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Elevated Lipoprotein(a) Levels Linked to Heart Disease; New Drug Shows Promise
An estimated one in five individuals in the United States, approximately 64 million people, are believed to have elevated levels of lipoprotein(a), or Lp(a), a tiny particle in the bloodstream. This condition can significantly heighten the risk of serious cardiovascular events, including heart attacks and strokes. Despite the prevalence and potential danger, awareness remains low, with routine testing uncommon due to the historical lack of effective treatments. Neither dietary adjustments nor increased physical activity have proven effective in lowering Lp(a) levels, and until recently, no pharmaceutical interventions were available. However, this landscape may be poised for change with the development of novel therapies.
Breakthrough Drug Shows Significant Lp(a) Reduction
Cardiologists recently announced promising findings regarding lepodisiran, an investigational medication developed by Eli Lilly. Clinical trial data indicates that a single dose of this experimental drug resulted in a remarkable 94 percent reduction in Lp(a) levels. The therapeutic effects were sustained for six months, and the initial studies reported no major adverse reactions. This research, presented at the American College of Cardiology annual meeting and published in the New England Journal of Medicine, signifies a potential turning point in addressing elevated Lp(a).
Ongoing Research to Confirm Cardiovascular Benefit
While lepodisiran demonstrates significant Lp(a) lowering capabilities, crucial large-scale clinical trials are currently underway to determine if reducing Lp(a) levels directly translates to a decreased incidence of heart attacks, strokes, and cardiovascular death. Several pharmaceutical companies, beyond Eli Lilly, are actively engaged in developing innovative drugs designed to impede the body’s production of Lp(a), a complex particle comprised of lipids and a protein. The outcomes of these ongoing trials are eagerly anticipated by the medical community.
Expert Opinions on Lp(a) Treatments
Dr. David Maron, a preventive cardiologist at Stanford University, who was not involved in the Eli Lilly study, described the substantial and sustained reduction in lipoprotein levels achieved with lepodisiran as “thrilling.” Dr. Martha Gulati, a preventive cardiologist at Cedars-Sinai Medical Center, also independent of the trial, lauded the research as “really elegant,” highlighting the rigor and potential impact of the findings.
Timeline for Trial Results and Future Availability
Eli Lilly’s pivotal clinical trial, designed to assess the drug’s ability to prevent heart attacks, strokes, and cardiovascular-related fatalities, is projected to conclude in 2029. However, results from trials evaluating other Lp(a)-targeting drugs are expected sooner. Notably, a study of a Novartis drug, administered via monthly injections, is anticipated to yield results as early as 2026. These upcoming data readouts will be critical in defining the future of Lp(a) management and its impact on cardiovascular health.
Cautionary Notes and Lessons from Past Research
Despite the optimism surrounding these new therapies, cardiologists advise caution. Past experiences serve as a reminder that altering a risk factor does not automatically guarantee a reduction in overall risk. The history of HDL-raising drugs, initially believed to be beneficial based on observational data, underscores this point. While raising HDL (“good cholesterol”) seemed promising, these drugs ultimately failed to demonstrate clinical benefit, highlighting the complexities of cardiovascular disease and the need for definitive evidence from clinical trials.
Lp(a) as a Key Frontier in Cardiology
Dr. Daniel Rader, a preventive cardiologist at the University of Pennsylvania’s Perelman School of Medicine, characterized Lp(a)-lowering therapies as “a huge new frontier in cardiovascular medicine.” He emphasized the significance of these developments in addressing a genetically determined risk factor for heart disease that has long been untreatable.
Understanding Lp(a) and its Genetic Basis
Lipoprotein(a) was identified as a genetically determined risk factor for cardiovascular disease in 1974. Unlike other risk factors influenced by lifestyle, Lp(a) levels are primarily controlled by an individual’s genes. Individuals with moderately elevated Lp(a) face an approximate 25 percent increase in heart attack or stroke risk. Alarmingly, about 10 percent of the population has very high Lp(a) levels, which can double this risk.
Clinical Significance of Lp(a) Levels
Cardiologists frequently observe elevated Lp(a) in patients experiencing heart attacks or strokes without traditional risk factors such as high cholesterol, high blood pressure, or smoking. Often, these individuals also have a family history of premature heart disease, suggesting a genetic predisposition linked to Lp(a).
Lp(a) Testing and Patient Identification
According to Dr. Steven Nissen, a preventive cardiologist at the Cleveland Clinic and academic lead for multiple drug trials, Lp(a) testing is particularly crucial for younger individuals presenting with heart attacks. He notes that in patients under 40 experiencing acute myocardial infarction, Lp(a) levels are often significantly elevated, sometimes exceeding 250 nanomoles per liter, far above the normal upper limit of 75.
Personal Stories and the Impact of Lp(a)
Dr. Maron recounts numerous patients in his practice who remained without a clear explanation for their heart disease until Lp(a) testing revealed the underlying cause. Monte Wooden, a 71-year-old retired firefighter, exemplifies this. Despite managing traditional risk factors, Mr. Wooden experienced a heart attack while on statin therapy. A strong family history of early-onset heart disease prompted Lp(a) testing, revealing levels exceeding 400.
Importance of Routine Lp(a) Testing
Preventive cardiologists like Drs. Maron, Gulati, Nissen, and Rader advocate for routine Lp(a) testing for all patients. Given its genetic determination and lifelong stability, Lp(a) levels need only be measured once per individual. Dr. Nissen emphasizes the serious implications of high Lp(a), advising aggressive management of all modifiable risk factors in affected patients.
Underutilization of Lp(a) Testing
Despite expert recommendations, studies indicate that Lp(a) testing remains significantly underutilized. Dr. Gulati highlights data showing that only a fraction of the US population, and even fewer heart disease patients, have undergone Lp(a) testing, despite insurance coverage. She and her colleagues strongly recommend universal Lp(a) screening in adults, advocating for intensified risk factor management in those with elevated levels.
Aggressive Risk Factor Management for High Lp(a)
For patients like Mr. Wooden with high Lp(a), aggressive risk factor intervention is critical. In his case, this involved the use of potent cholesterol-lowering medications, such as Repatha, to achieve very low LDL cholesterol levels.
Patient Experience with Lp(a) Lowering Drugs
Mr. Wooden’s experience further illustrates the potential of Lp(a)-lowering therapies. Participating in a clinical trial for one of these novel drugs, he experienced symptom relief, which recurred upon trial completion, ultimately leading to a quadruple bypass surgery. Dr. Maron acknowledges the anecdotal nature of this observation but suggests it supports the hypothesis that these medications hold promise in preventing heart attacks.