Statins and PCSK9 inhibitors: A new lipid-lowering therapy

2020 ◽  
Vol 878 ◽  
pp. 173114 ◽  
Author(s):  
Enrique Gallego-Colon ◽  
Aner Daum ◽  
Chaim Yosefy
Keyword(s):  
Lipid Lowering ◽  
Lipid Lowering Therapy ◽  
Pcsk9 Inhibitors ◽  
Lowering Therapy

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

2020 ◽  
Vol 41 (40) ◽  
pp. 3900-3909 ◽  
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.

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

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.

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

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 &lt;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&lt;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 &lt;1.4mmol/l was 9% at baseline, 15.7% on discharge (p&lt;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 &lt;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.

scholarly journals Exposure to Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9) inhibitors and the association with neurocognitive side effects: a meta-analysis and meta-regression

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
B Hirsh-Raccah ◽  
A Yanovsky ◽  
V Rotshild ◽  
H Danenberg ◽  
R Eliaz ◽  
...  
Keyword(s):  
Side Effects ◽  
Adverse Effects ◽  
Meta Analysis ◽  
Lipid Lowering ◽  
Lipid Lowering Therapy ◽  
Proprotein Convertase ◽  
Pcsk9 Inhibitors ◽  
Lowering Therapy ◽  
Meta Regression ◽  
Meta Analyses

Abstract Background Lipid lowering therapy may be associated with impaired cognitive function. The association between the use of Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9) inhibitors and the risk of neurocognitive adverse effects remains unclear. Purpose To assess the neurocognitive safety of PCSK9 inhibitors using meta-analysis and meta-regression of randomized controlled trials (RCTs). Methods PubMed (MEDLINE), Embase and Cochrane library were searched. RCTs that reported assessments of neurocognitive outcomes of participants using PCSK9 inhibitors, with a duration of follow up of at least six months were included. The results of the search were screened by two independent reviewers. Any disagreements were resolved by consensus. The research was conducted and reported in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) extension statement for meta-analyses. Results were pooled using random-effects models. The primary safety outcome of this analysis was defined as the reported incidence of neurocognitive adverse effects. Results Results of 21 trials were included in the analysis. Among 59,733 patients, 31,611 were treated with PCSK9 inhibitors. No significant difference in the incidence of neurocognitive side effects between the treatment and control groups was identified (RR=1.01, 95% CI: 0.86–1.19, I2=3%). Same results were seen in separate analysis for each of the medicines (Alirocumab- RR=0.88, 95% CI: 0.72–1.08, I2=0%, Evolocumab- RR=1.42, 95% CI: 0.74–2.73, I2=55%). In a meta-regression analysis there was no statistically significant association between the assessed and the risk for neurocognitive side effects. Conclusions Pooled results of our meta-analysis and meta-regression clearly show that the exposure to PCSK9 inhibitors is not associated with an increased risk of neurocognitive adverse events. Due to the increasing proportion of patients using lipid-lowering therapy these results are positively reassuring. However, more data from long-term outcomes studies is needed to further evaluate the effect of longer exposure to PCSK9 inhibitors Funding Acknowledgement Type of funding source: None

scholarly journals The impact of the revised ESC Dyslipidaemia Guidelines on lipid-lowering therapy: simulating the need for PCSK9 inhibition in a contemporary ASCVD cohort

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
C Blaum ◽  
F.J Brunner ◽  
F Kroeger ◽  
J Braetz ◽  
B Bay ◽  
...  
Keyword(s):  
Lipid Lowering ◽  
Atherosclerotic Cardiovascular Disease ◽  
Lipid Lowering Therapy ◽  
Pcsk9 Inhibitors ◽  
Treatment Target ◽  
Pcsk9 Inhibitor ◽  
Lowering Therapy ◽  
Artery Disease ◽  
Pcsk9 Inhibition ◽  
The Impact

