Anti-epileptic drugs may impact statin efficacy
MedWire News: Physicians should be alert for reduced efficacy of statin treatment in patients with epilepsy being treated with commonly used older-generation antiepileptic drugs, warn researchers.
Barry Gidal (University of Wisconsin, Madison, USA) and colleagues found that patients taking older-style enzyme-inducing antiepileptic drugs (EIAEDs) required more uptitrations of their statin dose than did those taking non-enzyme-inducing AEDs (NEIAEDs).
The team examined insurance claims from 1118 epileptic patients who were also taking a statin. Of these, 45% were taking an EIAED.
During the 12 months after statin initiation, 23% of patients in the EIAED group required an upward statin dose adjustment, compared with 18% of the NEIAED group. After accounting for baseline variables, this amounted to a significant 36% higher risk for needing an increase in statin dose.
Gidal and team explain in the journal Epilepsy Research that older-generation AEDs such as phenytoin, carbamazepine, and the barbiturates induce the cytochrome P450 (CYP) family of enzymes. Thus, interaction with statins, which are metabolized by intestinal and hepatic CYP 3A4, is not unexpected.
Among 35 patients with available 12-month laboratory values, low-density lipoprotein (LDL) cholesterol levels were significantly higher among those taking an EIAED rather than a NEIAED, at averages of 109.97 versus 90.63 mg/dl (2.84 vs 2.34 mmol/l).
Patients taking EIAEDs were 41 times more likely than those taking NEIAEDs to still have above-target LDL cholesterol levels (>100 mg/dl; 2.6 mmol/l) at 12 months (83% vs 26%).
The study was not powered to detect differences in cardiovascular outcomes; however, significantly more patients receiving EIAEDs suffered a stroke during follow-up, relative to those taking NEIAEDs, at 21.5% versus 13.9%.
Gidal et al stress that their study was exploratory in nature, but note: "Clinicians would be prudent to increase their monitoring of any patient using EIAEDs concomitantly with statins, as these patients may require more aggressive statin dosing in order to maintain optimal cholesterol levels."
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By Eleanor McDermid