Evolocumab Safety and Efficacy in Hypercholesteremia Patients with or Without Diabetes: a Retrospective Real-world Analysis

Overview

Journal Diabetol Metab Syndr

Publisher Biomed Central

Date 2025 Jan 31

PMID 39891190

Authors

Sultan Ibrahim Alraddadi

Hind Almodaimegh

Abdullah Kharbosh

Hadeel Alharbi

Ahmed Ibrahim Fathelrahman

Mona Yaser Alsheikh

Lama Alfehaid

Affiliations

Soon will be listed here.

Abstract

Background: Proprotein convertase subtilisin/kexin type 9 inhibitors effectively reduce LDL cholesterol and adverse cardiovascular events with a safety profile comparable to a placebo. Limited real-world data exists on their effectiveness in different patient groups. This study evaluated evolocumab's efficacy and safety in hypercholesteremia patients with and without diabetes.

Method: In a large tertiary hospital in Saudi Arabia, patients aged 18 and above who initiated evolocumab therapy were screened for eligibility between January 2017 and July 2023. All patients who had been on maximally tolerated statin and ezetimibe therapy for at least 4 months before starting evolocumab were included. The included participants were then divided into diabetic and non-diabetic groups and assessed for evolocumab's efficacy and safety. Efficacy was measured by LDL-C reduction and target achievement, while safety was assessed by examining glycemic control changes, new-onset diabetes (NOD) and hepatic enzyme levels. Data analysis included descriptive and comparative methods, with significance set at p < 0.05.

Results: A total of 151 patients were included, with an average age of 51.77 years. The majority of patients were male (67.6%) and obese (81.5%). Around 55% had diabetes, and 63% had established atherosclerotic cardiovascular disease at baseline. During a mean follow-up period of 13.17 months, the average reduction in LDL-C from baseline was - 34.21, - 28.66, and - 39.61% for the overall cohort, non-diabetic patients, and diabetic patients, respectively. In the overall cohort, 34.4 and 24.5% reached the target LDL-C levels of less than 1.4 mmol/L (55 mg/dL) and less than 1.8 mmol/L (70 mg/dL), respectively. Worsening of glycemic control (HbA1C increase > 0.5) was observed in 25.83% of the overall cohort, 16.18% of non-diabetics, and 33.74% of diabetics. An HbA1C increase > 1 was observed in 13.25% of the overall cohort, 2.94% in non-diabetics and 21.69% in diabetics. Five patients (3.3%) developed NOD.

Conclusion: The study demonstrated that the addition of evolocumab to maximally tolerated statin and ezetimibe therapy reduced LDL-C levels but with a smaller average reduction and a lower proportion of patients achieving recommended LDL-C targets than in landmark clinical trials. Additionally, there was a potential negative effect on glycemic control, warranting further investigation.

References

Kannel W, CASTELLI W, Gordon T, MCNAMARA P . Serum cholesterol, lipoproteins, and the risk of coronary heart disease. The Framingham study. Ann Intern Med. 1971; 74(1):1-12. DOI: 10.7326/0003-4819-74-1-1. View

Stamler J, Wentworth D, Neaton J . Is relationship between serum cholesterol and risk of premature death from coronary heart disease continuous and graded? Findings in 356,222 primary screenees of the Multiple Risk Factor Intervention Trial (MRFIT). JAMA. 1986; 256(20):2823-8. View

Pearson G, Thanassoulis G, Anderson T, Barry A, Couture P, Dayan N . 2021 Canadian Cardiovascular Society Guidelines for the Management of Dyslipidemia for the Prevention of Cardiovascular Disease in Adults. Can J Cardiol. 2021; 37(8):1129-1150. DOI: 10.1016/j.cjca.2021.03.016. View

Kasichayanula S, Grover A, Emery M, Gibbs M, Somaratne R, Wasserman S . Clinical Pharmacokinetics and Pharmacodynamics of Evolocumab, a PCSK9 Inhibitor. Clin Pharmacokinet. 2018; 57(7):769-779. PMC: 5999140. DOI: 10.1007/s40262-017-0620-7. View

Sabatine M, Giugliano R, Keech A, Honarpour N, Wiviott S, Murphy S . Evolocumab and Clinical Outcomes in Patients with Cardiovascular Disease. N Engl J Med. 2017; 376(18):1713-1722. DOI: 10.1056/NEJMoa1615664. View

Schwartz G, Steg P, Szarek M, Bhatt D, Bittner V, Diaz R . Alirocumab and Cardiovascular Outcomes after Acute Coronary Syndrome. N Engl J Med. 2018; 379(22):2097-2107. DOI: 10.1056/NEJMoa1801174. View

