Abstract 4143937: Association Between Lipoprotein(a) Levels and Incident Complex Coronary Revascularization Procedures in the FOURIER Trial

Background: Elevated Lp(a) levels are associated with a higher risk of major adverse CV events. Whether elevated Lp(a) levels are associated with a higher risk of complex coronary revascularization procedures or modify the benefit of evolocumab remains unknown. Methods: The FOURIER trial randomized 27,564 pts with stable ASCVD on optimized statin therapy to evolocumab vs placebo (median f/u 2.2 yrs). The association between Lp(a) (≥125 nmol/L) and complex coronary revascularization procedures (complex PCI or any CABG) was assessed in pts from the placebo arm with an adjusted Cox regression model. Complex PCI events were identified through blinded review of all revascularization events and defined as ≥1 of: multivessel PCI, ≥3 stents, ≥3 lesions treated, bifurcation PCI, or total stent length >60 mm. Effect modification between Lp(a), evolocumab and the risk of complex revascularization was assessed by including an interaction term in the model. Kaplan-Meier event rates are reported at 3 yrs. Results: In FOURIER, 4048 (32%) pts had a baseline Lp(a) concentration ≥125 nmol/L. A total of 332 complex coronary revascularization procedures occurred. Pts with higher baseline Lp(a) levels were more frequently female (29% vs 23%) and more likely to have multivessel disease (24% vs 21%), diabetes mellitus (38% vs 34%) or prior PCI (66% vs 60%). Higher baseline Lp(a) was associated with a 27% higher risk of complex coronary revascularization (3.7% vs 3.2%; HRadj 1.27, 95% CI: 1.01-1.59; P=0.04) ( Fig 1A ), including a 41% higher risk of complex PCI (2.3% vs 1.7%; HRadj 1.41, 95% CI: 1.05-1.90). Evolocumab significantly reduced the risk of complex coronary revascularization procedures by 22% (HR 0.78, 95%CI [0.63, 0.95]) in pts with Lp(a) <125 nmol/L and by 41% (HR 0.59, 95%CI [0.45, 0.78]) in pts with Lp(a) ≥125 nmol/L ( Fig 1B ). Conclusion and Relevance: Among pts with ASCVD in FOURIER, higher baseline Lp(a) levels helped identify those with an increased risk of complex PCI or CABG. These findings highlight the value of baseline Lp(a) levels in identifying pts at risk for future complex coronary revascularization and the potential for reducing such high-risk and costly procedures with evolocumab. Clinical Trial Registration . NCT01764633