ODYSSEY OUTCOMES: Addition of PCSK9i to Background Statin Therapy Further Reduces MACE

Study Design¹

    *1-12 months from index ACS event

    **Blinded adjustment of alirocumab dose to target achieved LDL-C 25- 50 mg/dl and avoid sustained levels <15 mg/dl

    aPrimary efficacy endpoint (a composite of death from CHD, nonfatal MI, fatal or nonfatal ischaemic stroke, or unstable angina requiring hospitalization)

    HDL-C, High-density lipoprotein cholesterol; Q2W, every 2 weeks; SC, subcutaneous

Major Primary endpoints¹

The primary endpoint was a composite of:

  • Death from coronary heart disease
  • Nonfatal myocardial infarction
  • Fatal or nonfatal ischemic stroke
  • Unstable angina requiring hospitalization.

Major Secondary efficacy Endpoints²

Tested in the following hierarchical sequence:

  • CHD event: CHD death, nonfatal MI, unstable angina requiring hospitalization, or ischaemia-driven coronary revascularization*
  • Major CHD event: CHD death or nonfatal MI
  • CV event: CV death, nonfatal CHD event, or nonfatal ischaemic stroke
  • All-cause death, nonfatal MI, nonfatal ischaemic stroke
  • CHD death
  • CV death
  • All-cause death

*Revascularization performed because of recurrent ACS, new or progressive symptoms of myocardial ischemia or new or progressive abnormalities on functional testing, except revascularization due to restenosis at a prior coronary intervention site.

ODYSSEY OUTCOMES: Addition of PCSK9i to Background Statin Therapy Further Reduces MACE

Safety: Incidence or adverse events and laboratory abnormalities was similar in the alirocumab group and the placebo group, apart from local injection-site reaction (3.8% in alirocumab group vs 2.1% in the placebo group, p<0.001).

ᵃ Primary efficacy endpoint (a composite of death from CHD, nonfatal MI, fatal or nonfatal ischaemic stroke, or unstable angina requiring hospitalization)

CHD, Coronary Heart Disease; CI, Confidence Interval; MI, Myocardial Infarction

Primary MACE, All-Cause Death and Safety

Safety

Similar incidence of adverse events and laboratory abnormalities in the alirocumab group and the placebo group, except for local injection-site reactions (3 .8% in the alirocumab group vs 2.1% in the placebo group, p<0.001)¹

*Nominal p-value; ᵃBased on cumulative incidence; bp-interaction value for ARR <0.001 in post-hoc analysis

ARR, Absolute Risk Ratio; HR, Hazard ratio

All-Cause Death⁴

*Nominal p-value

†Based on cumulative incidence

Primary Analysis Conclusions¹

  • The primary results show that, compared with placebo in patients with recent ACS, alirocumab 75 or 150 mg SC twice a week targeting LDL-C levels 25-50 mg/dl reduced MACE, MI*, ischemic stroke* and was associated with a lower rate of all-cause death
  • Among patients with ACS and baseline LDL-C >100 mg/dl, alirocumab was well tolerated, reduced MACE by 24% (absolute risk reduction [ARR] 3.4%), and was associated with a lower rate of all-cause death compared with placebo

*Nominally significant as per hierarchical testing.

    1. Shwartz GG, et al. NEJM. 2018; 397:2097-107
    2. Shwartz GG, et al. Am Heart J. 2014; 168:682-689.e1
    3. Steg PG, et al. Circulation. 2019; 140(2):103-12
    4. Shwartz GG, et al. NEJM. 2018; 397:2097-107.Supplementary Appendix
VIEW PUBLISHED ARTICLE

MAT-BH-2100509/v2/Jun 2023