Ference B, Robinson J, Brook R, Catapano A, Chapman M, Neff D . Variation in PCSK9 and HMGCR and Risk of Cardiovascular Disease and Diabetes. N Engl J Med. 2016; 375(22):2144-2153. DOI: 10.1056/NEJMoa1604304. View

Swerdlow D, Preiss D, Kuchenbaecker K, Holmes M, Engmann J, Shah T . HMG-coenzyme A reductase inhibition, type 2 diabetes, and bodyweight: evidence from genetic analysis and randomised trials. Lancet. 2014; 385(9965):351-61. PMC: 4322187. DOI: 10.1016/S0140-6736(14)61183-1. View

Goldman A, Raschi E, Cukierman-Yaffe T, Dankner R, Shouval R, Shechter M . Hyperglycaemic disorders associated with PCSK9 inhibitors: a real-world, pharmacovigilance study. Eur J Prev Cardiol. 2021; 29(9):1334-1342. DOI: 10.1093/eurjpc/zwab209. View

10.

Lehrke M, Vogt A, Schettler V, Girndt M, Fraass U, Tabbert-Zitzler A . Evolocumab-Based LDL-C Management in High and Very High Cardiovascular Risk Patients in German Clinical Practice: The HEYMANS Study. Adv Ther. 2024; 41(3):1184-1200. PMC: 10879337. DOI: 10.1007/s12325-023-02757-x. View

11.

Gupta M, Mancini G, Wani R, Ahooja V, Bergeron J, Manjoo P . Real-World Insights Into Evolocumab Use in Patients With Hyperlipidemia: Canadian Analysis From the ZERBINI Study. CJC Open. 2022; 4(6):558-567. PMC: 9207771. DOI: 10.1016/j.cjco.2022.03.003. View

12.

Al Faraidy K, Akbar M, Shehri M, Aljarallah M, Abdin Hussein G, Dashti R . Multizonal observational study conducted by clinical practitioners on evolocumab use in subjects with hyperlipidemia in Saudi Arabia and Kuwait: Results from the ZERBINI study. PLoS One. 2023; 18(1):e0278821. PMC: 9858091. DOI: 10.1371/journal.pone.0278821. View

13.

de Carvalho L, Campos A, Sposito A . Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9) Inhibitors and Incident Type 2 Diabetes: A Systematic Review and Meta-analysis With Over 96,000 Patient-Years. Diabetes Care. 2017; 41(2):364-367. DOI: 10.2337/dc17-1464. View

14.

Carugo S, Sirtori C, Corsini A, Tokgozoglu L, Ruscica M . PCSK9 Inhibition and Risk of Diabetes: Should We Worry?. Curr Atheroscler Rep. 2022; 24(12):995-1004. PMC: 9750910. DOI: 10.1007/s11883-022-01074-y. View

15.

Giugliano R, Pedersen T, Park J, De Ferrari G, Gaciong Z, Ceska R . Clinical efficacy and safety of achieving very low LDL-cholesterol concentrations with the PCSK9 inhibitor evolocumab: a prespecified secondary analysis of the FOURIER trial. Lancet. 2017; 390(10106):1962-1971. DOI: 10.1016/S0140-6736(17)32290-0. View

16.

Sabatine M, Leiter L, Wiviott S, Giugliano R, Deedwania P, De Ferrari G . Cardiovascular safety and efficacy of the PCSK9 inhibitor evolocumab in patients with and without diabetes and the effect of evolocumab on glycaemia and risk of new-onset diabetes: a prespecified analysis of the FOURIER randomised controlled trial. Lancet Diabetes Endocrinol. 2017; 5(12):941-950. DOI: 10.1016/S2213-8587(17)30313-3. View

17.

ODonoghue M, Giugliano R, Wiviott S, Atar D, Keech A, Kuder J . Long-Term Evolocumab in Patients With Established Atherosclerotic Cardiovascular Disease. Circulation. 2022; 146(15):1109-1119. DOI: 10.1161/CIRCULATIONAHA.122.061620. View

18.

Mach F, Baigent C, Catapano A, Koskinas K, Casula M, Badimon L . 2019 ESC/EAS Guidelines for the management of dyslipidaemias: lipid modification to reduce cardiovascular risk. Eur Heart J. 2019; 41(1):111-188. DOI: 10.1093/eurheartj/ehz455. View

18.

Gonzalez-Lleo A, Sanchez-Hernandez R, Plana N, Ibarretxe D, Rehues P, Ribalta J . Impact of PCSK9 inhibitors in glycaemic control and new-onset diabetes. Cardiovasc Diabetol. 2024; 23(1):4. PMC: 10765818. DOI: 10.1186/s12933-023-02077-y. View