This article is more than 5 years old. Information may no longer be current.
Apheresis one of few options to reduce Lp(a)
Click Here to Manage Email Alerts
LAS VEGAS — Lipid apheresis can significantly reduce lipoprotein(a) levels compared with available drug therapies, according to a presentation at National Lipid Association Scientific Sessions.
Patrick M. Moriarty, MD, FNLA, professor of medicine and director of clinical pharmacology and The Atherosclerosis/Lipoprotein-Apheresis Center at University of Kansas in Kansas City, reviewed present therapies for CVD prevention and noted that only lipid apheresis has been demonstrated to dramatically reduce Lp(a) with a corresponding reduction in CVD events.
Statins have been shown to raise Lp(a) levels by up to 20% in some instances, and elevate oxidized phospholipids which are bound to Lp(a), Moriarty said. Regardless, he said, statins improve CVD in high-CV risk patients, such as the JUPITER trial, where those treated with rosuvastatin (Crestor, AstraZeneca) had reduced LDL levels below 55 mg/dL, resulting in a 44% reduction in CV events.
In a retrospective analysis of the JUPITER trial, researchers analyzed patients with high and low levels of Lp(a). Although the incidence of CVD was lowered, the treatment effect of rosuvastatin for the MI, stroke, revascularization and mortality was lessened in patients with high Lp(a) levels.
“It wasn’t that you shouldn’t use a statin for patients with elevated Lp(a), but don’t expect as much bang for your buck when you do have a high Lp(a) patient,” Moriarty said.
Diets that are low fat increase Lp(a), regardless of the quantity of vegetables consumed, and physical activity has little effect on these levels, according to the presentation. Niacin therapy reduces oxidized phospholipid and Lp(a) levels, though its ability to lower rates of CVD events has not been demonstrated in clinical trials. Hormone replacement therapy and aspirin have reduced CVD events and Lp(a) levels, Moriarty said.
Mipomersen (Kynamro, Kastle Therapeutics), a newer drug, has been shown to reduce LDL between 25% and 30%. It also reduces Lp(a) levels by a significant amount.
“Unfortunately ... the company that markets and manufactures this drug has decided to drop the drug from the market,” Moriarty said, noting that its fate is uncertain.
A study on patients treated with alirocumab (Praluent, Sanofi/Regeneron), a drug that decreases LDL by upregulating LDL receptors found that there was no consistent correlation between LDL and Lp(a) reduction. More than 40% of patients who received PCSK9 antibodies had significant LDL reductions with minimal to no change to Lp(a) levels. This may be a result of the degradation Lp(a) not being significantly dependent on LDL receptors.
Aggressive reduction of Lp(a) by 65% to 70% can be achieved with lipid apheresis, resulting in significant decrease in CV events, he said.
Since Lp(a) mass consists of 30% to 45% LDL, when a lab measures LDL, 30% to 45% of the Lp(a) mass is part of that measurement. This might explain the reason some patients are resistant to LDL lowering with statins, ezetimibe or PCSK9 inhibitors, since they have little to no effect on Lp(a), Moriarty said.
Guidelines for the use of apheresis are currently available in areas such as Germany, Japan and North America.
Over the past 10 years, three papers have been published on the benefits of lipid apheresis therapy on patients with CVD and elevated Lp(a) levels (> 60mg/dL) in German apheresis centers. The treatment reduced Lp(a) and incidence of major adverse CV events, Moriarty said.
In Germany, the use of lipid apheresis for patients with isolated elevated Lp(a) levels is seen more often than for patients with heterozygous or homozygous familial hypercholesterolemia, according to the presentation.
At the University of Kansas Medical Center, which is the largest lipid apheresis center in North America, patients who had an elevated levels of Lp(a) (> 100mg/dL) irrespective of LDL levels had significantly reduced CVD events after initiating lipid-apheresis and had decreased LDL, corrected LDL and Lp(a) levels and reduced instances of major adverse CV events, Moriarty said.
Increased levels of Lp(a) can increase the risk for stroke, according to the presentation. The risk for acute ischemic stroke increases fourfold in children with elevated Lp(a) levels and the risk for recurrent ischemic stroke also increases by more than 10 times in patients with elevated Lp(a), Moriarty said.
Potential future treatments to Lp(a) levels include RNA-targeted antisense and RNA interference, according to the presentation. An antisense oligonucleotide (AKCEA-APOCIII-LRx, Akcea Therapeutics/Ionis/Novartis) has been shown to reduce Lp(a) by 90%, and the reduction continued 3 months after the last dose. The second-generation agent is more specific to the liver, thus lowering the dose by 10-fold, which results in a reduction of adverse side effects, he said.
An RNA interference drug (ARC-LPA) being developed by Amgen to reduce Lp(a) just started phase 1 human trials this year, according to the presentation.
The timing of Lp(a) measurement can be critical for initiating treatment and preventing CVD and understanding how much of corrected LDL may be treatable with present lipid-modifying therapy, Moriarty said.
“Everyone should have their Lp(a) levels at least once in their lifetime and as early as possible,” he said. “It’s ridiculous we’re not doing that now and we should push health care insurance companies and the government to do this. We only need it once and it should be done as soon as we can.” – by Darlene Dobkowski
Reference:
Moriarty PM. Session VII – Lipoprotein(a) as a Risk Factor and Treatment Target for CVD. Presented at: National Lipid Association Scientific Sessions; April 26-29, 2018; Las Vegas.
Disclosure: Moriarty reports he has relationships with Aegerion, Akcea, Amarin, Amgen, Duke Clinical Research Institute, Eliaz Therapeutics, Espirion, FH Foundation, Ionis, Gemphire Therapeutics, Kaneka, Kastle Therapeutics, Kowa, Lilly, Novartis, Pfizer, Regeneron, RegenXBio, Sanofi, Stage II Innovations, University of Pennsylvania and Zydus Discovery.