Enzyme-iInducing Antiseizure Drug Use Is Associated with Dose Dependent Long-term Cardiovascular Disease in Adults with Epilepsy
Abstract number :
3.295
Submission category :
7. Anti-seizure Medications / 7D. Drug Side Effects
Year :
2021
Submission ID :
1825497
Source :
www.aesnet.org
Presentation date :
12/6/2021 12:00:00 PM
Published date :
Nov 22, 2021, 06:44 AM
Authors :
Colin Josephson, MD, MSc, MSc, FRCPC, CSCN (EEG) - University of Calgary; Guillermo Delgado-Garcia, MD MSc - University of Calgary; Spiros Denaxas, PhD - University College London; Arturo Gonzalez-Izquierdo, PhD - University College London; Mark Keezer, MDCM PhD - Universite de Montreal; Mubasiru Lamidi, MSc - University of Calgary; Tolulope Sajobi, PhD - University of Calgary; Meng Wang, MSc - University of Calgary; Samuel Wiebe, MD MSc - University of Calgary
Rationale: Enzyme-inducing antiseizure medications (eiASMs) have been hypothesized to be associated with long-term risks of cardiovascular disease. The objective of this study was to quantify and model this putative hazard of cardiovascular disease.
Methods: We used the population-based the CALIBER © resource with linked primary and hospital data to isolate three cohorts, one comprising all adults meeting a case definition for epilepsy diagnosed after 1990, one comprising incident cases diagnosed after 1998 (hospital linkage date), and one limited to adults diagnosed with epilepsy at age ≥65. Exposure was receipt of four consecutive eiASMs following an epilepsy diagnosis and the outcome was incident cardiovascular disease (ischaemic heart disease or ischaemic or haemorrhagic stroke). The hazard of incident cardiovascular disease was evaluated using an adjusted propensity matched survival analysis. We also determined the long-term effect of chronic exposure using weighted cumulative exposure models.
Results: Of 10,916,166 adults, we identified 50,888 (0.6%) period prevalent cases, of whom 31,466 (62%) were diagnosed on or after 1990 and were free of cardiovascular disease at baseline. In a propensity matched Cox proportional hazards model adjusted for age, sex, baseline socioeconomic status, and cardiovascular risk factors, the hazard of incident cardiovascular disease was 1.21 (95% confidence interval 1.06-1.39) for those receiving eiASMs compared to non-eiASMs. The absolute difference in cumulative hazard appeared to diverge significantly after 8-10 years. Median hazard ratio increased from 1.54 when taking a relative defined daily dose (rDDD) of an eiASM of 1 to 2.38 with a rDDD of 2 over a maximum of 25 years follow-up compared to those not receiving an eiASM. The hazard was elevated but attenuated when restricting analyses to incident cases or those diagnosed after age 65.
Conclusions: There is a clinically meaningful hazard of incident cardiovascular disease in those receiving eiASMs. The effect is dose dependent and the absolute difference in hazard seems to reach clinical significance by approximately 10 years from first exposure.
Funding: Please list any funding that was received in support of this abstract.: N/A.
Anti-seizure Medications