CARBAMAZEPINE AND ATHEROSCLEROSIS: IS THERE ANY LINK? [P07.006]
Mubashira Hashmi, Shaista Anwar Siddiqi, Abdul Malik, Sarah Saleem, Farrukh Shohab Khan, Karachi, Sindh, Pakistan
The antiepileptic drugs (AEDs) carbamazepine and phenytoin induce the activity of hepatic cytochrome P450 enzymes that are important in cholesterol synthesis.1 These agents have been shown to significantly alter lipid profiles in ways that may promote arteriosclerosis, including the elevation of total cholesterol (TC), low-density lipoprotein (LDL) cholesterol, and triglycerides.2 It has also been noted that switching patients from carbamazepine or phenytoin to another AED that is not an enzyme inducer (eg, lamotrigine or levetiracetam) reduced elevated lipid values in patients with epilepsy.1 There is continuing concern that long-term anticonvulsant therapy does increase the actual development of atherosclerosis.3
In this study, Hashmi et al examined fasting lipid profiles from 37 patients with epilepsy who were treated with carbamazepine for at least 3 months, and from 37 healthy control subjects who were not exposed to carbamazepine. The patients varied in age from 2 to 25 years. The carbamazepine-exposed patients exhibited relatively small but statistically significant increases in TC, triglyceride, and high-density lipoprotein (HDL) cholesterol values in comparison with the nonexposed control subjects (Table).4 LDL cholesterol did not differ significantly between the patients and healthy control subjects. None of the mean lipid values exceeded the normal range established by the National Cholesterol Education Program.
Table. Effects of Carbamezepine Exposure on Lipid Parameters (37 Patients with Epilepsy vs 37 Healthy Control Subjects)
Parameter |
Exposed, mean mg/dL |
Nonexposed, mean mg/dL |
P Value |
Normal Range |
| |
Total cholesterol |
165.2 |
148.8 |
.03 |
<200 mg/dL |
Triglyceride |
118.2 |
85.4 |
.02 |
<150 mg/dL |
High-density lipoprotein |
40.7 |
37.4 |
.005 |
40–60 mg/dL |
Low-density lipoprotein |
102.2 |
94.4 |
.22 |
<100 mg/dL |
Data from Normal range: National Cholesterol Education Program. Available at: http://www.nhlbi.nih.gov/guidelines/cholesterol/atglance.pdf. Accessed May 30, 2009.4
Treatment with carbamazepine appeared to improve HDL values. Low HDL (<40 mg/dL) was noted for 15 of 37 patients (41%) in the carbamazepine-exposed group and 29 of the 37 patients (78%) in the nonexposed group (P = .001).
Lipid values were used to calculate atherogenic risk ratios, including the ratio of TC to HDL and of LDL to HDL. The TC/HDL ratio was 4.10 for patients in the carbamazepine-exposed group and 3.98 for those in the nonexposed group (not statistically significant). Similarly, the LDL ratio was 2.53 for the exposed group and 2.53 for the nonexposed group (again, not statistically significant). No significant relationships were observed between lipid values and patient demographic characteristics such as age, sex, diet, or body mass index.
The investigators concluded that significant lipid alterations were observed in carbamazepine-treated patients with epilepsy in comparison with healthy control subjects. However, due to raised HDL levels, neither the TC/HDL ratio nor the LDL/HDL ratio differed significantly between the exposed and nonexposed groups. Because the control group in this study consisted of healthy subjects who were not exposed to carbamazepine, and pretreatment lipid values for the patients with epilepsy were not reported, it is unclear whether the alterations reported in this poster reflect the effects of carbamazepine, comorbid medical conditions or their treatments, or even metabolic changes associated with epilepsy itself. Similar observations were reported in a recent study in children, in which 3 months of treatment with carbamazepine significantly increased LDL and triglycerides, but with no significant improvement in HDL levels.5 Further studies evaluating strategies to actually evaluate the risk, as well as potential studies aimed at minimizing the risk, either through medication changes or perhaps the use of vitamins, are necessary.6
References
1. Mintzer S, Skidmore CT, Abidin CJ, et al. Effects of antiepileptic drugs on lipids, homocysteine, and C-reactive protein. Ann Neurol. 2009;65:448-456.
2. Brämswig S, Sudhop T, Luers C, et al. Lipoprotein(a) concentration increases during treatment with carbamazepine. Epilepsia. 2003;44:457-460.
3. Tan TY, Lu CH, Chuang HY, et al. Long-term antiepileptic drug therapy contributes to the acceleration of atherosclerosis. Epilepsia. 2009 Mar 9. [Epub ahead of print.]
4. Normal range: National Cholesterol Education Program. Available at: http://www.nhlbi.nih.gov/guidelines/cholesterol/atglance.pdf. Accessed May 30, 2009.
5. Aggarwal A, Singh V, Batra S, et al. Effect of carbamazepine therapy on serum lipids in children with partial epilepsy. Pediatr Neurol. 2009;40:94-97.
6. Hamed SA, Nabeshima T. The high atherosclerotic risk among epileptics: the atheroprotective role of multivitamins. J Pharmacol Sci. 2005;98:340-353.
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