The Relationship Between Valproate and Lamotrigine/Levetiracetam Use and Prognosis in Patients With Epilepsy and Heart Failure: A Danish Register-Based Study

• Published in: Journal of cardiac failure 2022-04, Vol.28 (4), p.630-638
• Main Authors: Liang, David, Gardella, Elena, Kragholm, Kristian, Polcwiartek, Christoffer, Sessa, Maurizio
• Format: Article
• Language: English
• Subjects: Aged; Anticonvulsants - adverse effects; antiseizure medications; Cohort Studies; Denmark - epidemiology; Epilepsy; Epilepsy - drug therapy; Epilepsy - epidemiology; heart failure; Heart Failure - drug therapy; Heart Failure - epidemiology; Humans; Lamotrigine - therapeutic use; Levetiracetam - therapeutic use; older patients; Prognosis; Valproic Acid - therapeutic use
• ISSN: 1071-9164; 1532-8414
• DOI: 10.1016/j.cardfail.2021.07.020

•The choice of antiseizure medication may influence the prognosis of patients 65 yearsof age or older with epilepsy and with heart failure.•Valproate in patients with cardiovascular comorbidity is associated with a higher hazard of mortality due to all causes and to heart failure when compared to treatment with newer drugs, such as lamotrigine and levetiracetam.•The subgroup, 75 years of age, exposed to valproate and redeeming large prescriptions of paracetamol, was identified to be the subgroup with the highest proportion of death. To compare the hazard for all-cause mortality and mortality due to heart failure (HF) between valproate (VPA) and levetiracetam (LEV)/lamotrigine (LTG) users in patients aged ≥ 65 with comorbidities of epilepsy and HF. This was a cohort study using Danish registers during the period from January 1996 to July 2018. The study population included new users of LTG, LEV or VPA. A Cox regression model was used to compute crude and adjusted hazard ratios for the outcome, using an intention-to-treat approach. Average treatment effects (eg, 1-year absolute risks), risk differences and the ratio of risks were computed using the G-formula based on a Cox regression model for the outcomes at the end of the follow-up period. We included 1345 subjects in the study population. VPA users (n = 696), when compared to LTG/LEV users (n = 649), had an increased hazard of mortality due to HF (hazard ratio [HR] 2.39; 95% CI 1.02–5.60) and to all-cause mortality (HR 1.37; 95% CI 1.01–1.85) in both crude and adjusted analyses. The 1-year absolute risks for all-cause mortality were 29% (95% CI 25%–33%) and 22% (95% CI 18%–26%) for VPA and LTG/LEV users. For mortality due to HF, 1-year absolute risks were 5% (95% CI 3%–7%) and 2% (95% CI 1%–4%) for VPA and LTG/LEV users. The average risk ratio, with LTG/LEV as the reference group, was 1.31 (95% CI 1.02–1.71) for all-cause mortality and 2.35 (95% CI 1.11–5.76) for HF mortality. In older people with HF and epilepsy, treatment with VPA was associated with a higher risk of all-cause and HF mortality compared to treatment with LTG and LEV. (A) Schematic representation of the study design. (B) Density plot of the propensity score to highlight exchangeability of treatments and comparability of cohorts. (C) Cumulative hazard of all-cause mortality. (D) cumulative hazard of mortality caused by heart failure. [Display omitted]