COVID-19 and Risk of Acute Ischemic Stroke Among Medicare Beneficiaries Aged 65 Years or Older: Self-Controlled Case Series Study

Abstract

Background and objectives: Findings of association between coronavirus disease 2019 (COVID-19) and stroke remain inconsistent, ranging from significant association to absence of association to less than expected ischemic stroke among hospitalized patients with COVID-19. The current study examined the association between COVID-19 and risk of acute ischemic stroke (AIS).

Methods: We included 37,379 Medicare fee-for-service (FFS) beneficiaries aged ≥65 years diagnosed with COVID-19 from April 1, 2020, through February 28, 2021, and AIS hospitalization from January 1, 2019, through February 28, 2021. We used a self-controlled case series design to examine the association between COVID-19 and AIS and estimated the incidence rate ratios (IRRs) by comparing incidence of AIS in risk periods (0-3, 4-7, 8-14, 15-28 days after diagnosis of COVID-19) vs control periods.

Results: Among 37,379 Medicare FFS beneficiaries with COVID-19 and AIS, the median age at diagnosis of COVID-19 was 80.4 (interquartile range 73.5-87.1) years and 56.7% were women. When AIS at day of exposure (day = 0) was included in the risk periods, IRRs at 0-3, 4-7, 8-14, and 15-28 days following COVID-19 diagnosis were 10.3 (95% confidence interval 9.86-10.8), 1.61 (1.44-1.80), 1.44 (1.32-1.57), and 1.09 (1.02-1.18); when AIS at day 0 was excluded in the risk periods, the corresponding IRRs were 1.77 (1.57-2.01) (day 1-3), 1.60 (1.43-1.79), 1.43 (1.31-1.56), and 1.09 (1.01-1.17), respectively. The association appeared to be stronger among younger beneficiaries and among beneficiaries without prior history of stroke but largely consistent across sex and race/ethnicities.

Discussion: Risk of AIS among Medicare FFS beneficiaries was 10 times (day 0 cases in the risk period) as high during the first 3 days after diagnosis of COVID-19 as during the control period and the risk associated with COVID-19 appeared to be stronger among those aged 65-74 years and those without prior history of stroke.

Classification of evidence: This study provides Class IV evidence that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is associated with increased risk of AIS in the first 3 days after diagnosis in Medicare FFS beneficiaries ≥65 years of age.

Figure 1

Flowchart of US Medicare FFS Beneficiaries With Diagnosed COVID-19 and Acute Ischemic Stroke, 2019–2021

Figure 2

Graphic Representation of Self-Controlled Case Series Study Design