New drug therapies targeting Lp(a) could be a breakthrough in cardiovascular care
There has been an increasing amount of research on lipoprotein (a), or Lp(a), in recent years. Many specialists believe it may be the key to helping address residual cardiovascular risks in patients who are already on optimal preventive medical therapy.
At the recent American Heart Association (AHA) 2024 meeting, Cardiovascular Business interviewed Deepak L. Bhatt, MD, MPH, MBA, director of Mount Sinai Fuster Heart Hospital and the Dr. Valentin Fuster Professor of Cardiovascular Medicine at the Icahn School of Medicine at Mount Sinai, to shed light on this growing area of interest.
He explained that 20-25% of the global population has elevated Lp(a) levels, and recent studies suggest it is an independent and potent marker of residual cardiovascular risk, prompting increased testing and drug development efforts.
"I think in the U.S. we've been a little bit lackadaisical about testing for 'Lp little a' ... some folks do it in lipid clinics and preventive cardiology clinics. I have been testing for a long time, but in particular in folks presenting with premature atherosclerosis, like someone with a myocardial infarction at a young age. But it's probably something we should test in everybody. It's an independent predictive risk beyond say LDL cholesterol or other conventionally measured risk factors," Bhatt explained.
Understanding lipoprotein (a) and its risks
Lp(a) is a genetically determined biomarker associated with an increased risk of atherosclerosis, heart attacks and strokes. Unlike LDL cholesterol, it is not widely tested in routine lipid panels. However, European Society of Cardiology guidelines recommend at least one lifetime Lp(a) test, a practice gaining traction in the U.S. He said the National Lipid Association recently came out with an endorsement that Lp(a) should be measured routinely.
However, like many areas of medicine, testing is not typically performed unless there is something actionable that can be done about it.
"Right now what we can do first of all is identify the patient as being at high risk. So we know, okay, we need to do something more. We can intensify their LDL-lowering regimen, and we know from the PCSK9 inhibitor trials trials like ODYSSEY Outcomes and FOURIER that you get a bit more bang for your buck, with PCSK9 inhibition in patients that in addition to LDL being high, also have elevation of Lp(a)," Bhatt said.
While no FDA-approved treatments specifically target Lp(a), researchers are investigating several new drugs aimed at lowering Lp(a) in ongoing phase three trials that may have results in a couple years. He said other agents are in earlier stage research in the pipeline.
"Of course, when the first trial report is out, if it's say unexpectedly negative, I don't know then what the downstream effects would be to all those drugs that are in the pipeline. But assuming that, as many are expecting, that the initial trial is positive, then I think it'll be just like with LDL lowering, there's lots of different approaches, lots of different drugs and different molecular targets," Bhatt said.
Rising awareness and increased testing for Lp(a)
Interest in Lp(a) testing is growing, as evidenced by the overwhelming demand at the AHA 2024 meeting, where physicians lined up by the hundreds for personal screenings. Bhatt noted that increasing physician awareness is a crucial first step in ensuring at-risk patients receive appropriate testing and, eventually, targeted therapies.
Although questions remain about the full impact of Lp(a)-lowering treatments, the next few years could bring groundbreaking advancements in cardiovascular prevention. For now, Bhatt recommends testing patients for Lp(a) to look for this additional risk factor and watching for updates in this area.
Dave Fornell has covered healthcare for more than 17 years, with a focus in cardiology and radiology. Fornell is a 5-time winner of a Jesse H. Neal Award, the most prestigious editorial honors in the field of specialized journalism. The wins included best technical content, best use of social media and best COVID-19 coverage. Fornell was also a three-time Neal finalist for best range of work by a single author. He produces more than 100 editorial videos each year, most of them interviews with key opinion leaders in medicine. He also writes technical articles, covers key trends, conducts video hospital site visits, and is very involved with social media. E-mail: dfornell@innovatehealthcare.com