PMID- 37773882
OWN - NLM
STAT- MEDLINE
DCOM- 20231005
LR  - 20231005
IS  - 1558-2035 (Electronic)
IS  - 1558-2027 (Linking)
VI  - 24
IP  - 11
DP  - 2023 Nov 1
TI  - Major cardiovascular events increase in long-term proprotein convertase 
      subtilisin/kexin type 9 inhibitors therapy: the Tuscany cost-effective study.
PG  - 808-814
LID - 10.2459/JCM.0000000000001546 [doi]
AB  - BACKGROUND: Proprotein convertase subtilisin/kexin type 9 inhibitors (PCSK9i) 
      represent a breakthrough in the treatment of hypercholesterolemia. The aim of 
      this study was to perform a multicentre prospective analysis on the effects of 
      PCSK9i since their distribution in Italy. METHODS: During the study period (July 
      2017 to February 2022) 246 patients (mean age 61 +/- 11 years, male 73%) who were 
      evolocumab (142/246) or alirocumab (104/246) new users were enrolled in the CERTI 
      (Costo Efficacia Regione Toscana Inibitori PCSK9) study. Lipid value, adverse 
      events (AEs), major cardiovascular events (MACEs) and intima-media thickness were 
      analysed. RESULTS: PCSK9i therapy allowed a significant improvement in patients' 
      lipid profile [total cholesterol -35%, P < 0.001; triglycerides -9%, P < 0.05; 
      low-density lipoprotein (LDL) cholesterol -51%, P < 0.001; Lp(a) levels -4%, 
      P < 0.05], maintained during the follow-up. No significant variations in 
      intima-media thickness were observed. In the subgroup of patients with more than 
      1 year of PCSK9i therapy (165/246 patients) we highlighted: a 66% reduction in 
      MACEs compared with the year before recruitment; a progressive increase in MACEs 
      during the follow-up (MACEs event/rate at first year 0.08 vs. MACEs event/rate at 
      year 5: 0.47); a patients cluster with late MACEs older, with higher prevalence 
      of hypertension, smoking habit and peripheral vascular disease. During the 
      follow-up, we recorded AEs in 31% of patients, which mainly resulted in 
      reduction/discontinuation of lipid-lowering therapy for 50 patients or in 
      discontinuation/shift of PCSK9i (respectively 8 and 6 cases). CONCLUSION: Our 
      data agree with the large evidence on the effectiveness/tolerability of PCSK9i 
      therapy; however, although PCSK9i represents a good cholesterol-lowering 
      therapeutic option, our study shows a progressive increase in MACEs during the 
      late follow-up that deserve further research.
CI  - Copyright (c) 2023 Italian Federation of Cardiology - I.F.C. All rights reserved.
FAU - Sbrana, Francesco
AU  - Sbrana F
AD  - UO Lipoapheresis and Center for Inherited Dyslipidemias, Fondazione Toscana 
      Gabriele Monasterio, Pisa.
FAU - Dal Pino, Beatrice
AU  - Dal Pino B
AD  - UO Lipoapheresis and Center for Inherited Dyslipidemias, Fondazione Toscana 
      Gabriele Monasterio, Pisa.
FAU - Bigazzi, Federico
AU  - Bigazzi F
AD  - UO Lipoapheresis and Center for Inherited Dyslipidemias, Fondazione Toscana 
      Gabriele Monasterio, Pisa.
FAU - Ripoli, Andrea
AU  - Ripoli A
AD  - UO Lipoapheresis and Center for Inherited Dyslipidemias, Fondazione Toscana 
      Gabriele Monasterio, Pisa.
FAU - Corciulo, Carmen
AU  - Corciulo C
AD  - UO Lipoapheresis and Center for Inherited Dyslipidemias, Fondazione Toscana 
      Gabriele Monasterio, Pisa.
FAU - Lo Surdo, Giuseppa
AU  - Lo Surdo G
AD  - UOC Farmacia Ospedaliera, Fondazione Toscana Gabriele Monasterio, Massa, Italy.
FAU - Biagini, Stefania
AU  - Biagini S
AD  - UOC Farmacia Ospedaliera, Fondazione Toscana Gabriele Monasterio, Massa, Italy.
FAU - Sampietro, Tiziana
AU  - Sampietro T
AD  - UO Lipoapheresis and Center for Inherited Dyslipidemias, Fondazione Toscana 
      Gabriele Monasterio, Pisa.
CN  - CERTI study Group
LA  - eng
PT  - Journal Article
PT  - Multicenter Study
DEP - 20230929
PL  - United States
TA  - J Cardiovasc Med (Hagerstown)
JT  - Journal of cardiovascular medicine (Hagerstown, Md.)
JID - 101259752
RN  - 0 (Anticholesteremic Agents)
RN  - 0 (Cholesterol, LDL)
RN  - 0 (PCSK9 Inhibitors)
RN  - EC 3.4.21.- (PCSK9 protein, human)
RN  - EC 3.4.21.- (Proprotein Convertase 9)
RN  - EC 3.4.21.- (Subtilisins)
SB  - IM
MH  - Aged
MH  - Humans
MH  - Male
MH  - Middle Aged
MH  - *Anticholesteremic Agents/adverse effects
MH  - *Cardiovascular Diseases/chemically induced
MH  - Carotid Intima-Media Thickness
MH  - Cholesterol, LDL
MH  - Cost-Benefit Analysis
MH  - PCSK9 Inhibitors
MH  - Proprotein Convertase 9
MH  - Subtilisins
EDAT- 2023/09/29 18:42
MHDA- 2023/10/02 06:42
CRDT- 2023/09/29 15:44
PHST- 2023/10/02 06:42 [medline]
PHST- 2023/09/29 18:42 [pubmed]
PHST- 2023/09/29 15:44 [entrez]
AID - 01244665-202311000-00006 [pii]
AID - 10.2459/JCM.0000000000001546 [doi]
PST - ppublish
SO  - J Cardiovasc Med (Hagerstown). 2023 Nov 1;24(11):808-814. doi: 
      10.2459/JCM.0000000000001546. Epub 2023 Sep 29.