Reply: Identifying vulnerable coronary atherosclerotic plaques: from theory to practice

We sincerely appreciate Dr Dimitriadis and colleagues’ interest in our study1, which aimed to evaluate the prognostic value of vulnerable plaque features in predicting the incidence of the lesion-oriented composite endpoint in fractional flow reserve (FFR)-negative non-culprit lesions in patients with diabetes mellitus2. The authors have rightly highlighted the demonstrated benefit of proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors in plaque regression and stabilisation, which recent studies have associated with reduced adverse outcomes3. Although we share the authors’ enthusiasm for these potent cholesterol-lowering therapies, it is important to note that the first PCSK9 inhibitors (alirocumab and evolocumab) received European Commission approval for reducing cardiovascular risk in patients with established atherosclerotic cardiovascular disease in 2018 and 2019, respectively. However, our study analysed patients enrolled between 2015 and 2018, a period preceding the widespread use of these therapies. Currently, the COMBINE-INTERVINE randomised trial (ClinicalTrials.gov: NCT05333068) is enrolling patients and will likely include a substantial proportion of patients receiving novel low-density lipoprotein (LDL)-lowering pharmacotherapies, such as PCSK9 inhibitors and therapies based on small interfering ribonucleic acid technology. We are convinced...