Treatment with alirocumab can reduce major adverse cardiovascular events (MACEs) and death in patients with polyvascular disease, according to a review published in Journal of the American College of Cardiology.
Researchers of this study sought to determine the influence of polyvascular disease on the risk for MACEs and death in patients with recent acute coronary syndrome and concomitant dyslipidemia, and whether treatment with alirocumab modified these risks.
The study was a planned subanalysis of the ODYSSEY OUTCOMES trial (ClinicalTrials.gov identifier: NCT01663402), which included 18,924 patients with acute coronary syndrome and a history of hospitalization within the last year for myocardial infarction or unstable angina. In the ODYSSEY OUTCOMES trial, patients were randomly assigned to receive alirocumab (75 mg subcutaneously every 2 weeks, n=9462) or matching placebo (n=9462), in addition to intensive statin therapy, and were followed for a median of 2.8 years.
For this planned subanalysis, patients were categorized based on the distribution of their vascular disease (monovascular disease, polyvascular disease in 2 vascular beds, and polyvascular disease in 3 vascular beds). Of the total cohort, 17,370 participants had monovascular coronary disease, 1405 had polyvascular disease in 2 beds (coronary and peripheral artery or cerebrovascular), and 149 had polyvascular disease in 3 beds (coronary, peripheral artery, and cerebrovascular). Primary end point was incidence of MACEs, which included coronary heart disease death, nonfatal myocardial infarction, fatal or nonfatal ischemic stroke, or unstable angina requiring hospitalization. The secondary end point was all-cause death.
MACEs occurred in 10% of patients with monovascular disease in the placebo group compared with 8.5% in the alirocumab group; in 23.7% of the placebo group with 2-bed polyvascular disease (coronary artery and peripheral artery disease) compared with 22.8% in alirocumab group; and in 39.7% of the 3-bed disease placebo group compared with 26.8% in the alirocumab group.
The absolute risk reduction (ARR) of MACEs for patients with monovascular disease receiving alirocumab was 1.4% (95% CI, 0.6-2.3), 1.9% (95% CI, -2.4 to 6.2) for 2-bed disease with alirocumab, and 13.0% (95% CI, -1.8 to 4.3) in 3-bed disease with alirocumab.
For the secondary end point of all-cause death, overall incidence of death in the placebo and alirocumab groups was 4.1% and 3.5%, respectively. The incidence of death in patients in the placebo group with 1-, 2-, or 3-bed vascular disease was 3.5%, 10.0%, and 21.8%, respectively. Corresponding ARR for all-cause death with alirocumab was 0.4% (95% CI, 0.1%-1.0%), 1.3% (95% CI, -1.8% to 4.3%), and 16.2% (95% CI, 5.5%-26.8%), with an interaction P =.002.
A limitation of the study was that a substantial number of participants categorized as having monovascular disease may have had additional undetected peripheral artery or cerebrovascular disease; however, classification used for the study is similar to decision making used in clinical practice for patient classification.
Study investigators suggest that patients with polyvascular disease and a recent acute coronary syndrome comprise an easily identifiable subgroup of patients who are at high risk of ensuing MACEs or death, and that inhibition of PCSK9 with alirocumab, added to high-intensity statin therapy, has the potential for large risk reduction benefits in this group of patients.
Disclosure: Several study authors declared affiliations with the pharmaceutical industry. Please see the original reference for a full list of authors’ disclosures.
Jukema JW, Szarek M, Zijlstra LE, et al; ODYSSEY OUTCOMES Committees and Investigators. Alirocumab in patients with polyvascular disease and recent acute coronary syndrome: ODYSSEY OUTCOMES trial [published online March 18, 2019]. J Am Coll Cardiol. doi: 10.1016/j.jacc.2019.03.013