A National Level Case-Control Study for Determining Risk of Major Cardiovascular Events in People with Epilepsy

Abstract

IntroductionThe risk of cardiovascular events amongst people with epilepsy who are receiving enzyme-inducing anti-epileptic drugs (EIAEDs) seems to be higher than those on other medications and the general population. National-level record linkage enables development of case-control studies at a wider scope accounting for multiple factors.
 Objectives and ApproachPeople with epilepsy were identified between 2003-01-01 and 2017-12-31 and were matched to a control group on: age, gender, deprivation quintile and year of diagnosis, accounting for any changes in clinical therapeutic guidelines. Primary and secondary care population records were linked to capture relevant comorbidities and major cardiovascular events. Annual district birth and death extract were used in combination with the Welsh Demographic Service (WDS) dataset to capture demographic and cardiovascular related death records. The WDS dataset was used to identify eligible control groups for each case and a linkage approach between the control and case database was developed for matching cases and controls with replacement and randomization. Survival analysis was conducted to evaluate the difference in time to first major cardiovascular event in patients receiving EIAED versus Non-EIAEDs and controls.
 Results10,241 cases (mean age 49.6 years, 52.2% male) with diagnosis of epilepsy were matched to 35,145 controls. 3,180 (31.1%) cases received EIAEDs and 7,061 (68.9%) received non-EIAEDs. The risk of experiencing a major cardiovascular event was higher in cases compared to controls (adjusted hazard ratio 1.52,95%CI[1.50–1.55];p<0.001). There was no significant difference in cardiovascular events between those treated with non-EIAEDs and EIAEDs (adjusted hazard ratio 1.04,95%CI[0.95-1.12];p=0.407).
 Conclusion / ImplicationsData linkage provides a unique opportunity and insight into studying disease risk factors. We have shown that individuals with epilepsy prescribed antiepileptic drugs, re at an increased risk of a major cardiovascular events regardless of treatment type (EIAED,NEIAED) compared with a matched control population.