PMID- 37093712
OWN - NLM
STAT- MEDLINE
DCOM- 20230809
LR  - 20231006
IS  - 1477-0377 (Electronic)
IS  - 1358-863X (Print)
IS  - 1358-863X (Linking)
VI  - 28
IP  - 4
DP  - 2023 Aug
TI  - Alirocumab and plaque volume, calf muscle blood flow, and walking performance in 
      peripheral artery disease: A randomized clinical trial.
PG  - 282-289
LID - 10.1177/1358863X231169324 [doi]
AB  - BACKGROUND: The distal superficial femoral artery (SFA) is most commonly affected 
      in peripheral artery disease (PAD). The effects of the proprotein convertase 
      subtilisin/kexin type 9 (PCSK9) inhibitor alirocumab added to statin therapy on 
      SFA atherosclerosis, downstream flow, and walking performance are unknown. 
      METHODS: Thirty-five patients with PAD on maximally tolerated statin therapy were 
      recruited. Patients were randomized to alirocumab 150 mg subcutaneously (n = 18) 
      or matching placebo (n = 17) therapy every 2 weeks for 1 year. The primary 
      outcome was change in SFA plaque volume by black blood magnetic resonance imaging 
      (MRI). Secondary outcomes were changes in calf muscle perfusion by cuff/occlusion 
      hyperemia arterial spin labeling MRI, 6-minute walk distance (6MWD), low-density 
      lipoprotein (LDL) cholesterol, and other biomarkers. RESULTS: Age (mean +/- SD) was 
      64 +/- 8 years, 20 (57%) patients were women, 17 (49%) were Black individuals, LDL 
      was 107 +/- 36 mg/dL, and the ankle-brachial index 0.71 +/- 0.20. The LDL fell more 
      with alirocumab than placebo (mean [95% CI]) (-49.8 [-66.1 to -33.6] vs -7.7 
      [-19.7 to 4.3] mg/dL; p < 0.0001). Changes in SFA plaque volume and calf 
      perfusion showed no difference between groups when adjusted for baseline (+0.25 
      [-0.29 to 0.79] vs -0.04 [-0.47 to 0.38] cm(3); p = 0.37 and 0.22 [-8.67 to 9.11] 
      vs 3.81 [-1.45 to 9.08] mL/min/100 g; p = 0.46, respectively), nor did 6MWD. 
      CONCLUSION: In this exploratory study, the addition of alirocumab therapy to 
      statins did not alter SFA plaque volume, calf perfusion or 6MWD despite 
      significant LDL lowering. Larger studies with longer follow up that include 
      plaque characterization may improve understanding of the effects of intensive 
      LDL-lowering therapy in PAD (ClinicalTrials.gov Identifier: NCT02959047).
FAU - Rrapo-Kaso, Elona
AU  - Rrapo-Kaso E
AD  - Department of Medicine, Cardiovascular Division, University of Virginia Health, 
      Charlottesville, VA, USA.
FAU - Loffler, Adrian I
AU  - Loffler AI
AD  - Department of Medicine, Cardiovascular Division, University of Virginia Health, 
      Charlottesville, VA, USA.
FAU - Petroni, Gina R
AU  - Petroni GR
AD  - Departments of Public Health Sciences, University of Virginia Health, 
      Charlottesville, VA, USA.
FAU - Meyer, Craig H
AU  - Meyer CH
AD  - Department of Biomedical Engineering, University of Virginia Health, 
      Charlottesville, VA, USA.
AD  - Department of Radiology and Medical Imaging, University of Virginia Health, 
      Charlottesville, VA, USA.
FAU - Walker, McCall
AU  - Walker M
AD  - Department of Medicine, Cardiovascular Division, University of Virginia Health, 
      Charlottesville, VA, USA.
FAU - Kay, Jennifer R
AU  - Kay JR
AD  - Department of Radiology and Medical Imaging, University of Virginia Health, 
      Charlottesville, VA, USA.
FAU - DiMaria, Joseph M
AU  - DiMaria JM
AD  - Department of Radiology and Medical Imaging, University of Virginia Health, 
      Charlottesville, VA, USA.
FAU - Domanchuk, Kathyrn
AU  - Domanchuk K
AD  - Department of Medicine, Northwestern University, Chicago, IL, USA.
FAU - Carr, James C
AU  - Carr JC
AD  - Department of Medicine, Northwestern University, Chicago, IL, USA.
AD  - Department of Radiology, Northwestern University, Chicago, IL, USA.
FAU - McDermott, Mary M
AU  - McDermott MM
AUID- ORCID: 0000-0002-3724-7619
AD  - Department of Medicine, Northwestern University, Chicago, IL, USA.
FAU - Kramer, Christopher M
AU  - Kramer CM
AUID- ORCID: 0000-0003-2057-7731
AD  - Department of Medicine, Cardiovascular Division, University of Virginia Health, 
      Charlottesville, VA, USA.
AD  - Department of Radiology and Medical Imaging, University of Virginia Health, 
      Charlottesville, VA, USA.
LA  - eng
SI  - ClinicalTrials.gov/NCT02959047
GR  - R01 HL075792/HL/NHLBI NIH HHS/United States
GR  - T32 EB003841/EB/NIBIB NIH HHS/United States
PT  - Journal Article
PT  - Randomized Controlled Trial
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20230424
PL  - England
TA  - Vasc Med
JT  - Vascular medicine (London, England)
JID - 9610930
RN  - PP0SHH6V16 (alirocumab)
RN  - EC 3.4.21.- (PCSK9 protein, human)
RN  - EC 3.4.21.- (Proprotein Convertase 9)
RN  - 0 (Hydroxymethylglutaryl-CoA Reductase Inhibitors)
RN  - 0 (Antibodies, Monoclonal)
RN  - 0 (Cholesterol, LDL)
SB  - IM
MH  - Humans
MH  - Female
MH  - Middle Aged
MH  - Aged
MH  - Male
MH  - Proprotein Convertase 9/therapeutic use
MH  - *Hydroxymethylglutaryl-CoA Reductase Inhibitors/adverse effects
MH  - Antibodies, Monoclonal/adverse effects
MH  - Cholesterol, LDL/therapeutic use
MH  - *Plaque, Atherosclerotic/chemically induced/drug therapy
MH  - *Peripheral Arterial Disease/diagnostic imaging/drug therapy
MH  - Muscles
MH  - Treatment Outcome
MH  - Double-Blind Method
PMC - PMC10552651
MID - NIHMS1932778
OTO - NOTNLM
OT  - PCSK9 inhibition
OT  - atherosclerotic plaque
OT  - magnetic resonance imaging (MRI)
OT  - peripheral artery disease (PAD)
EDAT- 2023/04/24 18:42
MHDA- 2023/08/09 06:42
PMCR- 2024/08/01
CRDT- 2023/04/24 12:43
PHST- 2024/08/01 00:00 [pmc-release]
PHST- 2023/08/09 06:42 [medline]
PHST- 2023/04/24 18:42 [pubmed]
PHST- 2023/04/24 12:43 [entrez]
AID - 10.1177/1358863X231169324 [doi]
PST - ppublish
SO  - Vasc Med. 2023 Aug;28(4):282-289. doi: 10.1177/1358863X231169324. Epub 2023 Apr 
      24.