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Effect of Evolocumab and Statin on Coronary Plaque After MI
Quick Takes
- Evolocumab, in combination with statin therapy, produces atheroma stabilization and regression following an NSTEMI demonstrating a potential mechanism for improved clinical outcomes for patients with very low LDL-C levels.
- The most effective lipid-lowering regimens should be implemented following an acute coronary syndrome to lower risk of future cardiovascular events.
Study Questions:
Does evolocumab favorably modify coronary plaque phenotype in patients with recent non–ST-segment elevation myocardial infarction (NSTEMI)?
Methods:
Patients were randomized to receive evolocumab 420 mg or placebo monthly for 52 weeks following an NSTEMI. Serial optical coherence tomography (OCT) and intravascular ultrasound imaging in a matched segment of a nonculprit vessel were measured at baseline and at week 50. Clinical events were self-reported. The primary endpoint was the nominal change in minimum fibrous cap thickness (FCT) at any point throughout the matched arterial segment from baseline to week 50. The maximum lipid arc was a secondary endpoint. Other exploratory analyses included OCT features in lipid-rich plaque regions and plaque burden. Safety and tolerability were also evaluated. A sample size of 125 patients was required to provide a statistical power of 90%.
Results:
A total of 135 patients had evaluable OCT imaging at baseline and follow-up (n = 65 evolocumab, n = 70 placebo). Study drug was administered for a mean of 11.2 months. The majority of patients were also treated with statin therapy (80.7% high-intensity, 13.7% moderate-intensity). Nonculprit arteries imaged included left anterior descending: 37.6%, circumflex: 28.1%, right coronary: 33.7%, ramus: 0.6%.
Evolocumab-treated patients had a greater increase in the minimum FCT (+42.7 µm vs. +21.5 µm; p = 0.015) and a greater decrease in maximum lipid arc (-57.5° vs. -31.4°; p = 0.04) at any point in the artery segment compared to placebo. There was also a greater regression of atheroma volume in patients treated with evolocumab compared to placebo (-2.29% ± 0.47% vs. -0.61% ± 0.46%; p = 0.009). Rates of adverse cardiovascular events were low and not significantly different between groups. Evolocumab was well tolerated with no significant increases in injection site reactions or myalgias.
Conclusions:
Addition of evolocumab to statin therapy following an NSTEMI produced incremental benefits on plaque phenotype consistent with stabilization and regression. These changes offer a potential mechanism for improved clinical outcomes observed by achieving very low low-density lipoprotein cholesterol (LDL-C) levels with proprotein convertase subtilisin kexin type-9 (PCSK9) inhibitors.
Perspective:
This study supports the systemic nature of atherosclerotic disease in acute coronary syndrome (ACS) with >90% of patients having lipid-rich plaques in nonculprit arteries. Patients treated with statin therapy alone had significant improvements in plaque phenotype; however, the addition of evolocumab was associated with even greater improvement in these plaque features. The results of this study suggest that achieving very low LDL-C following ACS may favorably modify the composition of underlying atherosclerotic disease. The impact of these findings on early cardiovascular risk remains to be determined.
Clinical Topics: Acute Coronary Syndromes, Cardiovascular Care Team, Diabetes and Cardiometabolic Disease, Dyslipidemia, Noninvasive Imaging, Prevention, Stable Ischemic Heart Disease, Vascular Medicine, Lipid Metabolism, Nonstatins, Novel Agents, Statins, Echocardiography/Ultrasound, Chronic Angina
Keywords: Acute Coronary Syndrome, Atherosclerosis, Cholesterol, LDL, Diagnostic Imaging, Dyslipidemias, Hydroxymethylglutaryl-CoA Reductase Inhibitors, Myalgia, Non-ST Elevated Myocardial Infarction, Patient Care Team, PCSK9 protein, human, Phenotype, Plaque, Atherosclerotic, Proprotein Convertase 9, Primary Prevention, Risk Factors, Tomography, Optical Coherence, Ultrasonography
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