TY - JOUR
T1 - Hyperglycaemic disorders associated with PCSK9 inhibitors
T2 - a real-world, pharmacovigilance study
AU - Goldman, Adam
AU - Raschi, Emanuel
AU - Cukierman-Yaffe, Tali
AU - Dankner, Rachel
AU - Shouval, Roni
AU - Shechter, Michael
AU - Ben-Zvi, Ilan
AU - Gerstein, Hertzel C.
AU - Maor, Elad
N1 - Publisher Copyright:
© 2022 The Author(s).
PY - 2022/7/1
Y1 - 2022/7/1
N2 - 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.
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.
KW - Adverse events
KW - Cardiovascular disease prevention
KW - Diabetes incidence
KW - Dyslipidaemia
KW - Hyperglycaemia
KW - PCSK9 inhibitors
UR - http://www.scopus.com/inward/record.url?scp=85134854342&partnerID=8YFLogxK
U2 - 10.1093/eurjpc/zwab209
DO - 10.1093/eurjpc/zwab209
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C2 - 34897409
AN - SCOPUS:85134854342
SN - 2047-4873
VL - 29
SP - 1334
EP - 1342
JO - European Journal of Preventive Cardiology
JF - European Journal of Preventive Cardiology
IS - 9
ER -
