ORLANDO—The combination of ezetimibe and simvastatin significantly reduces the risk of nonhemorrhagic stroke, compared with simvastatin alone, according to a new analysis of data from the IMPROVE-IT trial. Patients with prior history of stroke particularly benefit from this combination.
“We believe these data support the use of intensive lipid-lowering therapy, which includes ezetimibe to prevent ischemic stroke,” said Stephen D. Wiviott, MD, a specialist in cardiovascular medicine at Brigham and Women’s Hospital in Boston, at the American Heart Association Scientific Sessions 2015.
He and his colleagues performed a prespecified secondary analysis of data from IMPROVE-IT, a double-blind study in which 18,144 patients on background optimal medical management were randomized post–acute coronary syndrome to simvastatin and ezetimibe at 40 mg/day and 10 mg/day, respectively, or simvastatin alone at 40 mg/day. At a median of six years of follow-up, the primary composite cardiovascular outcome was significantly reduced by 6% in the dual-therapy group, compared with statin monotherapy, with a number needed to treat (NNT) of 50, as previously reported.
The impetus for the prespecified stroke analysis was that, until the IMPROVE-IT study, no LDL cholesterol-lowering therapy other than statins had ever been shown to protect against stroke. The Cholesterol Trialists’ Collaboration meta-analysis, which included approximately 173,000 participants, previously showed that statin therapy reduces ischemic stroke risk by 20% per 1 mmol/L of LDL lowering. Researchers sought to determine whether add-on ezetimibe could decrease stroke risk further.
Stroke occurred in 641 patients during follow-up. As adjudicated by independent neurologists, 82% of the strokes were nonhemorrhagic, 16% were hemorrhagic, and 2% were unknown. The 14% relative risk reduction in overall stroke with simvastatin and ezetimibe, compared with simvastatin alone, with rates of 4.2% versus 4.8%, was not statistically significant. A significant 21% reduction in nonhemorrhagic stroke was seen with dual therapy, where the incidence during follow-up was 3.4%, compared with 4.1% for simvastatin alone, but this effect was accompanied by a statistically nonsignificant absolute 0.2% increase in hemorrhagic stroke in the simvastatin-and-ezetimibe group.
The combination of simvastatin and ezetimibe provided a clear stroke-prevention benefit among the 1,071 participants with prior stroke or transient ischemic attack at baseline. Their rate of nonhemorrhagic stroke during follow-up was 10.2% with simvastatin and ezetimibe versus 18.8% with simvastatin alone. This result yielded a 40% relative risk reduction favoring dual lipid-lowering therapy and an NNT of about 20. The investigators saw no significant difference in rates of hemorrhagic stroke between the two treatment arms, noted Dr. Wiviott.
The stroke-prevention benefit achieved by adding ezetimibe to simvastatin was apparent regardless of patient age, gender, renal function, baseline LDL cholesterol level, or other prespecified subcategories.
—Bruce Jancin