Alirocumab in Patients With Polyvascular Disease and Recent Acute Coronary Syndrome: ODYSSEY OUTCOMES Trial
J Wouter Jukema1, Michael Szarek2, Laurien E Zijlstra1
1Department of Cardiology, Leiden University Medical Center, Leiden, The Netherlands.
Insights
Patients with polyvascular disease and acute coronary syndrome (ACS) face high risks. Alirocumab significantly reduced major adverse cardiovascular events (MACEs) and death in these high-risk patients, showing potential benefits.
Area of Science:
- Cardiology
- Vascular Medicine
- Pharmacology
Background:
- Patients with acute coronary syndrome (ACS) and non-coronary atherosclerosis have elevated risks of major adverse cardiovascular events (MACEs) and mortality.
- The effect of proprotein convertase subtilisin-kexin type 9 (PCSK9) inhibition on lipid levels in these patients remains unclear.
Purpose of the Study:
- To assess the influence of polyvascular disease on MACEs and death risks in patients with recent ACS and dyslipidemia.
- To determine if alirocumab modifies these risks in the studied patient population.
Main Methods:
- A pre-specified analysis of the ODYSSEY OUTCOMES trial involving patients randomized to alirocumab or placebo post-ACS.
- Primary endpoint: composite of coronary heart disease death, myocardial infarction, ischemic stroke, or unstable angina. Secondary endpoint: all-cause death.
Main Results:
- Polyvascular disease was associated with increased MACEs (10.0% to 39.7%) and death (3.5% to 21.8%) incidence with placebo.
- Alirocumab demonstrated absolute risk reductions in MACEs (1.4% to 13.0%) and death (0.4% to 16.2%) across different polyvascular disease severities.
Conclusions:
- Polyvascular disease significantly elevates MACEs and death risks in patients with recent ACS and dyslipidemia.
- Alirocumab offers substantial absolute risk reductions for MACEs and death, indicating a potential therapeutic benefit in this high-risk group.
Background:
Patients with acute coronary syndrome (ACS) and concomitant noncoronary atherosclerosis have a high risk of major adverse cardiovascular events (MACEs) and death. The impact of lipid lowering by proprotein convertase subtilisin-kexin type 9 inhibition in such patients is undetermined.
Objectives:
This pre-specified analysis from ODYSSEY OUTCOMES (Evaluation of Cardiovascular Outcomes After an Acute Coronary Syndrome During Treatment With Alirocumab) determined whether polyvascular disease influenced risks of MACEs and death and their modification by alirocumab in patients with recent ACS and dyslipidemia despite intensive statin therapy.
Methods:
Patients were randomized to alirocumab or placebo 1 to 12 months after ACS. The primary MACEs endpoint was the composite of coronary heart disease death, nonfatal myocardial infarction, fatal or nonfatal ischemic stroke, or unstable angina requiring hospitalization. All-cause death was a secondary endpoint.
Results:
Median follow-up was 2.8 years. Of 18,924 patients, 17,370 had monovascular (coronary) disease, 1,405 had polyvascular disease in 2 beds (coronary and peripheral artery or cerebrovascular), and 149 had polyvascular disease in 3 beds (coronary, peripheral artery, cerebrovascular). With placebo, the incidence of MACEs by respective vascular categories was 10.0%, 22.2%, and 39.7%. With alirocumab, the corresponding absolute risk reduction was 1.4% (95% confidence interval [CI]: 0.6% to 2.3%), 1.9% (95% CI: -2.4% to 6.2%), and 13.0% (95% CI: -2.0% to 28.0%). With placebo, the incidence of death by respective vascular categories was 3.5%, 10.0%, and 21.8%; the absolute risk reduction with alirocumab was 0.4% (95% CI: -0.1% to 1.0%), 1.3% (95% CI: -1.8% to 4.3%), and 16.2% (95% CI: 5.5% to 26.8%).
Conclusions:
In patients with recent ACS and dyslipidemia despite intensive statin therapy, polyvascular disease is associated with high risks of MACEs and death. The large absolute reductions in those risks with alirocumab are a potential benefit for these patients. (Evaluation of Cardiovascular Outcomes After an Acute Coronary Syndrome During Treatment With Alirocumab [ODYSSEY OUTCOMES]: NCT01663402).
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