Conference Coverage

AHA: Ezetimibe reduces ischemic stroke risk


 

AT THE AHA SCIENTIFIC SESSIONS

References

ORLANDO – The combination of ezetimibe/simvastatin significantly reduced the risk of nonhemorrhagic stroke compared with simvastatin alone, with a particularly striking benefit seen in patients with prior history of stroke, in a new analysis from the landmark IMPROVE-IT trial.

“We believe these data support the use of intensive lipid lowering therapy, which includes ezetimibe to prevent ischemic stroke,” Dr. Stephen D. Wiviott said in reporting the findings at the American Heart Association scientific sessions.

He presented a prespecified secondary analysis 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/ezetimibe at 40/10 mg/day (Vytorin) or simvastatin (Zocor) at 40 mg/day. At a median of 6 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 (N Engl J Med. 2015 Jun 18;372[25]:2387-97).

The impetus for the prespecified stroke analysis was that up until IMPROVE-IT, no LDL cholesterol–lowering therapy other than statins had ever been shown to protect against stroke. The Cholesterol Trialists’ Collaboration meta-analysis, involving roughly 173,000 subjects, previously showed that statin therapy reduces ischemic stroke risk by 20% per 1 mmol/L of LDL lowering (Lancet. 2012 Aug 11;380[9841]:581-90). The question was, could add-on ezetimibe decrease stroke risk even 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/ezetimibe compared with simvastatin, with rates of 4.2% versus 4.8%, just missed achieving statistical significance (P = .052). A significant 21% reduction in nonhemorrhagic strokes was seen with dual therapy, where the incidence during follow-up was 3.4%, compared with 4.1% with simvastatin alone, but this effect was dampened by a numeric albeit statistically nonsignificant absolute 0.2% increase in hemorrhagic strokes in the simvastatin/ezetimibe group.

Far more impressive was the stroke-prevention benefit of simvastatin/ezetimibe among the 1,071 subjects with prior stroke or TIA at baseline. Their nonhemorrhagic stroke rate during follow-up was 10.2% with simvastatin/ezetimibe versus 18.8% with simvastatin alone, for a 40% relative risk reduction favoring dual lipid-lowering therapy and an NNT of about 20. Again, there was no significant difference in hemorrhagic stroke between the two treatment arms, noted Dr. Wiviott of Brigham and Womens Hospital, Boston.

The stroke-prevention benefit achieved by adding ezetimibe to simvastatin was seen regardless of patient age, gender, renal function, baseline LDL cholesterol level, or other prespecified subcategories.

IMPROVE-IT was sponsored by Merck. Dr. Wiviott reported receiving research grants from Merck, AstraZeneca, and Eisai and serving as a consultant to nine pharmaceutical companies.

bjancin@frontlinemedcom.com

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