Patients infected with SAR-CoV2 present with numerous neurological signs and symptoms including IS. Rates of stroke among COVID-19 patients have ranged from 1.1% to 3%. Additional concerns in COVID-19 patients include that they may have an increased risk of bleeding, which may predispose them to hemorrhagic transformation of IS. IV-tPA is the gold standard in acute IS (AIS) management. However, little is known about the safety and efficacy of IV-tPA in COVID-19 patients with acute stroke.

CASCADE was a prospective, international (Iran, Greece, Germany), multicenter, cohort study conducted from February 18, 2019, to December 31, 2020, that assessed the safety and outcomes of IV-tPA in patients aged 18 years or older with acute IS (AIS) with and without COVID-19. Consecutive AIS patients treated with IV-tPA were included in the study. Diagnosis of COVID-19 was made within 2 weeks prior to or following admission.

The primary outcome of the study was disability at discharge (Modified Rankin Scale [mRS] score >2), hemorrhagic transformation, and in-hospital mortality rates among all patients. Secondary outcomes included stroke severity (assessed using the National Institutes of Health Stroke Scale [NIHSS]), door-to-needle time for the administration of IV-tPA, and length of hospital stay. Computed tomography of the head was performed at 12 to 36 hours of all patients who received IV-tPA. Hemorrhagic transformation was defined and categorized based on location and volume. Symptomatic intracranial hemorrhage (sICH) occurred when there was hemorrhagic transformation and worsening of symptoms (NIHSS increase of >4). In cases in which NIHSS scores were not readily available, symptomatic disease was based on the neurologists' judgment.

A total of 545 stroke patients were included in this study. Of these patients, 101 (18.5%) had COVID-19 and 444 (81.5%) patients were COVID-19-negative. The mean age of the study population was 58 years, and over half were male. At baseline, COVID-19 stroke patients had lower lymphocyte counts but higher polymorphonuclear neutrophil, high C-reactive protein, erythrocyte sedimentation rate, aspartate aminotransferase, and alanine aminotransferase levels. The most common etiology of stroke in the overall population was large-artery atherosclerosis, which was disproportionately higher in the COVID-19 population (47.3%) then in the total stroke population (31.5%).

Investigators found that length of hospitalization was significantly longer in COVID-19 versus non-COVID-19 patients (hazard ratio [HR] = 1.78, 95% CI 1.31-2.25). COVID-19 patients had more severe stroke on admission based on NIHSS. According to the mRS data available (mRS scores were missing for 133 alive cases), there was no difference in stroke disability between COVID-19 and non-COVID-19 stroke patients (odds ratio [OR] = 0.5, 95% CI 0.09-2.64). While a crude model estimate of mortality showed higher death rates in COVID-19 stroke patients, this was not confirmed when a multiple Bayesian model was applied (OR = 3.06, 95% CI 0.83-6.60).

Seventeen stroke patients died, including five with COVID-19. A composite score of the odds of disability at discharge and mortality did not differ between the two groups. After adjusting for confounding, no differences were observed in discharge disability scores (mRS >2), in-hospital mortality, and hemorrhagic transformation between stroke patients with and without COVID-19.

The authors concluded that IV-tPA use was not associated with an increased risk of disability, mortality, or hemorrhagic transformation when used in AIS in patients with COVID-19 compared with AIS patients without COVID-19. They recommended that the use of IV-tPA be the standard of care for the management of AIS in COVID-19 patients. This paper provides useful information for pharmacists caring for AIS patients with COVID-19.

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