ENOrphanet Journal of Rare Diseases | Risk factors, stroke rates and aspirin prescribing trends in the Canadian Fabry disease initiative cohort
Date: April 05, 2025
Classification: Frontiers
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This study reviewed the incidence rate of first stroke or transient ischemic attack (TIA) among Fabry disease (FD) patients, traditional atherosclerotic cardiovascular disease (ASCVD) risk assessment, and aspirin (ASA) prescription trends. It found that FD patients experience stroke/TIA at a significantly higher rate before age 60 compared to the general population, and that ASA primary prevention prescriptions declined after 2018. The study provides new insights into stroke prevention strategies for FD patients.
Literature Overview
The article titled Risk factors, stroke rates and aspirin prescribing trends in the Canadian Fabry disease initiative cohort, published in the Orphanet Journal of Rare Diseases, reviews and summarizes the incidence of first stroke or transient ischemic attack (TIA) among Fabry disease (FD) patients in the Canadian Fabry Disease Initiative (CFDI) cohort, traditional ASCVD risk assessment, and trends in aspirin (ASA) primary prevention prescriptions. The study utilized longitudinal data from 2007 to 2023, comparing FD patients who had not experienced stroke events with those who had. It also assessed ASA/AP prescription trends before and after 2018, finding a decline in ASA use for primary prevention. The data indicate that FD patients experience strokes/TIAs at a much higher rate before age 60 than the general population, despite lower traditional ASCVD risk scores, suggesting a need for more precise primary prevention strategies.
Background Knowledge
Fabry disease is an X-linked recessive genetic disorder caused by mutations in the GLA gene, leading to reduced activity of α-galactosidase A (α-gal A) and intracellular accumulation of globotriaosylceramide (Gb3) and lyso-Gb3, ultimately causing multi-organ damage. The incidence of stroke and TIA in FD patients is significantly higher than in the general population, and the onset age is notably earlier. Although aspirin (ASA) is widely used for primary and secondary prevention of cardiovascular events, its efficacy in FD patients remains unclear. In 2018, three major clinical trials—ARRIVE, ASCEND, and ASPREE—challenged the effectiveness of ASA in primary prevention, prompting an update to Canadian stroke prevention guidelines in 2020 that restricted ASA use for primary prevention. This study aims to evaluate the stroke/TIA incidence, ASCVD risk assessment, and prescription trends in FD patients within the CFDI cohort to inform more precise primary prevention strategies.
Study Methods and Experimental Design
This retrospective study analyzed longitudinal data from 641 FD patients in the CFDI cohort between 2007 and 2023, of which 57 experienced a first stroke or TIA during the study period. The study compared stroke/TIA incidence across gender, GLA mutation types (classic or attenuated), and age groups (<40, 40–59, ≥60 years). It also assessed 10-year ASCVD risk using the 2013 ACC/AHA risk calculator and examined changes in ASA/AP prescriptions before and after 2018. Data were sourced from clinical records, brain MRI/CT reports, laboratory parameters (lyso-Gb3, eGFR, LVMI), and traditional cardiovascular risk factors (e.g., hypertension, smoking, diabetes). Statistical analysis was performed using chi-square tests, McNemar’s tests, and Wilcoxon rank-sum tests, with statistical significance defined as p < 0.05.
Key Findings and Conclusions
Research Implications and Future Directions
This study highlights the limitations of traditional ASCVD risk assessment tools in FD patients and suggests the need for FD-specific risk calculators incorporating GLA mutation type, white matter lesion burden, and other novel biomarkers. Additionally, the uncertain benefit of ASA in primary stroke prevention among FD patients indicates the potential value of alternative antiplatelet agents or strategies (e.g., cilostazol) for lacunar stroke prevention. Further investigation into the underlying mechanisms of small vessel disease in FD patients is warranted to guide individualized treatment approaches.
Conclusion
Basing on data from the Canadian Fabry Disease Initiative (CFDI) cohort, this study analyzed the incidence of stroke/TIA, traditional ASCVD risk assessment, and aspirin (ASA) prescription trends in FD patients. Despite generally low 10-year ASCVD risk scores, FD patients experience stroke/TIA at a significantly higher rate before age 60 than the general population, especially among males and those with classic GLA mutations. Following the publication of the 2018 ARRIVE, ASCEND, and ASPREE clinical trials, the proportion of FD patients using ASA for primary prevention declined in the CFDI cohort, though some patients continued to receive prescriptions, suggesting clinicians still perceive potential benefits in specific FD cases. The study also found that most stroke events in FD patients are lacunar or cryptogenic and occur without clear coronary artery disease or ASCVD risk factors, indicating a pathogenic mechanism distinct from traditional atherosclerosis, possibly involving small vessel disease and endothelial dysfunction. Therefore, future research should focus on developing more tailored stroke risk assessment tools for FD patients and exploring the potential of non-ASA agents in primary prevention. This study provides critical clinical evidence for stroke prevention strategies in Fabry disease, emphasizing the importance of personalized treatment and mechanism-driven interventions.
