PMID- 34897409
OWN - NLM
STAT- MEDLINE
DCOM- 20220722
LR  - 20221110
IS  - 2047-4881 (Electronic)
IS  - 2047-4873 (Linking)
VI  - 29
IP  - 9
DP  - 2022 Jul 20
TI  - Hyperglycaemic disorders associated with PCSK9 inhibitors: a real-world, 
      pharmacovigilance study.
PG  - 1334-1342
LID - 10.1093/eurjpc/zwab209 [doi]
AB  - AIMS: While genetic and biological studies indicated a potential association 
      between proprotein-convertase subtilisin/kexin type 9 inhibitors (PCSK9i) and 
      hyperglycaemia, real-world data are limited. Therefore, we sought to investigate 
      this association using the FDA adverse event reporting system (FAERS). METHODS 
      AND RESULTS: The FAERS database (2015-2020) was retrospectively queried to 
      characterize reporting of hyperglycaemic adverse events (AEs) with PCSK9i. 
      Disproportionality analyses were performed using the adjusted reporting odds 
      ratio (adj.ROR), and the lower bound of the information component (IC) 95% 
      credibility interval (IC025 > 0 is deemed significant). Among 7 295 624 
      eligible patients, 71 748 reports of evolocumab and 15 976 of alirocumab were 
      identified. Compared to the full database, PCSK9i treatment was associated with 
      increased reporting of hyperglycaemic AEs [n = 1841, adj.ROR = 1.14 (1.07-1.22), 
      IC025 = 0.13]. Hyperglycaemic AEs were primarily mild hyperglycaemia [n = 1469, 
      adj. ROR = 1.48 (1.36-1.62), IC025 = 0.51] rather than diabetes [n = 372, adj. 
      ROR = 0.67 (0.60-0.74), IC025 = -0.90]. Among PCSK9i agents, evolocumab, but not 
      alirocumab, was associated with hyperglycaemic AEs [n = 1587, adj. ROR = 1.24 
      (1.15-1.32), IC025 = 0.20; n = 254, adj. ROR = 0.73 (0.60-0.88), IC025 = -0.38, 
      respectively]. Hyperglycaemic AEs were reported more often with PCSK9i compared 
      to ezetimibe [adj.ROR = 1.99 (1.35-2.94)], and less often compared to statins 
      [adj.ROR = 0.26 (0.25-0.28)]. Notably, hyperglycaemic AEs were reported more 
      frequently by diabetic than by non-diabetic patients (P < 0.001), mostly 
      occurred within 6 months of treatment and were reversible upon drug 
      discontinuation. CONCLUSION: In a real-world setting, PCSK9i treatment was 
      associated with increased reporting of mild hyperglycaemia, but not diabetes. 
      While initial monitoring is warranted, the favourable glycaemic safety profile 
      compared to statins supports their essential role in the management of lipid 
      disorders.
CI  - Published on behalf of the European Society of Cardiology. All rights reserved. (c) 
      The Author(s) 2021. For permissions, please email: journals.permissions@oup.com.
FAU - Goldman, Adam
AU  - Goldman A
AUID- ORCID: 0000-0001-5035-100X
AD  - Sackler Faculty of Medicine, Tel-Aviv University, Ramat Aviv, Tel Aviv 69978, 
      Israel.
AD  - Leviev Heart Center, Sheba Medical Center, Derech Sheba 2, Ramat Gan, Israel.
AD  - Department of Internal Medicine, Sheba Medical Center, Derech Sheba 2, Ramat Gan, 
      Israel.
FAU - Raschi, Emanuel
AU  - Raschi E
AD  - Pharmacology Unit, Department of Medical and Surgical Sciences, Alma Mater 
      Studiorum, University of Bologna, Bologna, Italy.
FAU - Cukierman-Yaffe, Tali
AU  - Cukierman-Yaffe T
AD  - Division of Endocrinology & Metabolism, Sheba Medical Center, Derech Sheba 2, 
      Ramat Gan, Israel.
