Lipid-lowering therapy with PCSK9-inhibitors in the real-world setting: Two-year experience of a regional lipid clinic

Abstract A real-world setting study of familial hypercholesterolemia (FH) patients who received Proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors in a specialized referral center in Mexico City. Ten patients between the ages of 18 and 70 years, with a diagnosis of FH according to Dutch Lipid Clinic Network (DLCN) criteria, with failure to achieve their Low-density lipoprotein Cholesterol (LDL-C) goals, and with standard therapy between 2016 and 2017 enrolled in a simple randomization in which a group of 5 participants received alirocumab (75 mg every 2 weeks) and the remaining 5 patients received evolocumab (140 mg every 2 weeks). Comparative analysis was made, analyzing the means of LDL at baseline at 4, 6, and 12 weeks. The evolocumab group had an average initial LDL-C of 277 mg/dL, which, after 12 weeks of treatment, was significantly reduced to 116 mg/dL; P = 0.04 (95% confidence interval [CI]: 11.5–310.9). The alirocumab group with a mean initial LDL-C of 229 mg/dL showed a reduction of LDL-C levels at 12 weeks of treatment to 80 mg/dL; P = 0.008 (95% CI: 63.8–233.7). In conclusion, PCSK9 inhibitors are an excellent treatment option in patients with FH who do not reach their LDL-C goals with standard therapy or due to intolerance to the standard therapy. There is no difference in the lipid-lowering effect between both PSCK9 inhibitors.

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PCSK9 Inhibitors in Clinical Practice: Experience of a Specialized Lipid Center

Rational Pharmacotherapy in Cardiology ◽

10.20996/1819-6446-2021-12-01 ◽

2022 ◽

Vol 17 (6) ◽

pp. 808-815

Author(s):

A. V. Blokhina ◽

A. I. Ershova ◽

A. S. Limonova ◽

O. V. Kopylova ◽

A. N. Meshkov ◽

...

Keyword(s):

High Intensity ◽

Low Density Lipoprotein ◽

Density Lipoprotein ◽

Lipid Lowering ◽

Lipid Lowering Therapy ◽

Pcsk9 Inhibitors ◽

Lipid Clinic ◽

Lowering Therapy ◽

Lipid Metabolism Disorders ◽

Very High

Aim. To characterize patients receiving PCSK9 inhibitors, and assess the efficiency of their treatment in a specialized lipid center.Material and methods. A retrospective analysis of the medical records of patients who visited the Lipid clinic of the National Medical Research Center for Therapy and Preventive Medicine (Moscow, Russia), receiving PCSK9 inhibitor and having lipid profile in dynamics, was carried out (n=77). Cardiovascular risk (CVR) and low-density lipoprotein cholesterol (LDL-C) target levels were evaluated in accordance with the Russian guidelines for the diagnostics and correction of dyslipidemias 2020.Results. Of 77 patients taking PCSK9 inhibitors (44.2% males, the median of age 56 [47; 66] years), the majority (64.0%) had a probable or definite familial hypercholesterolemia (FH). The proportion of other lipid metabolism disorders, pure hypercholesterolemia and combined hyperlipidemia was 21% and 15%. More than half of the patients (68.8%) had a very high CVR, mainly due to the presence of coronary heart disease (84.9%). The proportion of patients receiving PCSK9 inhibitors as monotherapy was 7.8%, in combination with high-intensity statin therapy – 33.8%, as part of triple lipid-lowering therapy (high-intensity statin, ezetimibe, PCSK9 inhibitors) – 50.6%. Addition of PCSK9 inhibitors to combined lipid-lowering therapy enabled to reduce the LDL-C level to 1.02 [0.62; 1.39] mmol/l with its total decrease from the baseline by 87.3%. While taking PCSK9 inhibitors, LDL-C <1.8 mmol/l and <1.4 mmol/l achieved at 78.3% and 57.7% FH patients with high and very high CVR, respectively. Among patients with other hyperlipidemias, 74.1% of patients with very high CVR was achieved the target LDL-C level <1.4 mmol/l.Conclusion: In a specialized lipid center, PCSK9 inhibitors are prescribed to patients with high or very high CVR, most of whom are FH patients. The effectiveness of the use of PCSK9 inhibitors in real-world practice is comparable to the results of clinical trials.

