In ODYSSEY trial, the addition of PCSK9 inhibitor, Alirocumab to high-intensity statin further reduced cardiovascular events by 15% in patients with very-high baseline CVD risk (prior ACS) and elevated atherogenic cholesterol particles. Atherogenicity was defined by LDLc ≥70 mg/dL, non-HDLc ≥100 mg/dL, or Apo B ≥80 mg/dL.
About 19,000 patients with acute coronary syndrome 1-12 months prior to study initiation were followed for 3 years. The study target was final LDLc between 25-50 mg/dL. Similar to FOURIER 2017 results, ODYSSEY 2018 adds more evidence to the notion “the lower the LDLc, the lower ASCVD events”
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N E J M
Odyssey
November 2018
BACKGROUND
Patients who have had an acute coronary syndrome (ACS) are at high risk for recurrent ischemic cardiovascular events. We sought to determine whether alirocumab, a human monoclonal antibody to proprotein convertase subtilisin–kexin type 9 (PCSK9), would improve cardiovascular outcomes after an ACS in patients receiving high-intensity statin therapy.
METHODS
We conducted a multicenter, randomized, double-blind, placebo-controlled trial involving 18,924 patients who had:
- ACS 1-12 months earlier
- LDLc ≥70 mg/dL
- non-HDLc ≥100 mg/d, or
- Apo B ≥80 mg/dL
- Were receiving statin therapy at
- A composite primary endpoint event occurred in 903 patients (9.5%) in the alirocumab group and in 1052 patients (11.1%) in the placebo group (HR 0.85, p<0.001).
- A total of 334 patients (3.5%) in the alirocumab group and 392 patients (4.1%) in the placebo group died (HR, 0.85, p<0.05).
- The absolute benefit of Alirocumab with respect to the composite primary endpoint was greater among patients who had a baseline LDLc ≥100 mg/dL than among patients who had a lower baseline level.
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).
CONCLUSIONS
Among patients who had a previous ACS and who were receiving high-intensity statin therapy, the risk of recurrent ischemic CVEs was lower among those who received alirocumab than among those who received placebo.
- The dose of Alirocumab was adjusted under blinded conditions to target an LDLc 25-50 mg/dL.
Primary endpoint was a composite of death from coronary heart disease, nonfatal myocardial infarction, fatal or nonfatal ischemic stroke, or unstable angina requiring hospitalization.
RESULTS
The median duration of follow-up was 2.8 years.
- A composite primary endpoint event occurred in 903 patients (9.5%) in the alirocumab group and in 1052 patients (11.1%) in the placebo group (HR 0.85, p<0.001).
- A total of 334 patients (3.5%) in the alirocumab group and 392 patients (4.1%) in the placebo group died (HR, 0.85, p<0.05).
- The absolute benefit of Alirocumab with respect to the composite primary endpoint was greater among patients who had a baseline LDLc ≥100 mg/dL than among patients who had a lower baseline level.
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).
CONCLUSIONS
Among patients who had a previous ACS and who were receiving high-intensity statin therapy, the risk of recurrent ischemic CVEs was lower among those who received alirocumab than among those who received placebo.
- High-intensity dose or
- Maximum tolerated dose.
Patients were randomly assigned to receive Alirocumab subQ at a dose of 75 mg (9462 patients) or matching placebo (9462 patients) every 2 weeks.
- The dose of Alirocumab was adjusted under blinded conditions to target an LDLc 25-50 mg/dL.
Primary endpoint was a composite of death from coronary heart disease, nonfatal myocardial infarction, fatal or nonfatal ischemic stroke, or unstable angina requiring hospitalization.
RESULTS
The median duration of follow-up was 2.8 years.
- A composite primary endpoint event occurred in 903 patients (9.5%) in the alirocumab group and in 1052 patients (11.1%) in the placebo group (HR 0.85, p<0.001).
- A total of 334 patients (3.5%) in the alirocumab group and 392 patients (4.1%) in the placebo group died (HR, 0.85, p<0.05).
- The absolute benefit of Alirocumab with respect to the composite primary endpoint was greater among patients who had a baseline LDLc ≥100 mg/dL than among patients who had a lower baseline level.
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).
CONCLUSIONS
Among patients who had a previous ACS and who were receiving high-intensity statin therapy, the risk of recurrent ischemic CVEs was lower among those who received alirocumab than among those who received placebo.
