ORLANDO — Patients who experienced sudden cardiac death had a significantly higher rate of treatment with a sodium-channel blocking, anticonvulsant drug, compared with people who did not have sudden death, in a case-control study of more than 10,000 people.
“This finding may explain a proportion of the sudden deaths seen in epilepsy patients,” Dr. Abdennasser Bardai said at the annual scientific sessions of the American Heart Association.
About 10% of epilepsy patients have an unexpected death that is not seizure related—a phenomenon so common that it's been named “sudden unexplained death in epilepsy.” Dr. Bardai and his associates hypothesized that many of these deaths might be triggered by anticonvulsant drugs, especially those that block sodium channels such as carbamazepine, lamotrigine, and phenytoin. Although the sodium-channel blockade these drugs cause is aimed at neurons, the same property can also affect cardiac cells and may potentially cause arrhythmia.
To explore a possible link between anticonvulsant use and sudden death, the researchers used data collected in the Netherlands' Integrated Primary Care Information database. They focused on medical records for people aged 18 or older during 1995–2007 in cases for which at least 1 year's record existed.
Among the more than 478,000 people who met these criteria, 926 experienced sudden death, defined as a natural death heralded by a sudden loss of consciousness within 1 hour after the onset of acute symptoms, or an unwitnessed, unexpected death of someone seen in stable medical condition less than 24 hours before with no evidence of a noncardiac cause. The researchers matched each case with about 20 other people from the database with a similar age and identical gender, reaching a total of 9,832 controls. The average age of the cases and controls was 72 years, and 26% were men.
In a multivariate analysis that controlled for age, gender, smoking, alcohol abuse, concomitant medications, cardiovascular disease, arrhythmia, hypertension, diabetes, heart failure, and hypercholesterolemia, people who died from sudden death were 2.5-fold more likely to be on treatment with an anticonvulsant drug than were controls, a statistically significant difference, reported Dr. Bardai, a cardiovascular diseases researcher at the Academic Medical Center in Amsterdam.
In a second adjusted analysis that divided anticonvulsant drug use into agents that block sodium channels and those that don't, the sudden death cases were 2.9-fold more likely to be on a sodium-channel blocking anticonvulsant, compared with controls, a statistically significant difference.
In contrast, the fraction of sudden death cases on treatment with an anticonvulsant that doesn't block sodium channels was not significantly different from the rate at which these drugs were used by the controls.
Dr. Bardai said that he and his associates had no financial disclosures.