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Evolocumab and Coronary Disease Progression

JAMA; ePub 2016 Nov 15; Nicholls, et al

Publish date:

The addition of evolocumab among patients with angiographic coronary disease treated with statins resulted in a greater decrease in percent atheroma volume (PAV) after 76 weeks of treatment, when compared to placebo. This according the GLAGOV double-blind, placebo-controlled, randomized clinical trial from May 3, 2013, to January 12, 2015, that included participants with angiographic coronary disease who were randomized to receive monthly evolocumab (420 mg; n=484) or placebo (n=484) via subcutaneous injection for 76 weeks, in addition to statins. Researchers found:

  • Among the 968 treated patients (mean age, 59.8 years; mean LDL-C level, 92.5 mg/dL), 846 had evaluable imaging at follow-up.
  • The evolocumab group achieved lower mean, time-weighted LDL-C levels, compared with placebo.
  • PAV increased 0.05% with placebo and decreased 0.95% with evolocumab.
  • Normalized total atheroma volume (TAV) decreased 0.9 mm3 with placebo and 5.8 mm3 with evolocumab.
  • Evolocumab also induced plaque regression in a greater percentage of patients than placebo.

Citation:

Nicholls SJ, Puri R, Anderson T, et al. Effect of evolocumab on progression of coronary disease in statin-treated patients. [Published online ahead of print November 15, 2016]. JAMA. doi:10.1001/jama.2016.16951.

Commentary:

Statins are very effective medications at decreasing LDL-cholesterol and decreasing cardiac events both for people with established coronary artery disease (CAD) and in primary prevention of CV disease. Nonetheless, many people with established CAD do not achieve LDL levels below 100 mg/dl, and even more people do not achieve very low LDL-cholesterol levels, below 70 mg/dl. Achieving very low LDL-cholesterol has been shown to be associated with regression of plaque.1,2 In addition, despite statin use, residual risk remains with progression of atherosclerotic plaque leading to unstable angina, MI and stroke. It is in this context that the PCSK-9 inhibitors are being evaluated as medications that may have benefit in addition to statins. This trial shows that evolocumab in addition to a statin leads to regression of plaque as measured by IVUS compared to use of a statin alone. While percent atheroma volume (PAV) has been shown to be related to CV endpoints3,4, it remains a surrogate marker for what we really care about, which is unstable angina, MI and stroke. Studies showing the effect of the PCSK-9 inhibitors on these hard endpoints are ongoing and expected to be reported in the next 1 to 2 years. —Neil Skolnik, MD

  1. Nissen SE, Tuzcu EM, Schoenhagen P, et al. Effect of intensive compared with moderate lipid-lowering therapy on progression of coronary atherosclerosis: a randomized controlled trial. JAMA. 2004;291:1071–80.
  2. Nissen SE, Nicholls SJ, Sipahi I, et al. Effect of very high-intensity statin therapy on regression of coronary atherosclerosis: the ASTEROID trial. JAMA. 2006;295:1556–65.
  3. Nicholls SJ, Hsu A, Wolski K, et al. Intravascular ultrasound-derived measures of coronary atherosclerotic plaque burden and clinical outcome. J Am Coll Cardiol. 2010;55(21):2399-2407.
  4. Puri R, Nissen SE, Shao M ,et al. Coronary atheroma volume and cardiovascular events during maximally intensive statin therapy. Eur Heart J. 2013;34(41):3182-3190.

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