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  • Effects of new antiepileptic drugs on circulatory markers for vascular risk in patients with newly diagnosed epilepsy.

Effects of new antiepileptic drugs on circulatory markers for vascular risk in patients with newly diagnosed epilepsy.

Epilepsia (2013-08-29)
Dong Wook Kim, Seo-Young Lee, Young-Min Shon, Ji Hyun Kim
ABSTRACT

Although it is well documented that long-term therapy with older antiepileptic drugs (AEDs) leads to an increase in risk for atherosclerosis, there has been only limited information regarding the vascular risk in patients who are treated with new AEDs. We therefore conducted a prospective longitudinal study to assess the potential effects of new AEDs on the circulatory markers for vascular risk in patients with newly diagnosed epilepsy. We recruited adult patients with epilepsy who began to receive monotherapy with one of the new AEDs, including levetiracetam (LEV), oxcarbazepine (OXC), and topiramate (TPM). Circulatory markers of vascular risk were measured twice before and after 6 months of AED monotherapy. A total of 109 patients completed the study (LEV, n = 40; OXC, n = 40; TPM, n = 29). Six months of monotherapy resulted in significant increases in low-density lipoprotein cholesterol (LEV, from 90.2 to 98.5 mg/dl, 9.2% increase, p = 0.025; OXC, from 96.5 to 103.2 mg/dl, 7.0% increase, p = 0.049), homocysteine (LEV, from 7.9 to 10.4 μm, 31.6% increase, p = 0.001; OXC, from 8.7 to 11.5 μm, 32.2% increase, p < 0.001; TPM, from 8.3 to 12.3 μm, 48.2% increase, p < 0.001), apolipoprotein B (LEV, from 63.6 to 77.4 mg/dl, 21.7% increase; OXC, from 67.0 to 83.2 mg/dl, 24.2% increase; TPM, from 66.7 to 84.4 mg/dl, 26.5% increase; all p < 0.001), and apolipoprotein B/apolipoprotein A1 ratio (LEV, from 0.51 to 0.61, 19.6% increase; OXC, from 0.52 to 0.67, 28.8% increase; TPM, from 0.50 to 0.67, 34.0% increase; all p < 0.001). Serum apolipoprotein A1 and folate were significantly decreased in TPM (from 139.1 to 132.1 mg/dl, 5.0% decrease, p = 0.014) and OXC (from 8.1 to 6.4 ng/ml, 21.0% decrease, p = 0.046) groups, respectively. There were no significant changes in total cholesterol, triglyceride, high-density lipoprotein cholesterol, lipoprotein(a), and vitamin B12 in all three groups. Our findings suggest that treatment with some new AEDs might be associated with alterations in circulatory markers of vascular risk, which could contribute to the acceleration of atherosclerosis and increased risk of vascular diseases.

MATERIALS
Product Number
Brand
Product Description

Supelco
Topiramate solution, 1.0 mg/mL in methanol, ampule of 1 mL, certified reference material, Cerilliant®
Supelco
Oxcarbazepine solution, 1.0 mg/mL in acetonitrile, ampule of 1 mL, certified reference material, Cerilliant®
USP
Levetiracetam Racemic Mixture, United States Pharmacopeia (USP) Reference Standard
Sigma-Aldrich
Carbamazepine, meets USP testing specifications
Sigma-Aldrich
L-Homocysteine, ≥98.0% (NT)
Levetiracetam impurity D, European Pharmacopoeia (EP) Reference Standard
Supelco
Carbamazepine, Pharmaceutical Secondary Standard; Certified Reference Material
Sigma-Aldrich
Piracetam
Sigma-Aldrich
Oxcarbazepine, ≥98% (HPLC), solid
Supelco
Levetiracetam solution, 1.0 mg/mL in methanol, ampule of 1 mL, certified reference material, Cerilliant®
Supelco
Carbamazepine solution, 1.0 mg/mL in methanol, ampule of 1 mL, certified reference material, Cerilliant®
Sigma-Aldrich
Topiramate, ≥98% (HPLC), solid
Levetiracetam, European Pharmacopoeia (EP) Reference Standard