Risk factors, stroke rates and aspirin prescribing trends in the Canadian Fabry disease initiative cohort.

BACKGROUND

Fabry disease (FD) is an X-linked disorder caused by deleterious variants in GLA. Cardiovascular disease (CVD) causes premature mortality in FD. Hope for aspirin (acetylsalicylic acid, ASA) to reduce CVD risks in FD as primary prevention may have been tempered by the 2018 ARRIVE, ASCEND, and ASPREE clinical trials. It is unclear how new ASA guidance applies to FD patients, who have a high rate of young-onset, small vessel stroke compared with the general population.

METHODS

Longitudinal data spanning 2007-2023 from patients in the Canadian Fabry Disease Initiative (CFDI) were analyzed retrospectively. Incident stroke and transient ischemic attack (TIA), other CVD events, FD-specific risk factors, and ASA/antiplatelet ("ASA/AP") prescription before and after 2018 were compared between groups who never had an event ("primary prevention group") to those who had incident stroke/TIA during the study. Stroke/TIA rates were compared within CFDI by sex and GLA variant severity, and in the CFDI compared to Canadian statistics by sex. Ten-year atherosclerotic CVD (ASCVD) risk was calculated using the 2013 ACC/AHA risk calculator. ASA/AP prescription rate was compared before and after 2018.

RESULTS

Out of 641 patients, 57 had an incident stroke/TIA during the study, and 193 with complete data remained in the primary prevention group. Stroke/TIA rates were significantly higher among male patients (0.026 events per patient-year) than females (0.0098 events per patient-year), and higher among patients with severe GLA variants (males: 0.031 events per patient-year, females: 0.0096 events per patient-year) compared to those with attenuated variants (males: 0.011 events per patient-year, females: 0.0088 events per patient-year). No patients under 60 years at their incident stroke/TIA had high (≥ 10%) calculated 10-year ASCVD risk. Fewer patients were prescribed ASA/AP for primary prevention after 2018.

CONCLUSIONS

There was a high incidence of stroke/TIA in the younger CFDI cohort compared to the general Canadian population, despite low levels of traditional vascular risk factors as represented in 10-year estimated ASCVD risk. Primary prevention use of ASA has declined.