Small Interfering RNA to Reduce Lipoprotein(a) in Cardiovascular Disease

Lipoprotein(a) is a presumed risk factor for atherosclerotic cardiovascular disease. Olpasiran is a small interfering RNA that reduces lipoprotein(a) synthesis in the liver.

We conducted a randomized, double-blind, placebo-controlled, dose-finding trial involving patients with established atherosclerotic cardiovascular disease and a lipoprotein(a) concentration of more than 150 nmol per liter. Patients were randomly assigned to receive one of four doses of olpasiran (10 mg every 12 weeks, 75 mg every 12 weeks, 225 mg every 12 weeks, or 225 mg every 24 weeks) or matching placebo, administered subcutaneously. The primary end point was the percent change in the lipoprotein(a) concentration from baseline to week 36 (reported as the placebo-adjusted mean percent change). Safety was also assessed.