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Application of the 2019 ESC/EAS dyslipidaemia guidelines to nationwide data of patients with a recent myocardial infarction: a simulation study

European Heart Journal ◽

10.1093/eurheartj/ehaa034 ◽

2020 ◽

Vol 41 (40) ◽

pp. 3900-3909 ◽

Cited By ~ 8

Author(s):

Ali Allahyari ◽

Tomas Jernberg ◽

Emil Hagström ◽

Margrét Leosdottir ◽

Pia Lundman ◽

...

Keyword(s):

Myocardial Infarction ◽

High Intensity ◽

Low Density Lipoprotein ◽

Monte Carlo Model ◽

Density Lipoprotein ◽

Lipid Lowering ◽

Lipid Lowering Therapy ◽

Pcsk9 Inhibitors ◽

Recent Myocardial Infarction ◽

Lowering Therapy

Abstract Aims To estimate the proportion of patients with a recent myocardial infarction (MI) who would be eligible for additional lipid-lowering therapy according to the 2019 European Society of Cardiology (ESC)/European Atherosclerosis Society (EAS) guidelines for the management of dyslipidaemias, and to simulate the effects of expanded lipid-lowering therapy on attainment of the low-density lipoprotein cholesterol (LDL-C) target as recommended by the guidelines. Methods and results Using the nationwide SWEDEHEART register, we included 25 466 patients who had attended a follow-up visit 6–10 weeks after an MI event, 2013–17. While most patients (86.6%) were receiving high-intensity statins, 82.9% of the patients would be eligible for expanded lipid-lowering therapy, as they had not attained the target of an LDL-C level of <1.4 mmol and a ≥50% LDL-C level reduction. When maximized use of high-intensity statins followed by add-on therapy with ezetimibe was simulated using a Monte Carlo model, the LDL-C target was reached in 19.9% using high-intensity statin monotherapy and in another 28.5% with high-intensity statins and ezetimibe, while 50.7% would still be eligible for proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors. When use of alirocumab or evolocumab was simulated in those who were eligible for PCSK9 inhibitors, around 90% of all patients attained the LDL-C target. Conclusion Our study suggests that, even with maximized use of high-intensity statins and ezetimibe, around half of patients with MI would be eligible for treatment with PCSK9 inhibitors according to the 2019 ESC/EAS guidelines. Considering the current cost of PCSK9 inhibitors, the financial implications of the new guidelines may be substantial.

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History of Lipid Lowering Therapy and Cardiovascular Medication Use Among Patients Initiating PCSK9 Inhibitors in the United States

Value in Health ◽

10.1016/j.jval.2018.04.402 ◽

2018 ◽

Vol 21 ◽

pp. S67-S68

Author(s):

RL Wade ◽

DM Hines ◽

PB Rane ◽

J Patel ◽

DJ Harrison

Keyword(s):

United States ◽

Medication Use ◽

The United States ◽

Lipid Lowering ◽

Lipid Lowering Therapy ◽

Pcsk9 Inhibitors ◽

Cardiovascular Medication ◽

Lowering Therapy ◽

History Of

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Incremental net benefit of lipid-lowering therapy with PCSK9 inhibitors: a systematic review and meta-analysis of cost-utility studies

European Journal of Clinical Pharmacology ◽

10.1007/s00228-021-03242-6 ◽

2021 ◽

Author(s):

Bhavani Shankara Bagepally ◽

Akhil Sasidharan

Keyword(s):

Systematic Review ◽

Meta Analysis ◽

Cost Utility ◽

Lipid Lowering ◽

Lipid Lowering Therapy ◽

Net Benefit ◽

Pcsk9 Inhibitors ◽

Lowering Therapy ◽

Incremental Net Benefit

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Lipid Clinic is an Efficacious Model of Preventive Medicine

Rational Pharmacotherapy in Cardiology ◽

10.20996/1819-6446-2021-01-02 ◽

2021 ◽

Vol 17 (1) ◽

pp. 4-10

Author(s):

A. V. Blokhina ◽

A. I. Ershova ◽

A. N. Meshkov ◽

A. S. Limonova ◽

V. I. Mikhailina ◽

...

