Effects of lacosamide and carbamazepine on lipids in a randomized trial

Scott Mintzer, Svetlana Dimova, Ying Zhang, Björn Steiniger-Brach, Marc De Backer, Daya Chellun, Robert Roebling, Scott Mintzer, Svetlana Dimova, Ying Zhang, Björn Steiniger-Brach, Marc De Backer, Daya Chellun, Robert Roebling

Abstract

Objective: The effects of anticonvulsants on lipids are the subject of considerable concern and investigation, but there are almost no data on this issue from randomized trials. We evaluated serum lipid profiles in adults with newly diagnosed epilepsy, following randomization to lacosamide (LCM) or carbamazepine (CBZ) monotherapy.

Methods: We analyzed data from a Phase 3, international, randomized, double-blind trial of LCM vs CBZ for the initial treatment of focal epilepsy. Serum lipid profiles in patients not taking lipid-lowering agents and providing blood samples under fasting conditions before treatment, and following 3 or 12 months of treatment with LCM or CBZ at various doses were analyzed.

Results: At 12 months, 271 patients satisfied the inclusion criteria for the analysis. No change was observed in LCM-treated patients for total cholesterol, cholesterol fractions, or triglycerides. CBZ-treated patients showed an increase of 21.1 mg/dL in total cholesterol, 12.6 mg/dL in low-density lipoprotein (LDL) cholesterol, 12.5 mg/dL in non-high density lipoprotein (non-HDL) cholesterol, and 8.5 mg/dL in HDL cholesterol; triglycerides remained unchanged. The proportion of patients with elevated total cholesterol levels (above the upper limit of the reference range) did not change in the LCM treatment group (37.0% at Baseline; 34.8% at 12 months), but increased from 30.8% (at Baseline) to 49.6% (at 12 months) in the CBZ treatment group.

Significance: This study provides Class II evidence that CBZ elevates serum lipids, whereas LCM has no effect on lipids. It supports LCM as an appropriate choice for new-onset focal epilepsy.

Keywords: antiepileptic drug; monotherapy; newly diagnosed epilepsy; serum lipid levels; vascular risk factors.

Conflict of interest statement

Dr Mintzer has served as a speaker and has received research funding from UCB Pharma. Svetlana Dimova, Björn Steiniger‐Brach, Marc De Backer, Daya Chellun, and Robert Roebling are employees of UCB Pharma. Ying Zhang was an employee of UCB Pharma at the time this analysis was conducted. We confirm that we have read the Journal's position on issues involved in ethical publication and affirm that this report is consistent with those guidelines.

© 2020 The Authors. Epilepsia published by Wiley Periodicals LLC on behalf of International League Against Epilepsy.

Figures

Figure 1
Figure 1
Least‐squares mean change in lipid levels from Baseline at 12 mo (ANCOVA) (12‐mo population). The ANCOVA model included treatment as a main effect and age, sex, body mass index, and Baseline lipid level as covariates; an = 131 for CBZ; bn = 138 for LCM, n = 133 for CBZ; cn = 138 for LCM, n = 131 for CBZ. Table includes within treatment group comparison 12‐month vs Baseline, pairedttest; P‐values were based on means of observed values (unadjusted): LCM: Total cholesterol P> .05; LDL cholesterol P > .05; non‐HDL cholesterol P> .05; HDL cholesterol P> .05; triglyceridesP >.05. CBZ: Total cholesterol P<.0001; LDL cholesterol P< .0001; non‐HDL‐cholesterol P< .0001; HDL cholesterol  P< .0001; triglycerides P> .05. ANCOVA, analysis of covariance; CBZ, carbamazepine; HDL, high‐density lipoprotein; LCM, lacosamide; LDL, low‐density lipoprotein
Figure 2
Figure 2
Proportion of patients with total cholesterol and/or low‐density lipoprotein (LDL) cholesterol levels above the upper limit of the reference range at Baseline and 12 mo (12‐mo population). Reference ranges for total cholesterol: normal was 130‐200 mg/dL, high was >200 mg/dL; reference ranges for LDL cholesterol: under 18 y of age, normal was 0‐110 mg/dL, high was >110 mg/dL; above 18 y of age, normal was 0‐130 mg/dL, high was >130 mg/dL. CBZ, carbamazepine; LCM, lacosamide; LDL, low‐density lipoprotein
Figure 3
Figure 3
Proportion of patients with a ≥20 or ≥40 mg/dL increase in total cholesterol, LDL cholesterol, and non‐HDL cholesterol levels from Baseline to 12 mo (12‐mo population). P‐values are from Fisher exact test;an = 131 for CBZ. CBZ, carbamazepine controlled‐release; HDL, high‐density lipoprotein; LCM, lacosamide; LDL, low‐density lipoprotein; TC, total cholesterol

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Source: PubMed

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