Abstract 10291: Elevated C-Reactive Protein Level Amplifies the Association of Lipoprotein(a) With Cardiovascular Risk and Risk Reduction With Alirocumab After Acute Coronary Syndrome

Circulation, vol. 146

Abstract

Background: In the ODYSSEY OUTCOMES trial (NCT01663402) the PCSK9 inhibitor alirocumab [ALI] reduced the risk of cardiovascular events [CVE] after acute coronary syndrome [ACS] in patients [pts] with elevated atherogenic lipoproteins despite optimized statin treatment, an effect modified by baseline levels of lipoprotein [Lp](a). Levels of the inflammatory biomarker high-sensitivity C-reactive protein [hsCRP] are associated with risk after ACS. In this post hoc analysis, we determined whether Lp(a)-associated risk of CVE after ACS and reduction in that risk with ALI are modified by concurrent hsCRP levels. Methods: 18,924 pts were randomized to ALI or placebo [PBO] 1-12 months after ACS and followed for median 2.8 years. Baseline Lp(a) and hsCRP were available in 18,290 pts. CVE [CV death, non-fatal MI, stroke, unstable angina or heart failure hospitalization, ischemia-driven coronary revascularization, peripheral artery events, and venous thromboembolism] were evaluated by baseline quartile of Lp(a) and by hsCRP dichotomized at 0.2 mg/dL. Results: Median (Q1-Q3) baseline Lp(a) was 21.3 (6.7-59.6) mg/dL. In 10,323 pts with baseline hsCRP<0.2 mg/dL ( Fig top ) risk of CVE in the PBO group increased modestly in Lp(a) Q4 (P trend =0.0592). Overall treatment hazard ratio [HR] was 0.91 without significant trend across Lp(a) quartiles. In 7967 pts with baseline hsCRP≥0.2 mg/dL ( Fig bottom ) risk of CVE in the PBO group was elevated and increased across Lp(a) quartiles (P trend <0.0001). Overall treatment HR was 0.82 and decreased across Lp(a) quartiles (P trend =0.0003). Conclusion: Elevated hsCRP amplifies the relationship of Lp(a) with risk of CVE after ACS and the reduction in that risk with alirocumab. Funding: Sanofi, Regeneron Pharmaceuticals

Authors 14

1. Gregory G. Schwartz

   University of Colorado Anschutz

   Affiliation as printed

   Div of Cardiology, Univ of Colorado Sch of Medicine, Aurora, CO

2. Michael J. Szarek

   SUNY Downstate Health Sciences University

   Affiliation as printed

   SUNY Downstate Sch of Public Health, Brooklyn, NY

3. Deepak L. Bhatt

   Brigham and Women's Hospital

   Affiliation as printed

   Brigham and Womens Hosp, Boston, MA

4. Vera Bittner

   University of Alabama at Birmingham

   Affiliation as printed

   Univ of Alabama Birmingham, Birmingham, AL

5. Rafael Díaz

   Estudios Clínicos Latinoamérica

   Affiliation as printed

   ECLA International, Rosario, Argentina

6. Genevive Garon

   Sanofi (Canada)

   Affiliation as printed

   Sanofi Canada, Laval, Canada

7. Shaun G. Goodman

   St. Michael's Hospital · University of Toronto

   Affiliation as printed

   St Michael's Hosp, Univ of Toronto, Toronto, Canada

8. Robert A. Harrington

   Stanford University

   Affiliation as printed

   Stanford Univ, Stanford, CA

9. J. Wouter Jukema Aachen Leiden Univ. Med. Ctr

   Leiden University · Leiden University Medical Center

   Affiliation as printed

   Leiden Univ Med Ctr, Leiden

10. Garen Z. Manvelian

    Regeneron (United States)

    Affiliation as printed

    Regeneron, Tarrytown, NY

11. Robert C. Pordy

    Regeneron (United States)

    Affiliation as printed

    Regeneron Pharmaceuticals, Tarrytown, NY

12. Harvey Douglas White

    Auckland City Hospital

    Affiliation as printed

    Auckland City Hosp, Auckland

13. Andreas Michael Zeiher

    Goethe University Frankfurt · University Hospital Frankfurt

    Affiliation as printed

    Klinikum d. J. W Goethe-Universitat, Frankfurt

14. Philippe Gabríel Steg

    Hôpital Bichat-Claude-Bernard

    Affiliation as printed

    Hopital Bichat, Paris, France