AHA 2018 – Chicago, IL, VS

Alirocumab was associated with fewer deaths from any cause among patients who had previously experienced an MI or unstable angina, and this was enhanced in patients who were followed for at least 3 years and those who had an LDL-c of ≥100 mg/dL at baseline. Moreover, additional new analyses showed an association between reduced non-fatal cardiovascular (CV) events and reduction in non-CV death during the trial period.

In the trial, alirocumab added to maximally-tolerated statins was compared to maximally-tolerated statins alone in patients who had experienced an ACS within the last 12 months. Data published in The New England Journal of Medicine last week found alirocumab significantly reduced the risk of major adverse cardiovascular events (MACE) and was associated with a lower risk of death from any cause.

In pre-specified analyses of 8,242 patients followed for at least 3 years, alirocumab was associated with a 22% lower risk of death from any cause (HR: 0.78, 95%CI: 0.65-0.94, P-nominal=0.01). Separate post-hoc analyses showed that alirocumab-treated patients whose baseline LDL-c levels were ≥100 mg/dL experienced a 29% lower risk of death from any cause (HR: 0.71, 95%CI: 0.56-0.90).

In additional post-hoc analyses researchers found alirocumab-treated patients experienced fewer non-fatal CV events and were less likely to die from a non-CV event and that these two findings may be associated (association between non-fatal and fatal events HR: 2.35, 95%CI: 1.98-2.73, P<0.0001).

No new safety signals were found in the analyses. In ODYSSEY OUTCOMES, the incidence of adverse events was similar in the two groups, with the exception of local injection-site reactions (3.8% in the alirocumab group vs. 2.1% in the placebo group).

ODYSSEY OUTCOMES (n=18,924) assessed the effect of alirocumab on the occurrence of major adverse cardiovascular events (MACE) in patients who had experienced an ACS between 1-12 months (median 2.6 months) before enrolling in the trial, and who were already on intensive or maximally-tolerated statin treatment. Patients were randomized to receive alirocumab (n=9,462) or placebo (n=9,462) and were assessed for a median of 2.8 years, with some patients being treated for up to five years. Approximately 90% of patients were on a high-intensity statin.

The trial was designed to maintain patients' LDL-c levels between 25-50 mg/dL, using two different doses of alirocumab (75 mg and 150 mg). Alirocumab-treated patients started the trial on 75 mg every 2 weeks and switched to 150 mg every 2 weeks if their LDL-c levels remained above 50 mg/dL (n=2,615). Some patients who switched to 150 mg switched back to 75 mg if their LDL-c fell below 25 mg/dL (n=805), and patients who experienced two consecutive LDL-c measurements below 15 mg/dL while on the 75 mg dose (n=730) stopped active alirocumab therapy for the remainder of the trial.

Source: Press release Sanofi, November 11, 2018