Antithrombotic Therapy Fails to Prevent Stroke in COVID-19

Daniel M. Keller, PhD

October 21, 2021

Editor's note: Find the latest COVID-19 news and guidance in Medscape's Coronavirus Resource Center.

Anticoagulation and/or antiplatelet therapy with a variety of agents does not prevent acute ischemic stroke (AIS) in elderly patients with COVID-19 and comorbidities, new research suggests.

Since early in the pandemic, COVID-19 has been associated with a hypercoagulable state, and these patients have routinely received antiplatelet and/or anticoagulation therapy, investigators note.

However, results from a cohort study show that "prophylactic antiaggregation" with low-molecular weight heparin (LMWH) or oral anticoagulation "did not statistically reduce stroke risk" in patients with COVID-19, co-investigator Martina Di Pietro, MD, a neurology resident at SS. Annunziata Hospital, Chieti, Italy, told meeting attendees.

The findings were presented at the virtual World Congress of Neurology (WCN) 2021.

Possible Mechanisms of Action

In several previously published studies, the incidence of AIS ranged from 0.9% to 2.7% in those with COVID-19, and the incidence was 1.2% in a pooled analysis of data for 54 cases among 4466 patients, Di Pietro noted.

One of the studies calculated a more than sevenfold greater risk of AIS among patients with COVID-19 compared with patients with influenza (odds ratio, 7.6; 95% CI, 2.3 - 25.2).

Di Pietro noted three mechanisms that may be contributing to the increased risk for AIS accompanying COVID-19: binding of the virus to the ACE2 receptor on blood vessel walls causing vasculitis, cardioembolism, or paradoxical embolism, and the well-known hypercoagulability state that occurs with COVID-19.

She reasoned that if cardioembolism or paradoxical embolism were the cause of the strokes, anticoagulation should have a preventive effect. If platelet hyperaggregability played a role, antiplatelet agents could be beneficial.

Thus, the aim of the current study was to investigate the role of thromboprophylaxis in the primary prevention of cerebrovascular events among patients with COVID-19.

A cohort of 240 of these patients was assessed between March 2020 and March 2021 to evaluate whether previously prescribed antithrombotic prophylaxis protected them from the occurrence of AIS, and in particular, whether antiaggregation or anticoagulation therapy was the more effective prevention strategy.

No Risk Reduction

Of the study participants, all of whom had COVID-19, 11 (4.6%) also developed AIS. Nine of these patients with AIS were women and their median age was 80 years.

The patients had previous cardiovascular risk factors. Nine had severe interstitial pneumonia, four had multiple cerebral infarctions, and two had no evidence of vascular occlusion or arteritis. Among the cardiovascular risk factors, the most common was hypertension, followed by atrial fibrillation, diabetes, cardiopathy, and carotid stenosis.

Participants with AIS received a variety of antithrombotic therapies, including aspirin (n = 3), LMWH plus aspirin (n = 2), a novel oral anticoagulant plus aspirin (n = 1), warfarin (n = 1), and prophylactic doses of LMWH (n = 3). One participant was not receiving any antithrombotic agent.

Five of these patients were discharged home or to another care facility, while the other six died in hospital.

Because prophylactic antiaggregation or anticoagulation therapy failed to reduce risk for AIS in COVID-19, and given the prothrombotic effect from activation of the ACE2 receptor, Di Pietro noted that possibly blocking the binding of SARS-CoV-2 to the receptor could be beneficial.

She also suggested that angiographic and postmortem studies of the cervico-cerebral vasculature may shed light on the role of vasculitis as a potential mechanism of AIS.

COVID-19 or Other Factors?

Commenting on the study for Medscape Medical News, Louise McCullough, MD, PhD, chair of the Department of Neurology with McGovern Medical School at The University of Texas Health Science Center at Houston, noted that the most important finding was the 4.6% prevalence of AIS among the study cohort.

"But is it due to the COVID itself?" asked McCullough, who was not involved with the research.

She noted that many of the patients had traditional risk factors, such as hypertension, atrial fibrillation, and diabetes, "all of which can lead to stroke." In addition, "these patients were also quite old," she said.

McCullough did not dismiss the idea that COVID-19 itself may lead to stroke, but she said it may just provoke inflammation, which also increases risk for stroke.

She also noted that with only 11 patients who had stroke, and the fact that they received a variety of anticoagulant and antiplatelet agents, it is impossible to assess which may be the best therapy to use.

McCullough said that future studies should use matched samples of patients with equally severe disease, such as with acute respiratory distress syndrome or other pulmonary infections not related to COVID-19, and assess the stroke rate in those patients.

Di Pietro and McCullough have reported no relevant financial relationships.

WCN 2021. Presented October 3-7, 2021.

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