Lp(a) confers increased CVD risk, but treatment options unclear

NEW ORLEANS — While multiple studies have shown that lipoprotein(a) is associated with elevated risk for CVD, treatments to reduce lipoprotein(a) have not yet proven to reduce CVD risk, an expert said at the National Lipid Association Scientific Sessions.

The addition of agents that lower lipoprotein(a), or Lp(a), such as niacin and cholesteryl ester transfer protein inhibitors, to statin therapy have not improved outcomes, leaving clinicians unclear how best to treat their patients with high Lp(a) levels, Christie M. Ballantyne, MD, professor of medicine and molecular and human genetics at Baylor College of Medicine, Houston; director of the Maria and Alando J. Ballantyne, MD, Atherosclerosis Clinical Research Laboratory at Baylor College of Medicine; co-director of the Lipid Metabolism and Atherosclerosis Clinic at The Methodist Hospital, Houston; and director of the Center for Cardiovascular Disease Prevention at Methodist DeBakey Heart Center, said during a presentation.

Christie M. Ballantyne

According to Ballantyne, research is being conducted with PCSK9 inhibitors and a novel antisense agent to refine the role of Lp(a) in CVD risk.

Research indicates that high levels of Lp(a) are associated with increased CVD risk even after statin therapy, he said, noting that statins increase Lp(a) levels, as does ezetimibe (Zetia, Merck).

Results of the JUPITER trial showed that while rosuvastatin (Crestor, AstraZeneca) reduced incident CVD in white participants regardless of Lp(a) level, residual CVD risk in the study population was higher in those with Lp(a) levels above the median, Ballantyne said.

The AIM-HIGH trial demonstrated that adding niacin to statin therapy reduced Lp(a) by 21%, but had no effect on CV events, he said. However, a subsequent analysis of that population showed that high Lp(a) level was a predictor of CVD events in patients with LDL as low as 54 mg/dL.

In the FATS study, Lp(a) was not associated with progression of atherosclerosis after statin therapy, but an IVUS analysis of participants from the SATURN trial, to be presented at the 2016 European Society of Cardiology Congress, may offer new insights, he said.

A novel antisense drug (IONIS-APO(a)-L_RX, Ionis Pharmaceuticals) is designed to lower Lp(a) by attacking apolipoprotein(a) at a specific messenger RNA site. The drug has successfully lowered Lp(a) by more than 80% in phase 1 studies, according to Ballantyne.

“Using a very small dose appears to be quite favorable in reducing adverse reactions and enhancing tolerability,” he said. “This is a very important advancement” and could provide the best test of the hypothesis that lowering Lp(a) reduces CV events.

According to Ballantyne, “ongoing outcome trials of PCSK9 inhibitors will examine whether high-risk patients, some of them with high Lp(a), will get a benefit from this therapy. I don’t know if it will be possible to tease out whether this is due to lowering of Lp(a) or lowering of other ... lipoproteins.” – by Erik Swain

Reference:

Ballantyne CM. Drugs in Development to Treat Lp(a): Risk Reduction vs. Lowering a Number – What Can We Expect? Presented at: National Lipid Association Scientific Sessions; May 19-22, 2016; New Orleans.
Disclosure: Ballantyne reports receiving institutional grant/research support from Abbott Diagnostics, Amarin, Amgen, Eli Lilly, Esperion, Novartis, Otsuka, Pfizer, Regeneron, Roche Diagnostics, Sanofi-Synthelabo and Takeda; and consulting for Abbott Diagnostics, Amarin, Amgen, AstraZeneca, Eli Lilly, Esperion, Genzyme, Ionis, Matinas BioPharma, Merck, Novartis, Pfizer, Regeneron, Roche Diagnostics and Sanofi-Synthelabo.