AD  - Department of Epidemiology and Preventive Medicine, School of Public Health, 
      Sackler School of Medicine, Tel Aviv University, Ramat Aviv, Tel Aviv 69978, 
      Israel.
FAU - Dankner, Rachel
AU  - Dankner R
AUID- ORCID: 0000-0001-6454-6000
AD  - Department of Epidemiology and Preventive Medicine, School of Public Health, 
      Sackler School of Medicine, Tel Aviv University, Ramat Aviv, Tel Aviv 69978, 
      Israel.
AD  - Unit for Cardiovascular Epidemiology, The Gertner Institute for Epidemiology and 
      Health Policy Research, Sheba Medical Center, Derech Sheba 2, Ramat Gan, Israel.
FAU - Shouval, Roni
AU  - Shouval R
AD  - Adult Bone Marrow Transplantation Service, Memorial Sloan Kettering Cancer 
      Center, New York, NY, USA.
FAU - Shechter, Michael
AU  - Shechter M
AD  - Sackler Faculty of Medicine, Tel-Aviv University, Ramat Aviv, Tel Aviv 69978, 
      Israel.
AD  - Leviev Heart Center, Sheba Medical Center, Derech Sheba 2, Ramat Gan, Israel.
FAU - Ben-Zvi, Ilan
AU  - Ben-Zvi I
AD  - Sackler Faculty of Medicine, Tel-Aviv University, Ramat Aviv, Tel Aviv 69978, 
      Israel.
AD  - Department of Internal Medicine, Sheba Medical Center, Derech Sheba 2, Ramat Gan, 
      Israel.
FAU - Gerstein, Hertzel C
AU  - Gerstein HC
AD  - Population Health Research Institute, McMaster University Medical Centre-Hamilton 
      Health Sciences, Hamilton, ON, Canada.
FAU - Maor, Elad
AU  - Maor E
AD  - Sackler Faculty of Medicine, Tel-Aviv University, Ramat Aviv, Tel Aviv 69978, 
      Israel.
AD  - Leviev Heart Center, Sheba Medical Center, Derech Sheba 2, Ramat Gan, Israel.
LA  - eng
PT  - Journal Article
PL  - England
TA  - Eur J Prev Cardiol
JT  - European journal of preventive cardiology
JID - 101564430
RN  - 0 (Hydroxymethylglutaryl-CoA Reductase Inhibitors)
RN  - 0 (PCSK9 Inhibitors)
SB  - IM
CIN - Eur J Prev Cardiol. 2022 Jul 20;29(9):1331-1333. PMID: 34940857
MH  - Humans
MH  - Hydroxymethylglutaryl-CoA Reductase Inhibitors/adverse effects
MH  - *Hyperglycemia/chemically induced/diagnosis/epidemiology
MH  - *PCSK9 Inhibitors/adverse effects
MH  - Pharmacovigilance
MH  - Retrospective Studies
OTO - NOTNLM
OT  - Adverse events
OT  - Cardiovascular disease prevention
OT  - Diabetes incidence
OT  - Dyslipidaemia
OT  - Hyperglycaemia
OT  - PCSK9 inhibitors
EDAT- 2021/12/14 06:00
MHDA- 2022/07/23 06:00
CRDT- 2021/12/13 13:25
PHST- 2021/10/05 00:00 [received]
PHST- 2021/11/17 00:00 [revised]
PHST- 2021/11/24 00:00 [accepted]
PHST- 2021/12/14 06:00 [pubmed]
PHST- 2022/07/23 06:00 [medline]
PHST- 2021/12/13 13:25 [entrez]
AID - 6460198 [pii]
AID - 10.1093/eurjpc/zwab209 [doi]
PST - ppublish
SO  - Eur J Prev Cardiol. 2022 Jul 20;29(9):1334-1342. doi: 10.1093/eurjpc/zwab209.