Keyword(s):

Lipid Metabolism ◽

Preventive Medicine ◽

Medical Center ◽

Lipid Lowering ◽

Lipid Lowering Therapy ◽

Medical Care System ◽

Lipid Clinic ◽

Lowering Therapy ◽

Target Values ◽

Very High

Aim. To characterize patients accessing lipid clinic and assess the efficiency of treatment in a specialized medical center.Material and methods. A retrospective analysis of the surviving medical records of outpatients who visited the lipid clinic of the National Research Center for Therapy and Preventive Medicine (Moscow, Russia) in 2011-2019 (n=675) was carried out. Cardiovascular risk (CVR) and target lipoproteins levels were evaluated in accordance with actual guidelines for the diagnostics and correction of dyslipidemias.Results. The mediana of lipid clinic patients age was 57 [46;65] years. Female persons attend lipid clinic more often (61.5%). 48.5% of patients had low density lipoprotein cholesterol (LDL-c) >4.9 mmol/L, 7.7% had triglycerides level >5.5 mmol/L. Most of the patients were diagnosed with type IIa hyperlipidemia (44,1%) or type IIb (28,0%). Inherited impaired lipid metabolism was diagnosed in 27.7% individuals. 12.7% of the patients had familial hypercholesterolemia, 57.4% – had secondary causes of impaired lipid metabolism. More than half of the patients (52.4%) had low or moderate CVR, 28.1% had a very high CVR. High or very high CVR individuals revisited the lipid clinic more often than people with lower risk (68.2% vs. 35.4%). Revisiting patients (25.4%) reached LDL-c targets more often (33.3% of very high CVR patients; 45.5% of moderate-risk people) than in ordinary outpatient practice. High-intensity statin therapy was recommended for 32% of patients, and combined lipid-lowering therapy – for 14.8%. Among very high CVR individuals, combined lipid-lowering therapy was prescribed for 38.5%. Given the lipid-lowering therapy prescribed in the lipid clinic, LDL-с<1.8 mmol/L and<1.5 mmol/L will be achieved at 40.7% and 32.9% of patients with very high СVR.Conclusion. Lipid clinic is an important part of the medical care system for long-term follow-up of patients with impaired lipid metabolism, and it is more efficient in achieving target values of lipids and correcting risk factors in comparison with the primary medical service.

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Intensification of lipid-lowering therapy in patients with severe lipid metabolism disorders in specialized lipid control centers. Possibilities of using evolocumab

Russian Medical Inquiry ◽

10.32364/2587-6821-2020-4-7-437-444 ◽

2020 ◽

Vol 4 (7) ◽

pp. 437-444

Author(s):

O.L. Barbarash ◽

◽

V.V. Kashtalap ◽

N.V. Fedorova ◽

D.Yu. Sedykh ◽

...

Keyword(s):

Lipid Metabolism ◽

Current Data ◽

Lipid Lowering ◽

Lipid Lowering Therapy ◽

Pcsk9 Inhibitors ◽

Control Center ◽

Lowering Therapy ◽

Lipid Metabolism Disorders ◽

Target Values ◽

Lipid Control

The article presents current data on the prevalence of dyslipidemia worldwide and in the Russian Federation as the main cardiovascular risk factor of developing diseases associated with atherosclerosis. The article identifies the problems of low-level detection of dyslipidemia in the population and insufficient efficacy of lipid-lowering therapy to achieve the lipid profile target values depending on the established risk. It also presents the possibilities of modern lipid-lowering therapy with the use of innovative drugs — PCSK9 inhibitors and the use of evolocumab in accordance with evidence-based medicine. Adding that, the article shows the experience of two lipid control centers (in Kemerovo and Surgut) with the postulation of the need to expand the lipid control center chain to improve methods for providing medical care to patients with severe forms of dyslipidemia. The possibilities of intensifying lipid-lowering therapy in real clinical practice are outlined on the example of patients undergoing treatment in the lipid control center of Kemerovo. Evolocumab has been shown to be highly effective: reduction of atherogenic cholesterol fractions by 67% from the baseline and high safety of such therapy.KEYWORDS: lipid metabolism disorders, statins, lipid-lowering therapy, familial hypercholesterolemia, PCSK9 inhibitors, evolocumab.FOR CITATION: Barbarash O.L., Kashtalap V.V., Fedorova N.V. et al. Intensification of lipid-lowering therapy in patients with severe lipid metabolism disorders in specialized lipid control centers. Possibilities of using evolocumab. Russian Medical Inquiry. 2020;4(7):437–444. DOI: 10.32364/2587-6821-2020-4-7-437-444.

