An epilepsy drug that inhibits the histone deacetylase 9 (HDAC9) gene was associated with a significantly reduced risk of recurrent stroke in a pooled cohort study of nearly 12,000 patients.

Compared to all participants not taking sodium valproate (SVA), those prescribed the antiepileptic medication demonstrated a 53 percent reduced risk of recurrent stroke. When comparing those on SVA versus other antiepileptic drugs, a 56 percent reduced risk was observed, lead researcher Rebecca L. Brookes, PhD, and colleagues reported in Stroke.

“Although the design of our study is prone to systematic and random error and cannot infer causality, the results provide some evidence for the pre-study hypothesis and suggest that SVA, a nonspecific HDAC inhibitor, may be associated with a reduced stroke recurrence rate,” the researchers wrote.

Brookes et al. arrived at that hypothesis because previous studies have demonstrated mice with a deficiency of the HDAC9 gene show decreased aortic atherosclerosis. Because SVA inhibits the same gene, the researchers predicted it could have value as a secondary preventive measure against stroke.

“Previously, data have suggested that SVA reduces stroke risk in a stroke-free population, but this analysis provides new data suggesting that such an effect can also be found in patients who have already presented with ischemic stroke,” they wrote.

Brookes and colleagues analyzed data from three prospective studies of patients with a previous stroke or transient ischemic attack. The pooled cohort included 11,949 patients and average follow-up of the studies ranged from 3.4 to 4.6 years.

In all, there were 17 recurrent strokes in 168 patients prescribed SVA at any point during study follow-up compared to 105 recurrent strokes in 530 patients taking other antiepileptic drugs.

The researchers didn’t have precise dates for when patients began taking medications, so they set the start date as the first follow-up appointment in which they reported taking the drugs. Another limitation is there wasn’t enough data to assess the effects of different doses.

Still, the relationship between SVA and reduced stroke risk warrants further investigation in randomized controlled trials of the drug versus other HDAC9 inhibitors, Brookes and colleagues suggested.

“SVA is a nonspecific HDAC inhibitor (inhibiting a wide range of HDACs) and has other actions, independent of HDAC9 inhibition,” they wrote. “Hence, a more specific inhibitor of HDAC9 might have a stronger effect in reducing the risk of recurrent stroke.”