Lp(a)-lowering drug failed to protect the heart in a large trial
A drug that dramatically lowered a well-known cardiovascular risk factor did not protect the heart. The results cast doubt on a promising strategy in cardiology.
Lipoprotein(a), shortened to Lp(a), is a blood particle made up of fats and proteins. At high levels it raises the risk of heart attack and stroke. About one in five people have genetically elevated Lp(a). That makes it an attractive drug target.
In the HORIZON trial, Novartis tested the drug pelacarsen in patients with established high cardiovascular risk. The study was large and rigorously designed, with a follow-up of nearly five years. Pelacarsen substantially lowered Lp(a) levels. But the HORIZON trial showed no difference in heart attacks, strokes, urgent procedures to restore blood flow to the heart, or deaths between participants who were assigned to take the drug or a placebo.
What this means for the field
The results were presented at the American Heart Association’s scientific sessions and simultaneously published in the New England Journal of Medicine. Cardiologists are divided. Some say Lp(a) as a risk factor needs to be reassessed. Others argue the patient population should have been selected differently, or that the dose or duration of treatment was not optimal.
Lowering Lp(a) did not automatically lead to better cardiac outcomes. Whether that is due to the drug itself, the patient group, or the way Lp(a) causes harm remains unresolved after this trial. Other Lp(a)-targeting drugs are still being investigated.
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