Anticoagulation reduces risk for thrombosis, death after COVID-19 hospitalization
Patients hospitalized with COVID-19 remain at higher risk for thromboembolic events and death after discharge than previously thought, according to study results published in Blood.
“Until our registry was published, there had been controversy as to whether this risk extended after hospitalization,” lead researcher Alex C. Spyropoulos, MD, FACP, FCCP, FRCPC, professor at the Institute of Health System Science at Feinstein Institutes for Medical Research and director of anticoagulation and clinical thrombosis services at Northwell Health, told Healio. “The reason is because prior to our publication, there was essentially much lower-quality data stemming from retrospective analyses, usually from claims databases.”
The prospective, multicenter CORE-19 registry designed by Spyropoulos and colleagues included 4,906 adults (mean age, 61.7 years; 53.7% men) hospitalized with COVID-19 at Northwell Health hospitals between March 1 and May 31, 2020.
The researchers sought to detect venous thromboembolism events — such deep vein thrombosis, pulmonary embolism and arterial thromboembolism — among patients discharged from the hospital within 90 days.
They found VTE, arterial thromboembolism and all-cause mortality occurred more frequently than originally believed, in 7.13% of cases. Moreover, post-discharge anticoagulants — primarily at prophylactic doses — decreased risk for major thromboembolic events and death by 46% (OR = 0.54; 95% CI, 0.47-0.81).
Spyropoulos spoke with Healio about the implications of his findings, particularly in light of increasing COVID-19 cases driven by the delta variant.
Healio: How did you conduct this study?
Spyropoulos: We very deliberately designed a prospective registry. At one point, we represented the epicenter of the pandemic in the United States. A huge number of patients with COVID-19 were hospitalized in our 23 hospitals. We prospectively followed almost 5,000 patients, and later called them to check on their status and see if they had experienced a thrombotic event. Prospective registry data is much higher quality than retrospective data. This required a lot of work, but we got high-quality data at the end of it.
Healio: What did you find?
Spyropoulos: We saw an elevated risk for thrombosis and death among the 4,906 patients we followed after discharge. This included a 1.55% rate of venous clots, 1.71% rate of arterial clots, and 4.83% rate of all-cause mortality. There also was a 1.7% increased risk for major bleeding, which also was higher than we expected.
After we captured these rates, we assessed factors that predicted increased risk for either thrombosis or death in the population. We saw what we thought we may find. Risk factors included advanced age and the presence of underlying cardiovascular disease or underlying chronic kidney disease. Patients in the ICU who survived to be discharged also had increased risk, in addition to patients who had an elevated IMPROVE VTE score of 4 or more (IMPROVE is a validated VTE risk model in patients with COVID-19).
Lastly — and I consider this crucial — ours was the first study to show that post-discharge anticoagulation reduced the risk for thrombosis and death by 46%. Only about 13% of patients received post-surgical prophylaxis, but we were still able to reduce thrombosis and mortality by almost half. I think this has major implications.
Healio: Will prophylactic anticoagulation after discharge become standard of care?
Spyropoulos: Two randomized trials — the ACTIVE IVc trial and the MICHELLE trial — are looking at use of post-discharge anticoagulants vs. placebo among patients with COVID-19. Once the results of those two trials come out, we will have robust, definitive, high-quality data. Until then, in my estimation, patients who have the risk factors I mentioned should be considered for post-discharge prophylaxis.
Healio: Now that more people are vaccinated against COVID-19, will post-discharge protocols for these patients become less relevant?
Spyropoulos: We are out of the woods, but not out of the forest until we check back in December and see no evidence of resurgence. We must worry about variants, especially the delta variant, which we think is more infective and causes greater morbidity. So, these data are still very, very relevant for a patient who is currently hospitalized with COVID-19. I think future research will explore whether there are other biomarkers, in addition to the clinical biomarkers, that predict risk. Very elevated D-dimers might be something we evaluate in terms of that risk.
Healio: Is there anything you’d like to add?
Spyropoulos: This topic reminds us that even when COVID passes, a subset of medically ill patients — including those with sepsis and pneumonia — would benefit from post-discharge prophylaxis.
For more information:
Alex C. Spyropoulos, MD, FACP, FCCP, FRCPC, can be reached at 2001 Marcus Ave., Suite S160, New Hyde Park, NY 11042; email: firstname.lastname@example.org.