Researchers have discovered an experimental medication that considerably reduces a cholesterol type particle that can increase the risk of heart attacks and strokes.
Many Americans are unaware that high levels of this particle – known as lipoprotein (A) or LP (a) – circulate in their blood.
The high LP (a) cannot be changed with lifestyle changes and has been called “one of the last unretifiable borders of cardiovascular risk” by the Cleveland Clinic, which led the study.
This new research has confirmed previous results showing that the experimental medication – Lepodisiran, carried out by Eli Lilly, who financed the study – can “silence” the main gene responsible for the synthesis of the LP (A).
(Other experimental gene therapies with a similar action mechanism are also in development, according to the Cleveland Clinic.)
The results were published in the New England Journal of Medicine and were also presented in the annual meeting of the American College of Cardiology on March 30.
What to know about LP (A)
Lipoprotein levels (A) are raised in around 20 to 25% of people worldwide, according to the American Heart Association.
This is equivalent to around 64 million people in the United States and 1.4 billion people worldwide.
LP (A) Share similarities with another lipoprotein that doctors aim to reduce the risk of heart disease, known as low density lipoprotein (LDL) – often called “bad cholesterol”.
But lipoprotein (A) is more prone to the accumulation of plaque and clots in the arteries than LDL, according to the main author Steven Nissen, MD, university director of the heart, vascular and thoracic institute of the Cleveland Clinic.
“Lipoprotein (A) is an independent risk factor for heart disease which is largely determined by genetics-that is to say that it is inherited,” added Dr. Deepak L. Bhatt, director of Mount Sinai Fuster Heart Hospital and professor of cardiovascular medicine at Icahn School of Medicine of Mount Sinai in New York, Digital. (He was not part of the study.)
LP (A) is mainly determined by differences in a gene, while LDL cholesterol levels are influenced by several genes.
“It is a very big difference, and LDL has a much larger environmental component,” noted Nissen.
“LP (A) is an independent risk factor for heart disease which is largely determined by genetics.”
Diet, exercise and weight loss Can help reduce LDL levels, but they have no impact on LP levels (A), according to experts.
And unlike LDL, which can be reduced with drugs such as statins, there is currently no approved drug treatment which lowers LP (A).
“There is no approved pharmacotherapy for lipoproteins (A) by regulatory authorities in a country of the world,” confirmed Nissen.
Study design
The researchers carried out a clinical trial of 320 people from Argentina, China, Denmark, Germany, Japan, Mexico, the Netherlands, Romania, Spain and the United States from November 11, 2022 to April 17, 2023.
Participants were randomly assigned to receive a placebo or one or two subcutaneous injections from Lepodisiran.
The normal level of LP (A) is less than 75 nanomols per liter and the average level of trial people was around 250 nanomols per liter, Nissen told Fox News Digital.
“They were very high-more than three times the upper limit of normal,” he added.
After injection of the highest dose, participants showed a reduction of almost 100% of lipoprotein levels (A) to six months.
Those who received a second dose at six months maintained a reduction of almost 100% to the one year brand.
In other words, therapy has eliminated almost all lipoproteins (a) of blood, according to Nissen.
Cardiologists say that these results can finally help treat millions of Americans who have high LP (A) levels.
“The results are very impressive,” said Bhatt.
Potential limitations
The researchers noted that there were no major security problems, but 12% of participants reported light reactions on the injection site.
The study had only a few black participants – a population that needs more research, as they are more likely to have high concentrations of lipoprotein (A) than whites, according to previous studies.
(To respond to this concern, researchers register many more black patients in their largest clinical trial of phase 3.)
Another limitation was that only two doses of Lépodisiran were administered in the trial, so that the effect of additional doses is not known.
The study has also not shown that reducing LP levels (A) also reduces the risk of heart attacks and strokes, external experts noted.
“A phase 3 trial testing the clinical impact of this medication is necessary to see if the great reduction in LP (A) results in lower heart attack rates,” said Bhatt.
Nissen confirmed that the phase 3 test to answer this question was already underway.
“Whatever your level when you are 24 years old is the level where you are 64 – it doesn’t change, because it’s genetic.”
The European Cardiology Society and the National Lipid Association in the United States both recommend that all adults check their LP (A) levels.
“I have been checking LP (A) levels in all patients for many years,” said Bhatt.
But unlike traditional cholesterol, which doctors generally monitor over time, Nissen stressed that lipoprotein (a) needs to be checked only once in his life.
“Whatever your level when you are 24 years old is the level you are 64-that doesn’t change, because it’s genetic,” he said.
“So you only need to get it once, and if you get it early in life, you know you are at risk and you can live your life accordingly.”