**An experimental drug that sharply lowered levels of an inherited form of cholesterol failed to protect patients from heart attacks and strokes, leaving researchers searching for answers.
Novartis’ pelacarsen reduced lipoprotein(a), or Lp(a), by 78% in the Phase 3 Horizon trial. The study included 8,322 people with elevated Lp(a) and a history of heart attack, stroke or another heart problem. Despite the reduction, the drug did not lower the risk of major cardiovascular events compared with a placebo, NBC News reports. Researchers presented the findings at the American Heart Association’s Scientific Sessions and published them in The New England Journal of Medicine.
“I really thought that this was going to be a slam dunk,” Dr. Amanda Doran, a Vanderbilt cardiologist, told NBC News. “We were pretty invested, so it obviously hurts.”
Lp(a) contributes to plaque buildup in arteries and can help form blood clots. Unlike LDL, often called bad cholesterol, Lp(a) levels are largely determined by genetics rather than diet or exercise. About one in five Americans has elevated levels, according to the American Heart Association.
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Still, experts say testing remains important. New American College of Cardiology and American Heart Association guidelines recommend that every adult have their Lp(a) measured at least once.
“None of that invalidates Lp(a) as a robust marker of cardiovascular disease risk,” Dr. John Wilkins of Northwestern Medicine said. He noted that identifying elevated levels can help doctors pursue other prevention strategies.
Dr. Karol Watson of UCLA suggested participants may have started treatment too late, after years of exposure to high Lp(a). The average participant was 60, and follow-up lasted about five years. Aggressive treatment of LDL and blood pressure, along with aspirin use, may also have reduced the remaining risk.
Novartis is ending development of pelacarsen, according to Dr. Steven Nissen, who led the trial. Eli Lilly, Amgen and Silence Therapeutics are testing other Lp(a) treatments, but none has yet been shown to prevent heart attacks or strokes.
“We’re going to get it in the end,” Doran said.
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