AHA LP(a) PAD toolkit: Emerging Diagnosis and Management

PCSK9 Inhibitors reduce Lp(a) up to 30%17 Data from trials of monoclonal antibodies directed against PCSK9 demonstrated dramatic LDL-C lowering by an average of 50% to 60%, but also modest Lp(a) lowering of 25% to 30%.28 FOURIER trial: The PCSK9 inhibitor (PCSK9i) evolocumab lowered Lp(a) by a median of 27% at 48 weeks.14, 29 ODYSSEY OUTCOMES trial: 18,924 patients with recent acute coronary syndrome who were taking high-intensity statin demonstrated that the PCSK9i alirocumab reduced Lp(a) by 23% after 4 months.30 ORION-11 (inclisiran) trial:31 The placebo-corrected percentage reduction in Lp(a) levels from baseline to Day 540 was 28.5%. Lipoprotein Apheresis lowers Lp(a) acutely by 50-85%12 14 Approaches for Lowering Lp(a) FDA approved for patients with familial hypercholesterolemia who have ASCVD (such as MI, PAD, CVD) and LDL-C > 100 mg/dl on maximal tolerable drug and lifestyle therapy with or without Lp(a) > 60 mg/dl.12 Indirect evidence suggests that Lp(a) lowering with Lipoprotein Apheresis may be associated with decreased ASCVD risk.24 Results in improved circulation, pain level, and walking distance in those with elevated Lp(a) and severe PAD.25 May reduce CV events in FH patients with elevated Lp(a) ≥60 mg/dL. 26, 27 We currently lack definitive proof that specific pharmacological lowering of Lp(a) reduces adverse cardiovascular outcomes. Many clinicians have the secondary goal of lowering Lp(a) in addition to lowering LDL-C and Apolipoprotein B (ApoB) in high-risk patients, in particular, when recurrent ASCVD events occur despite aggressive LDL-C lowering.12

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