Alirocumab Improves Outcomes Post-ACS: ODYSSEY OUTCOMES Published

Debra L Beck

November 09, 2018

The proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor alirocumab (Praluent, Sanofi/Regeneron) was superior to placebo for the reduction of ischemic cardiovascular events in patients with a history of acute coronary syndrome (ACS) already receiving high-intensity statin therapy, just-published results from the ODYSSEY OUTCOMES trial show.

Gregory G. Schwartz, MD, PhD, from the University of Colorado School of Medicine, Aurora, confirmed in an email exchange with | Medscape Cardiology that the data published online November 7 in the New England Journal of Medicine are essentially those presented at the American College of Cardiology (ACC) 2018 Annual Scientific Session in March.

"They show that there was a 15% reduction in MACE with alirocumab, 15% fewer deaths with alirocumab than with placebo, that the benefits of alirocumab were more pronounced among patients whose baseline low-density-lipoprotein cholesterol [LDL-C] was at least 100 mg/dL, that there were no safety concerns with alirocumab, and that there was a modest excess of injection site reactions that were usually mild."

The trial's findings were covered in detail by | Medscape Cardiology when they were presented at the ACC meeting.

In short, ODYSSEY OUTCOMES involved 18,924 patients who had experienced an ACS 1 to 12 months earlier, a LDL-C of at least 70 mg/dL (1.8 mmol/L), and who were receiving a high-intensity statin or the maximum tolerated dose. Eligible participants also had to have a non-high-density-lipoprotein cholesterol level of at least 100 mg/dL (2.6 mmol/L), or an apolipoprotein B level of at least 80 mg/dL.

Alirocumab 75 mg or matching placebo was administered subcutaneous every 2 weeks, with the dose of alirocumab adjusted under blinded conditions to target an LDL-C of 25 to 50 mg/dL (0.6 to 1.3 mmol/L).

Over 2.8 years of follow-up, the primary end point — a composite of death from coronary heart disease, nonfatal myocardial infarction, fatal or nonfatal ischemic stroke, and unstable angina requiring hospitalization — occurred in 9.5% of alirocumab-treated patients and 11.1% of placebo patients (hazard ratio, 0.85; P < .001).

The greatest benefit from alirocumab was seen in those with baseline LDL-C of at least 100 mg/dL, compared with those with lower LDL-C levels (P < .001 for the interaction between treatment and baseline LDL-C level).

ODYSSEY OUTCOMES is the second trial to show a reduction in hard events with a PCSK9 inhibitor, following the FOURIER trial findings reported at the 2017 ACC meeting.

The publication comes during a busy time. Just a few weeks ago, Amgen announced plans to cut the price on its PCSK9 inhibitor evolocumab (Repatha). In the spring, Sanofi/Regeneron Pharma made a similar commitment to cut the price of alirocumab and improve patient access.

Also, in a few days' time, attendees of the American Heart Association (AHA) Scientific Sessions in Chicago will hear three presentations of new data from ODYSSEY OUTCOMES, including an analysis of the economic implications of the trial and data on prevention of total (first and recurrent) events with alirocumab.

Schwartz noted that the timing of the publication was dictated by the review process and was not intentionally related to the upcoming AHA meeting.

AHA attendees will also hear about the new AHA lipid guidelines, which will, for the first time, include recommendations on when and for whom to use the new PCSK9 inhibitors.

The study was funded by Sanofi and Regeneron Pharmaceuticals. Schwartz reported grants from Sanofi during the conduct of the study, as well as grants from Cerenis, Resverlogix, Roche, and The Medicine Company.

N Engl J Med. Published online November 7, 2018. Article



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