Lp(a)HORIZON

Presented in LBS.01 at AHA 2026 (Saturday 7 November) and published simultaneously in NEJM, with the extended analyses in NEJM Evidence. Lp(a)HORIZON randomised 8,350 patients (8,322 analysed; mean age 59.7, 27 percent women, median Lp(a) 235.8 nmol/L, median LDL 64.6 mg/dL, 77.6 percent on a high-intensity statin) with established cardiovascular disease and Lp(a) of 70 mg/dL or more at 797 sites in 42 countries to monthly subcutaneous pelacarsen 80 mg or placebo. At 12 months Lp(a) fell 78.4 percent versus 3.2 percent (difference 77.7 points, 95 percent CI 77.0 to 78.4; median 64.4 versus 233.4 nmol/L). Over a median 4.7 years the primary endpoint (cardiovascular death, non-fatal MI, non-fatal stroke, urgent coronary revascularisation) occurred in 511 of 4,157 (12.3 percent) on pelacarsen and 503 of 4,165 (12.1 percent) on placebo, HR 1.02 (0.90 to 1.15), P=0.76; in the prespecified subgroup with Lp(a) of 90 mg/dL or more 402 of 3,266 versus 403 of 3,274, HR 1.00 (0.87 to 1.15). Three-point MACE 10.2 versus 10.1 percent (HR 1.01), the coronary composite 9.4 versus 9.7 percent (HR 0.97), all-cause death 5.7 versus 5.9 percent (HR 0.98, 0.82 to 1.17). Serious adverse events 37.3 versus 41.1 percent; influenza-like reactions 31.9 versus 5.8 percent, injection-site reactions 25.6 versus 2.9 percent, discontinuation for adverse events 20.6 versus 7.5 percent, 19 adjudicated anaphylaxis cases versus none, premature discontinuation of the regimen 35.1 versus 18.3 percent. The first outcomes trial of targeted Lp(a) lowering is completely neutral; Nissen: "It didn't work." Keep measuring Lp(a); the olpasiran and lepodisiran trials continue.