A small interfering RNA, olpasiran was effective for significantly reducing the hepatic synthesis of lipoprotein(a) in patients with established atherosclerotic cardiovascular disease (CVD), a dose-finding study shows. With lipoprotein(a) a presumed risk factor for CVD, the results justify “longer and larger trials,” the authors conclude.
The randomized, double-blind, placebo-controlled trial included 281 patients with baseline lipoprotein(a) levels of 260.3 nmol/L and LDL cholesterol of 67.5 mg/dL. Olpasiran was administered subcutaneously in 1 of 4 doses (10, 75, or 225 mg every 12 weeks, or 225 mg every 24 weeks).
“At baseline, 88% of the patients were taking statin therapy, 52% were taking ezetimibe, and 23% were taking a proprotein convertase subtilisin–kexin type 9 (PCSK9) inhibitor,” the investigators report. “At 36 weeks, the lipoprotein(a) concentration had increased by a mean of 3.6% in the placebo group, whereas olpasiran therapy had significantly and substantially reduced the lipoprotein(a) concentration in a dose-dependent manner, resulting in placebo-adjusted mean percent changes of −70.5% with the 10-mg dose, −97.4% with the 75-mg dose, −101.1% with the 225-mg dose administered every 12 weeks, and −100.5% with the 225-mg dose administered every 24 weeks (P <0.001 for all comparisons with baseline). The overall incidence of adverse events was similar across the trial groups. The most common olpasiran-related adverse events were injection-site reactions, primarily pain.”