DENVER – Both the second-generation as well as the first-generation antipsychotic agents proved independently associated with greater than threefold increased risks of sudden cardiac death, according to results from a large, population-based study.
However, schizophrenia per se was not linked to an increased risk, Dr. Audrey Uy-Evanado reported at the annual meeting of the Heart Rhythm Society.
She presented data from the ongoing landmark Oregon Sudden Unexplained Death Study involving 1,544 documented sudden cardiac deaths (SCDs) and 774 matched controls.
The prevalence of diagnosed schizophrenia among patients with SCD was 2.5%, significantly greater than the 0.5% figure in controls. At the time of SCD, 8.2% of subjects were on an antipsychotic agent, compared with 1.9% of controls.
Second-generation, or "atypical," antipsychotic agents such as risperidone (Risperdal) and olanzapine (Zyprexa) were being used by 6.3% of the SCD cohort and 1.3% of controls. First-generation antipsychotic agents such as haloperidol, fluphenazine, and chlorpromazine were used by 2.6% of the SCD group, compared with 0.5% of controls. All of these between-group differences were highly significant.
Third-generation antipsychotic agents such as aripiprazole (Abilify) were so rarely used – only 0.1% of patients were on a third-generation agent – that it wasn’t possible to draw any conclusions about SCD risk, according to Dr. Uy-Evanado of Cedars-Sinai Medical Center in Los Angeles.
In terms of cardiovascular risk factors, hypertension and obesity were significantly more prevalent in the control group – but the SCD cohort had increased rates of diabetes, chronic kidney disease, and severe left ventricular dysfunction.
Aside from schizophrenia, rates of other psychiatric disorders didn’t differ between the two groups.
In a multivariate logistic regression analysis adjusted for age, gender, and comorbidities, having schizophrenia was not associated with an increased risk of SCD. However, patients on a first-generation antipsychotic agent had a 3.76-fold increased risk of SCD (P = .0002), and those on a second-generation antipsychotic drug had a 3.3-fold increased risk.
This study was undertaken as a follow-up to an earlier report from the Oregon Sudden Unexplained Death Study, which broadly identified antipsychotic drug therapy as being associated with SCD. That observation raised the question as to whether the risk is limited to specific classes of antipsychotic agents. The answer appears to be no.
The Oregon Sudden Unexplained Death Study is funded by Oregon Health and Science University and the Centers for Disease Control and Prevention. Dr. Uy-Evanado reported having no conflicts of interest.