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The current LDL-C target <1.4mmol/l of the ESC is achieved in less than 16% of patients with Coronary Heart Disease despite effective lipid-lowering therapy: data from the LLT-R registry

European Heart Journal ◽

10.1093/ehjci/ehaa946.2998 ◽

2020 ◽

Vol 41 (Supplement_2) ◽

Author(s):

F Noack ◽

B Schwaab ◽

H Voeller ◽

K Eckrich ◽

M Guha ◽

...

Keyword(s):

Coronary Heart Disease ◽

Heart Disease ◽

Cardiac Rehabilitation ◽

Lipid Lowering ◽

Funding Source ◽

Lipid Lowering Therapy ◽

Pcsk9 Inhibitors ◽

Lowering Therapy ◽

Rehabilitation Clinic

Abstract Background In the current guideline of the ESC, in patients with very high cardiovascular risk such as coronary heart disease (CHD) a treatment target for LDL-C <1.4mmol/l and/or a halving of the initial value are defined. It is unclear whether these treatment targets are achievable with standard therapy including statins and/or ezetemibe. Methods The primary objective of this prospective, multi-centre register study was the question of the guidance-based adaptation and adherence to lipid-lowering therapy during and after a cardiac rehabilitation in 1,100 patients with CHD up to 12 months after discharge from the six rehabilitation clinics involved. Patients were included from 2016 to 2018. Results The median age of the 1,100 patients was 63.4±10.4 years, the mean BMI was 28.5±4.7kg/m2, and 24.1% of patients were female. 12.2% were active smokers, 91.6% reported dyslipoproteinemia, 33.9% suffered from diabetes mellitus and 86.5% from hypertension. The majority of patients were included with the main indications NSTEMI (31.6%), STEMI (29.6%) and after CABG surgery (26.4%). The proportion of patients treated with statins was more than 94% when admitted and discharged from the rehabilitation clinic, as well as in 3- and 12-months follow-ups. Approximately 9% of patients were treated with ezetemibe at baseline. On discharge from the rehabilitation clinic 23% of patients were treated with ezetemibe, which remains stable at 3 and 12 months. PCSK9 inhibitors were used in 0.1–0.3% of patients at all times. The adjustment of LLT during three week cardiac rehabilitation resulted in median LDL-C values of 2.27mmol/l (1.80/2.84) at baseline, 1.97mmol/l (1.57/2.47) on discharge (p<0.001 compared to baseline), 1.94mmol/l (1.57/2.49) after three months and 1.94mmol/l (1.53/2.40) after 12 months. The proportion of patients with LDL-C <1.4mmol/l was 9% at baseline, 15.7% on discharge (p<0.001 compared to baseline), 15.6% at three-month follow-up and 15.1% at 12-month follow-up (Figure 1). Discussion In the context of cardiac rehabilitation, an effective adjustment of LLT is carried out, which resulted in a significant reduction of LDL-C. However, despite a high percentage of patients on statins and ezetemibe, the proportion of patients in the new target range <1.4mmol/l was only achievable in a small percentage and the question arises whether these treatment targets can be achieved without additional administration of PCSK9 inhibitors in majority of patients with CHD. Figure 1 Funding Acknowledgement Type of funding source: Private company. Main funding source(s): This study was supported by an unrestricted grant from Sanofi-Aventis Germany.

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Statins and PCSK9 inhibitors: A new lipid-lowering therapy

European Journal of Pharmacology ◽

10.1016/j.ejphar.2020.173114 ◽

2020 ◽

Vol 878 ◽

pp. 173114 ◽

Cited By ~ 1

Author(s):

Enrique Gallego-Colon ◽

Aner Daum ◽

Chaim Yosefy

Keyword(s):

Lipid Lowering ◽

Lipid Lowering Therapy ◽

Pcsk9 Inhibitors ◽

Lowering Therapy

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