Category: Triglycerides

Antisense Inhibitors of ApoC3 and Lp(a) Show Positive Results in Phase 1 and 2 Studies

In a Phase 2 trial, patients with very high to severely high triglycerides who were treated with the investigational drug, volanesorsen (Akcea Therapeutics), a second-generation antisense inhibitor of apolipoprotein C-III (ApoC3) synthesis, achieved mean reductions of up to 80% in ApoC3 and up to 71% in triglycerides. HDL-C levels increased, on average, up to 46%. The trial was double-blinded, randomized, placebo-controlled, and conducted over 13 weeks to assess the safety and activity of volanesorsen as monotherapy and as an add-on to fibrates. Phase 3 study (APPROACH) is ongoing in patients with familial chylomicronemia syndrome (FCS) and another Phase 3 study is planned for later this year in patients with familial partial lipodystrophy (FPL). Read more

Is There More to CHD Risk than LDL Cholesterol?

Which of the many so called “risk factors” correlated with Coronary Heart Disease (CHD) actually cause disease? According to Dr. Sekar Kathiresan, genetic discoveries are proving crucial to disentangling cause from correlation. Dr. Kathiresan will present the session Is There Anything More to CHD Risk than LDL Cholesterol?” on Thursday, October 23, 2014 at the 9th Annual CMHC.

“Our work to date,” he said, “suggests that there are three lipid fractions that show evidence in terms of a causal relationship: LDL; lipoprotein(a); and triglyceride-rich lipoproteins (TRLs). In contrast, although low levels of HDL are correlated with CHD risk, low HDL levels do not represent a causal relationship.”

“The good news,” Dr. Kathiresan continued, “is that there is something beyond LDL. Naturally occurring genetic mutations in four different genes alter triglycerides and CHD risk. In a recent study, it was found lifelong lower levels of APOC3 caused by a genetic mutation led to a 50% reduced risk of CHD… We’re in an interesting phase, where there’s a resurgence of interest in TRLs. The challenge over the next few years will be in proving that reducing TRLs will not only lower triglycerides but also the risk of CHD.”

The Role of Inflammation

In their Thursday morning keynote address, Drs. Peter Libby and Paul Ridker will also address CHD risk factors beyond lipids by presenting their research on the role of inflammation in the pathophysiology of atherosclerosis and the impact anti-inflammatory therapies under investigation may have on reducing cardiovascular event rates. “The magnitude of independent risk associated with inflammation is at least as large, if not larger, than that of blood pressure and cholesterol,” said Dr. Paul Ridker.

View CMHC highlights – visit CMHC Rewind for featured presentations from the 2014 CMHC.