To the Editor In a prespecified analysis from the Further Cardiovascular Outcomes Research With PCSK9 Inhibition in Subjects With Elevated Risk (FOURIER) trial, Wiviott et al1 demonstrated that low-density lipoprotein cholesterol–lowering therapy with evolocumab resulted in a significant reduction across different types of myocardial infarction (MI), including procedural MI. Notably, the reduction in procedural MI did not emerge immediately, and the separation of Kaplan-Meier curves was apparent after 6 months of commencing evolocumab.1 It is plausible that these clinical benefits in procedural MIs were related to plaque stabilization; nonetheless, evidence to delineate how atherosclerotic plaque became less vulnerable is mechanistically needed. Reduction in atherosclerotic plaque lipid burden has a stabilizing effect; however, it occurred as early as 7 weeks in response to lipid-lowering therapy.2 Such time course does not match the relatively late onset of benefits in patients receiving evolocumab in the FOURIER trial.1 Moreover, data from the Chemometric Observation of Lipid Core Plaques of Interest in Native Coronary Arteries (COLOR) registry showed a lack of association between procedural adverse outcomes and atherosclerotic lipid burden when quantified using near-infrared spectroscopy.3 On the other hand, fibrous cap thickness quantified using optical coherence tomography was the most important predictor of procedural MI.4 Moreover, cap thickness remained an independent predictor of procedural MI even after adjusting for lipid volume on near-infrared spectroscopy and plaque burden using intravascular ultrasonography.4 Whether the reduction in procedural MI in response to PCSK9 inhibitors was related to increased thickness of fibrous cap would be better understood following the results of the Efficacy of Alirocumab for Thin-Cap Fibroatheroma in Patients With Coronary Artery Disease Estimated by Optical Coherence Tomography (ALTAIR) trial.5
Alkhalil M. Myocardial Infarction and Evolocumab. JAMA Cardiol. 2021;6(10):1221–1222. doi:10.1001/jamacardio.2021.1997
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