Efficacy of PCSK9 inhibitors in patients with peripheral artery disease: insights from the AT-TARGET-IT Registry

Background/Introduction Peripheral arterial disease (PAD) is associated with a high risk of major adverse cardiovascular and limb events. LDL-cholesterol (LDL-C) lowering improves outcomes in PAD, and randomized evidence supports the use of proprotein convertase subtilisin/kexin type-9 inhibitors (PCSK9i) on top of statin ± ezetimibe therapy. Yet, real-world data on PCSK9i use and efficacy in this population remain limited. Purpose AT-TARGET-IT is an Italian, multicenter, observational registry on the use of PCSK9i in clinical practice. The purpose of this subanalysis was to investigate efficacy and safety of PCSK9i in patients with PAD. Methods Patients with PAD initiating evolocumab or alirocumab (75, 150 or 300 mg), according to ESC/EAS Guidelines indications and national reimbursement criteria, were enrolled in the AT-TARGET-IT registry. Clinical characteristics and lipid profile were collected at baseline and at subsequent follow-ups. Efficacy endpoints included LDL-C reduction and achievement of guideline-recommended LDL-C targets. Results A total of 124 patients with PAD were enrolled in the AT-TARGET-IT registry (61.3% male, median age 59 years), of whom 118 had at least one follow-up recorded. Of these patients, 61.3% had hypertension, 17.7% had type 2 diabetes mellitus, and 21.8% had a previous history of lower limb revascularization. Baseline median ankle brachial index (ABI) was 0.8 (IQR 0.7-0.9), and most patients had symptomatic PAD, predominantly Fontaine stage IIa (30.6%) and IIb (48.4%), while stage III accounted for 17.7%, and stages I and IV were rare (1.6% each). Among patients with at least one follow-up, baseline median LDL-C was 127.1 mg/dL (IQR 101.4-156.4) and decreased to 53.3 mg/dL (IQR 41.2-63.5) after a median time of 17.5 months (p<0.001). Median LDL-C percentage reduction was 61.1% (p<0.001), with 57.6% of patients achieving LDL-C target according to CV risk classification. 43 patients (36%) of PAD patients were on statin therapy, with 31 (72%) of them achieving LDL-C target compared with 51% of PAD patients without statin. Adherence was high (≥80%) in 98.3% of patients, whereas PCSK9i were discontinued in only 2.5% of patients with PAD. No adverse events were reported. Conclusion(s) In this real-world cohort of patients with PAD, PCSK9i provided substantial LDL-C reduction and high adherence. Target attainment was observed in the majority of patients when PCSK9i were used on top of statins. These findings are consistent with major clinical trials and support use of PCSK9i tolerability in real-world clinical practice.