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Vascepa Lowers Lipoprotein-Associated Phospholipase A2 (Lp-PLA2)

|Includes: Amarin Corporation PLC (AMRN)

Vascepa, when combined with statin, reduced lp-PLA2 by 19% over statin alone at a 4g/day dose for a duration of 12 weeks in the ANCHOR population (200-499mg/dL trigs).

Familiarize yourself with lp-PLA2 by watching this video:

Listen to these insightful comments from the 2007 American Heart Association Scientific Sessions entitled "Advances in the Detection of Rupture-Prone Plaque: The Role of Lp-PLA2 in Cardiovascular Risk Assessment.":

Keep in mind the information on risk of stroke.

Let's look at a testing center's summary of lp-PLA2:

Clinical Background

Traditional markers of lipidemia identify only about half of the individuals at risk of cardiovascular disease (NYSE:CVD).1 Atherosclerosis is now recognized as an inflammatory disease, and inflammatory markers, most notably high-sensitivity C-reactive protein (hs-CRP), have been shown to identify additional individuals who are at risk. Lipoprotein-associated phospholipase A2 (Lp-PLA2) is another marker of vascular inflammation, and because it is not associated with systemic inflammation it is more vascular-specific than is CRP.2 It is produced by macrophages and other inflammatory cells and is found in atherosclerotic lesions.

Increased blood levels of Lp-PLA2 have been linked to increased risk for: 1) cerebral thrombosis,3 2)
first4 and recurrent5 coronary events, 3) adverse prognosis after acute coronary syndrome,6 and 4) CVD associated with metabolic syndrome7 or type 2 diabetes mellitus.8 Evidence from more than 25 prospective studies has shown an approximate doubling of risk for coronary artery disease (NYSEARCA:CAD), CVD, and stroke when comparing Lp-PLA2 values in the top quintile versus the bottom quintile.2 The predictive value typically remains after adjustment for LDL-cholesterol and other established CVD risk factors.2

Now let's look at an article from the American Journal of Cardiology, Volume 101, Issue 12 Supplement, 16 June 2008, Pages S41-S50

From Figure 2:

Figure 2. Elevated lipoprotein-associated phospholipase A2 (Lp-PLA2) is consistently associated with a doubling of risk for cardiovascular disease (CVD). Published prospective epidemiologic studies show the association of elevated Lp-PLA2 (top quantile vs bottom quantile) with cardiovascular risk. A fairly consistent near doubling of risk is associated with elevated Lp-PLA2. Results are fully adjusted for traditional risk factors, lipids, and often for body mass index and high-sensitivity C-reactive protein

So we have a treatment with adverse effects similar to placebo that will lower an important, specific cardiovascular risk marker. This is one factor into why Vascepa looks to be a promising option for those at risk for any major, adverse cardiovascular event.

Now back to stroke risk, in the JELIS study, where patients were given 1.8 grams EPA a day with statin vs. statin and placebo, those patients with a prior history of stroke, saw a 20% relative reduction in recurrent stroke in the EPA/statin group vs. the statin and placebo group.

In the secondary prevention subgroup, stroke occurred in 48 (10.5%) of 457 no EPA group and in 33 (6.8%) of 485 EPA group, showing a 20% relative reduction in recurrent stroke in the EPA group (Hazard Ratio, 0.80; 95% confidence interval, 0.64 to 0.997).


Administration of highly purified EPA appeared to reduce the risk of recurrent stroke in a Japanese population of hypercholesterolemic patients receiving low-dose statin therapy.

lp-PLA2 is associated with unstable or ruptured plaques, just how does EPA (Vascepa) involve itself in improving the actual structural morphology of these plaques? Next time.

Disclosure: I am long AMRN.