The initial flurry of “we must do something” mentality in the early days of the pandemic spurred many institutions to adopt aggressive anticoagulation protocols aimed at combating the perceived pro-coagulable component of COVID-19 infection. The hypercoagulable state—which was diagnosed largely on laboratory data such as elevate D-dimer levels—prompted many clinicians to start patients on intermediate or full-intensity regimens of heparin and low-molecular weight heparins.
The INPIRATATION trial put this hypothesis to the test by randomizing patients admitted to the ICU with Covid-19 infection to either Intermediate-dose (enoxaparin, 1 mg/kg daily, n = 276) or standard prophylactic anticoagulation (enoxaparin, 40 mg daily, n = 286). This study—which was conducted in 10 academic centers in Iran—found that the primary composite outcome venous or arterial thrombosis, treatment with extracorporeal membrane oxygenation, or mortality within 30 days was nearly identical between the two groups. Furthermore, while rates of major bleeding and severe thrombocytopenia were low in the overall cohort, the numbers were slightly higher in the group randomized to intermediate-dose anticoagulation.
Point 2: Could “Much More” Be Better Than “More” and “Less”?
While this study does suggest that intermediate-dose anticoagulation does not benefit patients admitted to ICU with severe COVID-19 infection, important questions remain unanswered. It’s possible that if full-intensity anticoagulation (ie enoxaparin 1 mg/kg q12h) had been tested rather than intermediate-dose the rates of thrombosis may have been reduced. It’s also plausible that low-molecular weight heparin may not be the most effective anticoagulation strategy for these patients, and perhaps alternatives such as intravenous heparin or a direct-acting anticoagulant (eg fondaparinux) may be superior. While these hypotheses remain to be explored, for the time being intermediate-dose anticoagulation cannot be recommended routinely for patients with severe Covid-19 admitted to the ICU.
Dr Jennings is currently an Associate Professor of Pharmacy at Long Island University and the clinical pharmacist for the Heart Transplant and LVAD teams at New York- Presbyterian Hospital Columbia University Irving Medical Center. He is an active researcher in his field, and he has published over 120 peer-reviewed abstracts and manuscripts, primarily focusing on the pharmacotherapy of patients under mechanical circulatory support. As a recognized expert in this area, he has been invited to speak at numerous national and international venues, including meetings in France, Saudia Arabia, India. Finally, Dr. Jennings has been active in professional organizations throughout his career. He is a fellow of the American College of Clinical Pharmacy, the American College of Cardiology, the Heart Failure Society of America, and the American Heart Association.
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