American College of Cardiology

American College of Cardiology

March 20, 2017
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Alirocumab lowers LDL in patients with, without atherosclerotic CVD

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WASHINGTON — LDL levels were “substantially reduced” in patients assigned alirocumab, regardless of whether they had atherosclerotic CVD, according to research presented at the American College of Cardiology Scientific Session.

“The phase 3 trials in ODYSSEY were designed to evaluate efficacy and safety in patients with and without [CVD],” Peter H. Jones, MD, associate professor of medicine, Center for Cardiovascular Disease Prevention, Methodist DeBakey Heart and Vascular Center, Baylor College of Medicine, Houston, said during the presentation. “Most of the trials in ODYSSEY were with patients who had established [CVD], about 70% of them. What we wanted to look at is that 30% without [CVD] and compare them to those with CVD and see if there [were] any potential differences in response, and safety or adverse events.”

Researchers analyzed 4,983 patients with hypercholesterolemia who participated in one of 10 phase 3 trials from the ODYSSEY clinical study program of alirocumab (Praluent, Sanofi/Regeneron).

Jones and colleagues pooled participants into four groups based on the dose of alirocumab in their study and whether they were assigned to ezetimibe (Zetia, Merck) or placebo as controls.

“Alirocumab can be given at 75 or 150 mg, but in Pool 1, everybody was randomized to 150 mg every 2 weeks or placebo,” Jones said in the presentation. “Most of the information in this entire analysis actually comes from Pool 1, which includes the Long-Term trial, which was 78 weeks in duration.”

“Pool 2, 3 and 4 was a titration with alirocumab,” Jones said. “Patients were randomized to 75 [mg] every 2 weeks, and could be increased to 150 mg if they had not achieved their goal in LDL. The goal for patients with atherosclerotic [CVD] was less than 70 mg/dL and those without [CVD] was less than 100, so it was [titratable] based on their LDL cholesterol at 12 weeks.”

Patients were stratified by whether they had atherosclerotic CVD; approximately 70% did. Those in three of the pools were taking background statins, of which 85% were taking the maximally tolerated dose. In pool 4, there was no background statin use.

The outcome of interest was effectiveness and safety of alirocumab in lowering lipid levels in patients with and without atherosclerotic CVD.

At 24 weeks, LDL percent reductions were comparable in those with or without clinical atherosclerotic CVD in pools 1 and 2, and LDL goal achievement was consistent among patients with or without atherosclerotic CVD assigned alirocumab in ezetimibe-controlled trials (pools 3 and 4), Jones and colleagues found.

Patients with atherosclerotic CVD who were assigned alirocumab (150 mg every other week; n = 1,208) had a 61.9% reduction in LDL levels (standard error = 0.8) while patients without atherosclerotic CVD assigned the same dose of alirocumab had a 55.7% reduction (standard error = 1.5; P for interaction = .2493).

At week 24, 80.6% of those with atherosclerotic CVD who received alirocumab (150 mg every other week) met their LDL goals compared with 73.9% of those without atherosclerotic CVD who received alirocumab (P for interaction = .7143).

“The goal attainment is equal in all four pools,” Jones said during the presentation. “Interestingly, the goal attainment looks lower in pool 4, but all patients were not on statins and had a 180 [mg/dL] as their baseline LDL, so the goal attainment of less than 70 [mg/dL] and less than 100 [mg/dL] was more challenging in pool 4.”

Treatment-emergent adverse events and study drug discontinuations were similar between those assigned alirocumab and those assigned ezetimibe or placebo regardless of atherosclerotic CVD status, Jones and colleagues found.

“In my personal opinion, if you look at Pool 1 where all patients started on 150 mg every 2 weeks, you get the maximum effect in both patient populations starting with that strategy without any safety concerns,” Jones said during the presentation. “I think that if you would like to get lower LDL cholesterol, I would use 150 mg from the beginning and don’t go through that titration step. If a patient is primary prevention, you might consider 75 [mg] and see if they need to go to 150 mg. Finally, I like the idea that if I start at 150 mg and I think I got too low on LDL, you have the option of backtitration to 75 [mg].” – by Darlene Dobkowski

Reference:

Jones P, et al. Abstract 1133M-03. Presented at: American College of Cardiology Scientific Session; March 17-19, 2017; Washington, D.C.

Disclosure: Jones reports receiving consultant fees and honoraria from Amgen, Merck and Sanofi/Regeneron.