Alirocumab may reduce stroke risk without increasing odds of hemorrhage
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New data from the ODYSSEY Outcomes trial show that alirocumab is effective at reducing risk for any stroke without increasing risk for hemorrhagic stroke.
In a cohort of 18,924 patients with recent ACS and elevated LDL despite intensive statin therapy, alirocumab (Praluent, Sanofi/Regeneron) was effective in reducing the risk for any stroke (HR = 0.72; 95% CI, 0.57-0.91) and ischemic stroke (HR = 0.73; 95% CI, 0.57-0.93), compared with placebo, during a follow-up of 2.8 years. According to the study, these effects were achieved without increasing the patients’ risk for hemorrhagic stroke (HR = 0.83; 95% CI, 0.42-1.65).
Moreover, researchers noted that the effect of alirocumab on stroke appeared greater for patients with higher baseline LDL but found no formal evidence of heterogeneity (P for interaction = .31).
“This analysis of the ODYSSEY Outcomes trial shows that in patients with recent ACS and dyslipidemia despite intensive statin therapy, the PCSK9 inhibitor alirocumab decreased the risk of stroke, irrespective of baseline LDL and of history of cerebrovascular disease, over a median follow-up of 2.8 years,” J. Wouter Jukema, MD, PhD, professor of cardiology in the department of cardiology at Leiden University Medical Center in the Netherlands, and colleagues wrote. “Furthermore, the present findings indicate that the risk of hemorrhagic stroke did not depend on achieved LDL levels in the alirocumab group.”
In other findings, the effect of alirocumab on stroke was similar among individuals with previous cerebrovascular disease and those without (P for interaction = .37).
Alirocumab effect on baseline LDL
In addition, researchers found no adverse relationship between lower achieved LDL and incidence of hemorrhagic stroke in the alirocumab group compared with placebo.
“The treatment effect appeared numerically greater with lower HRs for patients with higher baseline LDL, suggesting that patients with a higher risk at baseline have a larger benefit of alirocumab,” the researchers wrote. “However, this linear trend was not statistically significant.”
In this double-blind trial, researchers randomly assigned patients with ACS and elevated LDL to alirocumab or placebo, with target LDL levels of 25 mg/dL to 50 mg/dL, avoiding sustained levels below 15 mg/dL. Patients were randomly assigned to alirocumab or placebo 1 to 12 months after ACS. The aim of this analysis was to evaluate nonfatal, fatal ischemic or hemorrhagic stroke and stratified by baseline LDL level and prior cerebrovascular disease. As Healio previously reported, in the main results of ODYSSEY Outcomes, alirocumab reduced risk for major adverse CV events by 15% compared with placebo in this population.
Reassuring findings
“The ODYSSEY Outcomes trial findings are reassuring from a dose-response standpoint,” Cardiology Today Editorial Board Members Erin D. Michos, MD, MHS, director of women’s cardiovascular health at Johns Hopkins Ciccarone Center for the Prevention of Cardiovascular Disease, and Seth S. Martin, MD, MHS, director of the advanced lipid disorders program at the Ciccarone center, wrote in a related editorial. “If the hypothesis is that low LDL level increases hemorrhage stroke risk, then one would expect the signal to become stronger in PCSK9 inhibitor trials, where the LDL has been driven lower than in prior statin trials. Yet, now we have data from the FOURIER trial and the ODYSSEY Outcomes trial that do not exhibit any dose-response connection. This evidence is not only reassuring with respect to use of PCSK9 inhibitors but also from a mechanistic standpoint as it points away from the causal connection between low LDL and hemorrhagic stroke.” – by Scott Buzby
Disclosures: Jukema reports he received research support from Amgen, Astellas, AstraZeneca, Daiichi Sankyo, Eli Lilly, Merck/Schering-Plough, Pfizer, Roche and Sanofi. Please see the full study for all other authors’ relevant financial disclosures. Michos reports no relevant financial disclosures. Martin reports he received personal fees for serving on scientific advisory boards for Akcea Therapeutics, Amgen, Esperion, Novo Nordisk, Quest Diagnostics, Regeneron and Sanofi and is a co-inventor on a pending patent filed by The Johns Hopkins University for a system of LDL estimation.
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