TCT-423 Long-Term Proprotein Convertase Subtilisin/Kexin Type 9 Inhibition With Evolocumab and Aortic Stenosis Events: An Analysis from FOURIER and FOURIER-OLE

Background: Evolocumab is associated with a lower risk of aortic stenosis (AS) events in patients with ASCVD. Whether this association persists in the long term remains unknown. Methods: In FOURIER, 27,564 patients w/ stable ASCVD were randomized to evolocumab vs placebo (median f/u 2.2 yrs). In FOURIER‐OLE, 6,635 patients from FOURIER were transitioned to open‐label evolocumab (additional median f/u 5 years). Site‐reported new AS, worsening AS, or AVR were analyzed as AS events. Associations between achieved (12 week) Lp(a) and LDL‐C levels and risk of AS events were adjusted for age, sex, DM, HTN, smoking, eGFR, and achieved LDL‐C or Lp(a). Risk of AS events was calculated according to original randomized tx arm for the overall period, first year, and then beyond the first year. Results: A total of 120 patients experienced AS events over a median of 7.1 years. Higher achieved Lp(a) levels were associated with greater risk of AS events (Q4 vs Q1: HRadj: 2.50; 95% CI.: 1.38‐4.50), as were higher achieved LDL‐C levels (Q4 vs Q1: HRadj: 1.81; 1.01‐3.27). The hazard ratio for AS events with original randomization to evolocumab vs placebo was 0.75 (95% CI.: 0.53‐1.08). In the first year the HR was 1.09 (95% CI.: 0.48‐2.47); beyond the first year the HR was 0.68 (0.45‐1.01) (Figure 1). [Formula presented] Conclusion: In patients with ASCVD, higher achieved Lp(a) and LDL‐C levels were associated with higher rates of AS events in the long‐term. The risk of AS events tended to be lower with initial randomization to evolocumab, especially after the first year. Categories:

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Valvular Disease: Aortic