An experimental drug called pelacarsen, developed by Novartis, failed to show any measurable impact on heart attack or stroke in a large clinical trial, results presented Saturday at an American Heart Association meeting and published in the New England Journal of Medicine show.

The drug did exactly what it was designed to do: it reduced Lp(a) levels by 78%, compared with a 13% reduction on placebo.

But that dramatic drop translated into zero decreases in stroke, heart attack, cardiovascular deaths or procedures to open blocked arteries, according to NBC News and NPR, both of which covered the announcement.

Expectations for pelacarsen were extraordinarily high because Lp(a) has long been considered a particularly lethal target.

Like LDL cholesterol, it drives plaque buildup in arteries, but it also promotes blood clots — and unlike LDL, levels are entirely genetic, so diet and exercise have no effect on them.

About 1 in 5 Americans have elevated Lp(a), according to the American Heart Association, and most never realize they are at risk. NBC News quoted Dr. Amanda Doran of Vanderbilt University Medical Center, one of nearly 800 trial sites, calling it a "slam dunk" that clearly was not.

Dr. Karol Watson of UCLA told NBC News she had "not seen a more shockingly neutral trial in a while."

Researchers offered several explanations, none confirmed. Watson suggested to NBC News that treatment may simply have come too late in life — participants averaged age 60 and were followed about five years, but Lp(a) is high from conception, so decades of arterial damage may already have been done.

NPR added other possibilities raised by experts: maybe Lp(a) is only a marker rather than a cause of heart disease, maybe only patients with much higher levels would benefit, or maybe pelacarsen itself lacks whatever property a successful drug would need.

Roger Blumenthal of Johns Hopkins told NPR that longer or earlier treatment might still work.

Despite the disappointment, experts interviewed by NBC News stressed that Lp(a) remains a valuable indicator of heart disease risk and that testing is still worthwhile.

Earlier this year, the American College of Cardiology and the American Heart Association released guidelines recommending that every adult have Lp(a) levels measured once, since the blood test needs no repetition — levels are fixed for life.

"None of that invalidates Lp(a) as a robust marker of cardiovascular disease risk," Dr. John Wilkins of Northwestern Medicine told NBC News, adding that identifying high-Lp(a) patients lets doctors pursue other proven prevention strategies.

Doran echoed that people with elevated levels should be aware of them to pursue aggressive prevention. The failure of one drug to deliver benefit does not erase decades of data showing that high Lp(a) predicts disease.

No further study of pelacarsen is planned, Nissen told NBC News, but the field is far from finished.

Similar Lp(a)-lowering drugs remain in trials: Eli Lilly's lepodisiran, Amgen's olpasiran and Silence Therapeutics' zerlasiran, all injections that block the liver's production of Lp(a) but use small interfering RNA rather than pelacarsen's antisense oligonucleotide approach, which may mean fewer side effects.

Eli Lilly is also testing an oral drug called muvalaplin, and CRISPR gene-editing designed to permanently switch off the Lp(a)-producing gene is in early development, NBC News reports.

Novartis, in a statement quoted by NPR, said the study "provides meaningful evidence" about the Lp(a)–heart disease relationship and may help inform future approaches. "The take-home message is the story's not over," Watson told NPR.

Doran remains hopeful: "We're going to get it in the end."