Abstract Body (Do not enter title and authors here): Background: Elevated lipoprotein(a) [Lp(a)] is a presumed causal risk factor for coronary heart disease (CHD). Estimating the absolute CHD risk reduction with potential Lp(a) lowering using real-world data may help characterize the anticipated patient-level benefits for new therapies directed to Lp(a). Aim: Model the magnitude of absolute reduction in recurrent CHD events that may be achieved by lowering Lp(a) concentration among adults with established atherosclerotic cardiovascular disease (ASCVD). Methods: The absolute risk of recurrent CHD was estimated using pooled data on participants with ASCVD at the time of Lp(a) measurement (nmol/L) from three observational studies: Atherosclerosis Risk in Communities Study, Reasons for Geographic and Racial Differences in Stroke, and UK Biobank. Recurrent CHD included non-fatal myocardial infarction, coronary revascularization, and fatal CHD. The absolute risk reduction over 10 years was extrapolated from Madsen et al. (2020) who estimated lowering Lp(a) by 105 nmol/L would be associated with a 20% recurrent CHD absolute risk reduction (i.e., equivalent risk reduction to a 1 mmol/L reduction in low-density lipoprotein cholesterol over 5 years). Results: Among 20,165 participants (mean age: 62 years, 31% female, mean follow-up: 10 years), 24% had Lp(a) ≥125 nmol/L (median level: 192 nmol/L) and 11% had Lp(a) ≥200 nmol/L median level: 254 nmol/L). Projecting a 60% or 95% reduction in Lp(a) among those with Lp(a) ≥125 nmol/L or ≥200 nmol/L indicates the absolute recurrent CHD risk reduction would increase across greater magnitudes of Lp(a) lowering. Lp(a) lowering of 150 nmol/L, 180 nmol/L and 240 nmol/L would result in a 26%, 32% and 84% greater reduction of recurrent CHD events per 1,000 person years, respectively, compared with the event reduction for Lp(a) lowering of 115 nmol/L (Figure).
Conclusions: These modelled projections from observational data suggest greater lowering of Lp(a) concentration may result in larger absolute reduction in recurrent CHD risk among adults with established ASCVD.