Assessing the impact of PCSK9 inhibition on coronary plaque phenotype with optical coherence tomography: rationale and design of the randomized, placebo-controlled HUYGENS study.

Background Technological advances in arterial wall imaging permit the opportunity to visualize coronary atherosclerotic plaque with sufficient resolution to characterize both its burden and compositional phenotype. These modalities have been used extensively in clinical trials to evaluate the impact of lipid lowering therapies on serial changes in disease burden. While the findings have unequivocally established that these interventions have the capacity to either slow disease progression or promote plaque regression, depending on the degree of lipid lowering achieved, their impact on plaque phenotype is less certain. More recently optical coherence tomography (OCT) has been employed with a number of studies demonstrating favorable effects on both fibrous cap thickness (FCT) and the size of lipid pools within plaque in response to statin treatment. Methods The phase 3, multi-center, double-blind HUYGENS study will assess the impact of incremental lipid lowering with the proprotein convertase subtilisin kexin type 9 (PCSK9) inhibitor, evolocumab, on plaque features using serial OCT imaging, in statin-treated patients following an acute coronary syndrome (ACS). Subjects with non-ST-elevation ACS (n=150) will be randomized 1:1 into two groups to receive monthly injections of evolocumab 420 mg or placebo. Results The primary endpoint is the effect of evolocumab on coronary atherosclerotic plaques will be assessed by OCT at baseline and at week 50. Conclusions The HUYGENS study will determine whether intensified lipid lowering therapy with evolocumab in addition to maximally tolerated statin therapy will have incremental benefits on high-risk features of coronary artery plaques. Trial registration This study was registered on Clinicaltrials.gov (NCT03570697).