The ODYSSEY OUTCOMES trial met its primary endpoint, demonstrating that high-risk patients who received alirocumab (Praluent, Sanofi) on top of their maximally-tolerated statin dose experienced significantly fewer major adverse cardiovascular events (MACE) compared with those on statins alone. The results were presented at the 2018 American College of Cardiology (ACC) Scientific Session (10–12 March, Orlando, USA).
ODYSSEY OUTCOMES (n=18,924) assessed the effect of alirocumab on the occurrence of MACE in patients who had experienced an acute coronary syndrome between one and 12 months (median 2.6 months) before enrolling in the trial, and who were already on maximally-tolerated statins. All patients were randomised to receive alirocumab (n=9,462) or a placebo (n=9,462) and were treated for an average (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’ low density lipoprotein (LDL) cholesterol levels between 25mg/dL and 50 mg/dL, using two different doses of alirocumab (75mg and 150mg). Alirocumab-treated patients started the trial on 75mg every two weeks, and switched to 150mg every two weeks if their LDL cholesterol levels remained above 50mg/dL (n=2,615). Some patients who switched to 150mg switched back to 75mg if their LDL cholesterol fell below 25mg/dL (n=805) and patients who experienced two consecutive LDL-cholesterol measurements below 15mg/dL while on the 75mg dose (n=730) stopped active alirocumab therapy for the remainder of the trial.
The key findings of the study were:
- On the primary endpoint, alirocumab reduced the overall risk of major adverse cardiac events (MACE) by 15% (HR=0.85, CI: 0.78-0.93; p=0.0003). The MACE composite endpoint includes patients who experienced a heart attack, ischemic stroke, death from coronary heart disease or unstable angina requiring hospitalisation
- Alirocumab was also associated with a lower risk of all-cause death overall (HR=0.85; CI: 0.73-0.98, nominal p=0.026)
According to a press release, a more pronounced effect observed in patients with baseline low density lipoprotein (LDL) cholesterol levels at or above 100 mg/dL, despite maximally-tolerated statins, who are at high risk of suffering a future event; in this group, alirocumab reduced risk of major adverse cardiovascular events by 24% and was associated with a 29% lower risk of death overall.
In this 18,924-patient, long-term trial, the safety profile of alirocumab was consistent with previous trials and no new safety issues were observed. In a pre-specified analysis, patients with baseline LDL cholesterol levels at or above 100mg/dL experienced a more pronounced effect from alirocumab, reducing their risk of MACE by 24% (HR=0.76, CI: 0.65-0.87). In a post-hoc analysis of this group, alirocumab was associated with a lower risk of death from any cause by 29% (HR=0.71, CI: 0.56-0.90). Furthermore, data from ODYSSEY OUTCOMES showed alirocumab to have an acceptable safety profile; no new safety concerns were raised by the trial.
Kausik Ray (Imperial College London, London, UK) says: “There is a wealth of evidence to show the important role that reducing high levels of bad cholesterol plays in heart attack and stroke prevention, and the ODYSSEY OUTCOMES study data is some of the most promising we’ve seen in this area. These new results show, for the first time, that use of alirocumab to lower cholesterol can reduce heart attacks and stroke in high-risk patients.”