Promising New Drug Targets Genetic Cholesterol, Significantly Reduces Risk of Heart Attacks

Recent research has unveiled a groundbreaking experimental medication capable of substantially lowering levels of a specific cholesterol-like particle linked to increased heart attack and stroke risks. Known as lipoprotein(a) or Lp(a), many individuals remain unaware of its presence within their bloodstream.

Unlike typical cholesterol levels that can be modified through lifestyle adjustments, elevated Lp(a) levels pose a different challenge. Cleveland Clinic researchers have categorized this condition as “one of the last untreatable frontiers of cardiovascular risk.”

Understanding the Mechanism of Lepodisiran

The latest findings confirm previous research that highlights the efficacy of lepodisiran, an experimental drug developed by Eli Lilly and backed by the study’s funding. This innovative drug operates by “silencing” the primary gene responsible for the synthesis of Lp(a).

Cleveland Clinic also notes that several other experimental gene therapies with comparable mechanisms are in various stages of development. The significant results from the study were published in The New England Journal of Medicine and showcased at the American College of Cardiology annual meeting held on March 30.

The Prevalence of Lipoprotein(a)

According to the American Heart Association, approximately 20-25 percent of the global population has elevated levels of Lp(a). This equates to around 64 million individuals in the United States alone and approximately 1.4 billion worldwide.

Lp(a) shares a resemblance with low-density lipoprotein (LDL), commonly labeled as “bad cholesterol.” However, research indicates that Lp(a) is more susceptible to causing plaque buildup and blood clots within arteries, leading to higher cardiovascular risks.

Dr. Steven Nissen, chief academic officer at Cleveland Clinic’s Heart, Vascular & Thoracic Institute, emphasizes the severity of Lp(a)’s impact. He refers to it as an independent risk factor for heart disease largely determined by genetic factors, contrasting it with LDL levels influenced by various environmental components.

Genetic Insights into Lipoprotein(a)

Dr. Deepak L. Bhatt, director of the Mount Sinai Fuster Heart Hospital, elaborates on the genetic nature of Lp(a). He explains that while Lp(a) levels are determined by variations in a single gene, LDL cholesterol levels reflect the influence of multiple genes. This distinction highlights the challenges in addressing Lp(a) compared to traditional cholesterol levels.

Experts clarify that while lifestyle choices such as diet, exercise, and weight management can effectively lower LDL levels, they do not impact Lp(a) concentrations. Furthermore, there are currently no approved medications that can reduce Lp(a) levels, creating a gap in treatment options.

The Clinical Trial Process

A recent clinical trial involving 320 participants took place across multiple countries, including the United States, from November 11, 2022, to April 17, 2023. Individuals were randomly assigned to receive either a placebo or one or two subcutaneous injections of lepodisiran. Initial assessments indicated that participants displayed significantly elevated Lp(a) levels, with an average exceeding 250 nanomoles per liter.

After administering a single injection of the highest dose, results showed nearly a 100 percent reduction in Lp(a) levels after six months. Those receiving a second dosage at the six-month mark sustained this remarkable reduction at the one-year follow-up.

Implications for Cardiovascular Health

Cardiologists are optimistic about the implications of these findings for millions of Americans burdened by high Lp(a) levels. Dr. Bhatt termed the outcomes as “very impressive,” underscoring the potential of this treatment in revolutionizing the management of cardiovascular risk.

Despite the promising results, the study reported minor injection site reactions in 12 percent of participants, with no significant safety concerns raised. However, the research has limitations, including the underrepresentation of Black participants, who demonstrate a higher likelihood of elevated Lp(a) levels. Ongoing studies aim to address this diversity in patient demographics, particularly in the larger phase 3 trials.

Future Directions in Research

One critical question remains unanswered: Does lowering Lp(a) significantly reduce the risk of heart attacks and strokes? Expert opinions reveal the necessity of phase 3 trials to ascertain the long-term clinical impacts of the treatment. Dr. Nissen confirmed that such trials are currently underway to explore this critical relationship.

Both the European Society of Cardiology and the National Lipid Association in the United States recommend routine Lp(a) level assessments for all adults. Dr. Bhatt highlights his long-standing practice of monitoring Lp(a) levels in all patients, given its genetic determination.

Lp(a) Testing: A Simple Yet Critical Step

In contrast to traditional cholesterol, which requires periodic monitoring, Nissen emphasizes that Lp(a) testing is a one-time necessity for most individuals due to its genetic consistency over a lifetime. He reveals that levels remain stable from early adulthood into later years, suggesting that early identification can empower individuals to manage their health proactively.

Overall, this emerging research offers a beacon of hope for addressing a previously untreatable aspect of cardiovascular risk, potentially transforming preventive strategies for millions impacted by genetic cholesterol abnormalities.