Pelacarsen Lowers Lp(a) but Fails to Cut Heart Risks

The Horizon trial found no reduction in heart attacks, strokes, cardiovascular deaths or procedures to restore blood flow among people taking pelacarsen, compared with those given a placebo. The findings were discussed on November 7 during a research meeting hosted by the American Heart Association and appeared in the New England Journal of Medicine.

The study enrolled 8,322 people with elevated Lp(a) who had experienced a heart attack, stroke or another heart problem in the preceding decade. Participants were followed for an average of nearly five years. Pelacarsen lowered Lp(a) levels by 78%, while levels in the placebo group fell 13%, but the difference did not translate into fewer serious cardiovascular events.

Lp(a) is largely determined by genetics and can contribute to artery-clogging plaque and blood clots. About one in five Americans has high levels. Researchers said the neutral result was unexpected, though they suggested treatment may have begun too late to change risks accumulated over a lifetime. Participants also received intensive care to control factors such as LDL cholesterol and blood pressure.

The trial’s findings do not erase Lp(a)’s value as a risk indicator, cardiologists said. Recent guidelines from the American College of Cardiology and American Heart Association recommend that adults have their levels checked once. Doctors can use the result to identify people who may benefit from other preventive measures.

No further pelacarsen study is planned, trial leader Steven Nissen said. Other Lp(a)-lowering drugs are being tested, but their ability to prevent heart problems remains unproven. Eli Lilly is also studying an oral treatment, muvalaplin.