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Observational Study
. 2021 Jul 1;28(7):754-765.
doi: 10.5551/jat.57653. Epub 2020 Sep 25.

Effects of PCSK9 Inhibitor on Favorable Limb Outcomes in Patients with Chronic Limb-Threatening Ischemia

Yusuke Sato  1 , Hiroyasu Uzui  1 , Tetsuji Morishita  1 , Yoshitomo Fukuoka  1 , Kanae Hasegawa  1 , Hiroyuki Ikeda  1 , Naoto Tama  1 , Kentaro Ishida  1 , Shinsuke Miyazaki  1 , Hiroshi Tada  1
Affiliations
Observational Study

Effects of PCSK9 Inhibitor on Favorable Limb Outcomes in Patients with Chronic Limb-Threatening Ischemia

Yusuke Sato et al. J Atheroscler Thromb. .

Abstract

Aim: The aim of this study was to examine the effects of evolocumab on favorable limb events in patients with chronic limb-threatening ischemia (CLTI).

Methods: A single-center, prospective observational study was performed on 30 patients with CLTI. The subjects were divided into 2 groups based on evolocumab administration: evolocumab-treated (E) group ( n=14) and evolocumab non-treated (non-E) group (n=16). The primary outcome was 12-month freedom from major amputation. The secondary outcomes were 12-month amputation-free survival (AFS), overall survival (OS), and wound-free limb salvage. The mean follow-up period was 18±11 months.

Results: No significant difference was detected between the two groups for the 12-month freedom from major amputation (log-rank p=0.15), while the 12-month AFS rate was significantly higher in the E group than that in the non-E group (log-rank p=0.02). The 12-month OS rate in the E group was shown a tendency for improvement, as compared with that in the non-E group (log-rank p=0.056). Evolocumab administration was not associated with a significant change in freedom from major amputation (HR, 0.23, 95% CI, 0.03-2.07, p=0.19). However, evolocumab administration was related to a tendency for improvement of AFS and OS (HR, 0.13, 95% CI, 0.02-1.06, p=0.056; HR, 0.16, 95% CI, 0.02-1.37, p=0.09, respectively). Moreover, The E group had a higher proportion of wound-free limb salvage at 12 months (92% vs. 42%, p=0.03).

Conclusion: Evolocumab administration was associated with a better AFS outcome in patients with CLTI. Long-term administration of evolocumab over 12 months contributed to improving proportion of wound-free limb salvage.

Keywords: Amputation; Chronic limb-threatening ischemia; Evolocumab; Peripheral artery disease; Proprotein convertase subtilisin/kexin type 9 inhibitor.

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Figures

Fig.1. Study flowchart
Fig.1. Study flowchart
CHD, coronary heart disease; CLTI, chronic limb-threatening ischemia; CVD, cerebrovascular disease; DM, diabetes mellitus; E group, evolocumab-treated group; LDL-C, low-density lipoprotein cholesterol; non-E group, evolocumab non-treated group
Fig.2. Differences in lipid profiles
Fig.2. Differences in lipid profiles
Over time, the patients in the E group were attenuated in levels of LDL-C (A) and non-HDL-C (B) compared to those in the non-E group. The attenuation in MDA-LDL levels (C) persisted through 6 months. E group, evolocumab-treated group; LDL-C, low-density lipoprotein cholesterol; HDL-C, high-density lipoprotein cholesterol; non-E group, evolocumab non-treated group; MDA-LDL, malondialdehyde-modified LDL
Fig.3. Kaplan–Meier curves of 12-month freedom from major amputation, amputation-free survival, and overall survival for the patients with and without evolocumab
Fig.3. Kaplan–Meier curves of 12-month freedom from major amputation, amputation-free survival, and overall survival for the patients with and without evolocumab
A, No significant difference was observed in the 12-month freedom from major amputation between patients with and without evolocumab (log-rank p =0.15). Evolocumab administration was not associated with a significant change in freedom from major amputation (HR, 0.23; 95% CI, 0.03-2.07; p =0.19). B, The 12-month AFS rate was significantly higher in the E group than that in the non-E group (log-rank p =0.02). Evolocumab administration was not related to a significant change in AFS, however there was a tendency to improve AFS (HR, 0.13; 95% CI, 0.02-1.06; p =0.056). C, The 12-month OS rate in the E group was shown a tendency for improvement, as compared with that in the non-E group (log-rank p =0.056). There was a tendency to improve OS (HR, 0.16; 95% CI, 0.02-1.37; p =0.09). AFS, amputation-free survival; E group, evolocumab-treated group; non-E group, evolocumab non-treated group; OS, overall survival; HR, hazard ratio; CI, confidence interval
Fig.4. Wound-free limb salvage rate
Fig.4. Wound-free limb salvage rate
The proportion of wound-free limb salvage was analyzed in the patients with Rutherford classifications of 5 and 6 (E group, n =12, vs. non-E group, n =12). The wound-free limb salvage rate was significant higher in the E group at 12 months (E group [92%] vs. non-E group [42%]; p =0.03). E group, evolocumab-treated group; non-E group, evolocumab non-treated group
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