Experimental drug reduces little-known cholesterol that raises heart attack risk

Researchers have recently made a groundbreaking discovery of an experimental medication that has the potential to significantly reduce a cholesterol-like particle known as lipoprotein(a) or Lp(a). Elevated levels of Lp(a) can increase the risk of heart attacks and strokes, yet many Americans are unaware that this dangerous particle is circulating in their blood.

Unlike traditional cholesterol, lifestyle changes such as diet, exercise, and weight loss have no impact on Lp(a) levels. This has led to Lp(a) being referred to as “one of the last untreatable frontiers of cardiovascular risk” by experts at the Cleveland Clinic who led the study.

The experimental drug, lepodisiran, developed by Eli Lilly and funded by the study, has shown promising results in silencing the main gene responsible for synthesizing Lp(a). Similar experimental gene therapies with the same mechanism of action are also in development, according to Cleveland Clinic.

The results of the study, which were published in The New England Journal of Medicine and presented at the American College of Cardiology annual meeting, confirmed earlier findings that lepodisiran can effectively reduce Lp(a) levels in the blood.

Lipoprotein(a) is a risk factor for heart disease that is largely determined by genetics, rather than lifestyle factors. Approximately 20-25% of people worldwide have elevated levels of Lp(a), equating to around 64 million Americans and 1.4 billion people globally. Lp(a) is more prone to plaque buildup and clots in the arteries than LDL cholesterol, making it a significant risk factor for cardiovascular events.

The clinical trial involved 320 participants from various countries who were randomly assigned to receive either a placebo or one or two injections of lepodisiran. Participants who received the highest dose of the drug showed nearly 100% reduction in Lp(a) levels after six months, with those receiving a second dose maintaining this reduction at the one-year mark.

While the study demonstrated impressive results in reducing Lp(a) levels, experts noted that further research is needed to determine if this reduction translates into a lower risk of heart attacks and strokes. Safety concerns were minimal, with only mild reactions reported at the injection site by 12% of participants.

It is important to note that the study had limited representation of Black participants, who are more likely to have elevated Lp(a) concentrations than White individuals. To address this disparity, the researchers are enrolling more Black patients in their larger phase 3 clinical trial.

Overall, the findings of this research offer hope for the millions of individuals with elevated Lp(a) levels, as well as underscore the importance of checking Lp(a) levels in all adults. While traditional cholesterol levels may change over time, Lp(a) levels remain stable throughout life, making it essential to monitor them early on to assess cardiovascular risk accurately.