Analysis of the efficacy of alirocumab genetically engineered therapy in patients with very high cardiovascular risk, with and without diabetes mellitus: A prospective registry study
Background. In very high cardiovascular risk (CVR) patients with concomitant diabetes mellitus (DM), the achieving target levels of atherogenic lipids while undergoing standard lipid-lowering therapy remains to be an unresolved problem, necessitating the study of the efficacy of PCSK9 inhibitors in real clinical practice. Objective: To evaluate the dynamics of achieving target level of cholesterol by low-density lipoproteins (LDL-C H <1.4 mmol/L) and triglycerides (TG <1.7 mmol/L) in real clinical practice with alirocumab therapy in patients with very high CVR with and without DM. Material and methods. A total of 299 patients with very high CVR, including 103 (34%) with DM, were consecutively included in the prospective, single-center observational study. All the participants received alirocumab 300 mg subcutaneously every 4 weeks, with underlying failure to achieve the target LDL-CH level (<1.4 mmol/L) with maximally tolerated lipid-lowering therapy or in cases of statin intolerance. Laboratory monitoring of the lipid profile was performed monthly for 21 visit. Results. The baseline LDL-CH level in the group of patients with DM was 3.15 [2.20–4.05] mmol/L, in the group without DM – 2.95 [1.95–3.85] mmol/L (in the overall cohort – 3.01 [2.03–3.90] mmol/L). By visit 21, 46.2% (95% confidence interval (CI): 37.2–55.4) of patients with DM and 53.7% (95% CI: 46.9–60.4%) without DM had achieved LDL-CH target values (χ² = 1.08, p = 0.299). The frequency of achieving TG target values was 64.5% (95% CI: 55.2–72.7) in patients with DM versus 78.0% (95% CI: 72.0–83.1) in participants without DM (χ² = 4.58, p = 0.032). Trend analysis revealed no significant monotonic change in the efficacy of alirocumab in terms of LDL-CH in either group (DM: ρ = 0.11, p = 0.64; without DM: ρ = -0.09, p = 0.71), indicating stabilization of the treatment effect after reaching a plateau. Conclusion. The addition of alirocumab to lipid-lowering therapy ensured a sustained reduction in LDL-CH in patients with very high CVR, regardless of the presence of DM. The target TG level was achieved in most patients, regardless of the presence of diabetes: in 64.5% (95% CI: 55.2–72.7%) of cases in the DM group and in 78.0% (95% CI: 72.0–83.1%) in the non-DM group (p = 0.032). However, the presence of DM is associated with a significantly lower rate of normalization of triglyceride levels, necessitating additional attention to complex lipid correction in this subgroup of patients. Obtained data support the advisability of early inclusion of PCSK9 inhibitors in the management algorithms for patients who fail to achieve target values with standard lipid-lowering therapy performing.I.V. Petrenko, O.M. Reitblat, D.R. Bulatova, A.V. Khristolyubova
Keywords
atherosclerosis
alirocumab
proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor
diabetes mellitus
low-density lipoprotein cholesterol
triglycerides
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About the Authors
Igor V. Petrenko, MD, PhD (Medicine), head of the Cardiology Center, Multidisciplinary Consultative and Diagnostic Center, Tyumen, Russian Federation.E-mail: ivp3004@mail.ru
ORCID: https://orcid.org/0000-0003-1352-9504
Oleg M. Reitblat, MD, PhD (Medicine), head of the Regional Vascular Center, Regional Clinical Hospital No. 1, Tyumen, Russian Federation.
E-mail: reitblat111@mail.ru
ORCID: https://orcid.org/0000-0002-9407-5497
Dinara R. Bulatova, MD, head of the Mobile Medical Center, Multidisciplinary Consultative and Diagnostic Center, Tyumen, Russian Federation.
E-mail: bdr84@yandex.ru
ORCID: https://orcid.org/0009-0007-6036-0429
Anastasia V. Khristolyubova, MD, head of the Department of cardiology No. 1, Regional Clinical Hospital No. 1, Tyumen, Russian Federation.
E-mail: cardioanastasiya@gmail.com
ORCID: https://orcid.org/0009-0000-4382-1472
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