Abstract Introduction The recently updated ESC guidelines on the management of dyslipidaemias recommend a more intense LDL-cholesterol (LDL-C) reduction. For patients with atherosclerotic cardiovascular disease (ASCVD) the LDL-C goal has been revised to ≤55 mg/dl with a concomitant class IA upgrade for cost intensive PCSK9 inhibitors. Purpose We aim to quantify the need for PCSK9 inhibitors to achieve the revised LDL-C target compared to former ESC recommendations in ASCVD patients Methods We included all patients with ASCVD (angiographically documented coronary artery disease, history of peripheral artery disease or stroke) from an observational cohort study ongoing since 2015. A simulation treatment algorithm adding sequentially a high intensity statin, ezetimibe and a PCSK9 inhibitor in case of a missed treatment target was applied with consideration of both partial and total statin intolerance. The need for PCSK9 inhibitors was calculated for 3 recommendations: 1. LDL-C treatment target ≤55 mg/dl (ESC 2019 Guidelines), 2. LDL-C treatment target ≤70 mg/dl (ESC 2016 Guidelines) and 3. risk-based use of PCSK9 inhibitors restricted to patients with a residual LDL-C &gt;140 mg/dl or &gt;100 mg/dl with clinical/angiographic risk factors (ESC consensus update 2017). Results We included 1936 patients (mean age 69 years, 74% male). Median LDL-C at inclusion was 86 mg/dl, with 60% of patients taking lipid lowering medication (55% statin only, 4% statin + ezetimibe, 1% ezetimibe only). Table 1 shows the distribution of medications required to meet recommendations 1–3. After simulated stepwise intensification of lipid lowering therapy 99% of patients achieved the revised LDL-C target of ≤55 mg/dl, with a need of 23.5% for a PCSK9 inhibitor. For the former LDL-C target of ≤70 mg/dl the need for PCSK9 inhibitors was 10.5%. Restricting the use of PCSK9 inhibitors to the highest risk patients according to the ESC 2017 consensus statement reduced the need for PCSK9 inhibition to only 1.4% with slightly fewer patients achieving their LDL-C target (78% for ≤55 mg/dl and 91% for ≤70 mg/dl respectively). Conclusion The revised LDL-C treatment goals substantially increase the projected need for PCSK9 inhibitors with an unclear health economic impact. Identification of ASCVD patients with a reasonable benefit/cost-ratio of PCSK9 inhibition remains to be investigated urgently. Funding Acknowledgement Type of funding source: None

scholarly journals Effective cholesterol lowering after myocardial infarction in patients with nephrotic syndrome may require a multi-pharmacological approach: a case report

2021 ◽  
Vol 5 (5) ◽  
Author(s):  
Simon Sjuls ◽  
Ulf Jensen ◽  
Karin Littmann ◽  
Annette Bruchfeld ◽  
Jonas Brinck
Keyword(s):  
Myocardial Infarction ◽  
Nephrotic Syndrome ◽  
Sglt2 Inhibitor ◽  
Lipid Lowering ◽  
Glomerular Sclerosis ◽  
Lipid Lowering Therapy ◽  
Inhibitory Antibody ◽  
Pcsk9 Inhibitors ◽  
Focal Segmental Glomerular Sclerosis ◽  
Lowering Therapy

Abstract Background Nephrotic syndrome causes severe hypercholesterolaemia due to increased production and altered clearance of lipoproteins from the liver. It is challenging for patients with nephrotic syndrome and coronary heart disease to meet LDL-cholesterol (LDL-C) goals for secondary prevention with conventional lipid-lowering therapy. Case summary We present a man with nephrotic syndrome caused by focal segmental glomerular sclerosis (FSGS) and hypercholesterolaemia. He presented at the emergency room (ER) with an ST-elevation myocardial infarction at the age of 26. On follow-up, the patient had persistent hypercholesterolaemia [LDL-C 3.9 mmol/L and lipoprotein(a) 308 nmol/L] despite a combination of lipid-lowering therapy with atorvastatin 80 mg/day and ezetimibe 10 mg/day. Addition of the proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitory antibody evolocumab 140 mg bi-monthly did not improve cholesterol levels. However, after addition of the sodium-glucose cotransporter 2 (SGLT2) inhibitor empagliflozin 10 mg/day on top of other anti-proteinuric treatments, the patient’s proteinuria was reduced and a dramatic drop in LDL-C level by 3.2–0.6 mmol/L (−81%) was observed when evolocumab was re-introduced. Discussion We show that target LDL-C levels were obtained in this patient with therapy-resistant FSGS and hypercholesterolaemia following multi-pharmacological treatment with SGLT2 and PCSK9 inhibitors on top of conventional lipid-lowering therapy. The SGLT2-inhibitor reduced proteinuria and, speculatively, also reduced urinary loss of PCSK9-antibody. Therefore, in patients with nephrotic syndrome and cardiovascular disease novel therapeutic options to manage proteinuria could be considered to improve the efficacy of the lipid-lowering therapy, especially when the protein-based PCSK9 inhibitors are used.

scholarly journals Inclisirán as an alternative treatment for Hypercholesterolemia

2021 ◽  
Vol 12 (3) ◽  
pp. 517-521
Author(s):  
Jorge Andrés Ojeda Villota ◽  
Javier Alfredo Pérez Martínez ◽  
Luis Alberto Burgos de Moya ◽  
Rodrigo Alfonso Chavez Vega ◽  
Roxana Rivera Valencia ◽  
...  
Keyword(s):  
Risk Factors ◽  
Ldl Cholesterol ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Lipid Lowering ◽  
Lipid Lowering Therapy ◽  
Low Density ◽  
Pcsk9 Inhibitors ◽  
Cholesterol Levels ◽  
Lowering Therapy

Hypercholesterolemia (CH) is defined as the elevation of serum cholesterol levels, especially low-density lipoprotein (LDL) cholesterol, which is considered to be one of the most relevant risk factors for triggering cardiovascular disease, for This is vitally important to start treatment, there are several highly useful pharmacological groups for lipid-lowering therapy, among them we highlight the PCSK9 inhibitors, among the molecules that are part of this group we find inclisirán, this being a structure that promises a lot in regarding the management of hypercholesterolemia.

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