Combined lipid-lowering therapy from standpoint of modern guidelines for management of dyslipidaemias

2021 ◽  
pp. 13-19
Author(s):  
O. D. Ostroumova ◽  
A. I. Kochetkov ◽  
A. I. Listratov
Keyword(s):  
Statin Therapy ◽  
Safety Profile ◽  
High Intensity ◽  
Residual Risk ◽  
Lipid Lowering ◽  
High Density Lipoproteins ◽  
Lipid Lowering Therapy ◽  
Lowering Therapy ◽  
Increased Risk ◽  
Wide Range

Coronary artery disease (CAD) remains the leading cause of death, and its prevalence is projected to increase in the near future. Dyslipidemia is one of the most important risk factors for CAD, and special attention is currently being paid to improving approaches to its correction. In the new revision of the Russian Guidelines for the Management of Patients with dyslipidemia (2020), priorities are given to high-intensity statin therapy: new more strict target levels of low-density lipoprotein cholesterol (LDL–C) are introduced. Experts also emphasize the important role of the cholesterol fraction of non-high-density lipoproteins (non-HDL–C), primarily triglycerides, and introduce their target levels. The concept of residual risk, which remains despite effective statin therapy and achievement of the target level of LDL–C, is closely related to non-HDL–C. Here, hypertriglyceridemia is of crucial importance, contributing to an increased risk of coronary heart disease and cardiovascular mortality. Therefore, combined lipid-lowering therapy in the form of a combination of high-intensity statin and fenofibrate is an effective approach to significantly improve the prognosis and reduce the residual risk. According to research data, rosuvastatin provides a reduction in LDL–C by ≥ 50 %, has a wide range of pleiotropic effects in combination with an optimal safety profile. Fenofibrate allows you to effectively reduce the level of triglycerides and implements additional protective effects on the cardiovascular system. The logical continuation of the principle of combined lipid-lowering therapy was the appearance of a fixed combination (FC) of rosuvastatin and fenofibrate, which already has its own evidence base of studies indicating a complex and complementary effect on the disturbed blood lipid spectrum, a good safety profile of therapy, and the form of ‘single-pill’ significantly increases patients adherence to treatment. It can be expected that the widespread use of rosuvastatin and fenofibrate in clinical practice will effectively reduce the residual cardiovascular risk and thus provide an improved prognosis for patients.

scholarly journals PCSK9 inhibitors for in-hospital treatment of patients with acute coronary syndrome and severe lipid metabolism disorders

2020 ◽  
Vol 25 (8) ◽  
pp. 4010
Author(s):  
O. L. Barbarash ◽  
N. V. Fedorova ◽  
D. Yu. Sedykh ◽  
O. V. Gruzdeva ◽  
O. N. Khryachkova ◽  
...  
Keyword(s):  
Acute Coronary Syndrome ◽  
Statin Therapy ◽  
Lipid Lowering ◽  
High Density Lipoproteins ◽  
Hospital Treatment ◽  
Lipid Lowering Therapy ◽  
Pcsk9 Inhibitor ◽  
Coronary Syndrome ◽  
Lowering Therapy ◽  
Baseline Values

Aim. To assess the efficacy and safety of PCSK9 inhibitor alirocumab as part of a combination lipid-lowering therapy in patients with acute coronary syndrome (ACS).Material and methods. This prospective, open-label, single-center activetreatment study included 13 patients hospitalized due to ACS. The main inclusion criterion was nonachievement of target low-density lipoprotein cholesterol (LDL-C) values (<1,4 mmol/L) with high-intensity statin therapy prior to ACS. During the first 30 days after ACS, all patients received therapy with atorvastatin 40-80 mg/day or rosuvastatin 20-40 mg/day in combination with alirocumab 150 mg/ml (Praluent) administered by subcutaneous injection. Lipid and biochemical profiles were monitored. The first injection of the PCSK9 inhibitor was performed on days 3-5 of hospitalization, the second — after 2 weeks.Results. On admission, the median LDL-C was 4,3 [3,5;5,3] mmol/L. A day after administration, there was a decrease in LDL-C by 41,9% (median 2,5 [1,8;3,2] mmol/L; p=0,001) without a negative effect on high-density lipoproteins (HDL-C) (median 1,2 [0,8;1,4] mmol/L; p=0,270). Before the next injection, LDL-C decreased by another 8% (median 2,3 [1,1;4,1] mmol/L). A day after the second injection, a decrease in LDL-C from the baseline values was 69,8% (median 1,3 [0,7;1,5] mmol/L; p=0,010). Strengthening lipid-lowering therapy with a PCSK9 inhibitor within 30 days after ACS did not lead to clinical and biochemical deterioration.Conclusion. The use of subcutaneous 150-mg injections of alirocumab 2 times a week 30 days after ACS in patients who did not reach target LDL-C values with statin therapy, leads to a 69% decrease in LDL-C from baseline values and is safe.

scholarly journals Effectiveness of lipid-lowering therapy in outpatients with coronary artery disease living in a large industrial center of Eastern Siberia

2022 ◽  
Vol 20 (8) ◽  
pp. 3135
Author(s):  
N. G. Gogolashvili ◽  
R. A. Yaskevich
Keyword(s):  
Coronary Artery Disease ◽  
Coronary Artery ◽  
Statin Therapy ◽  
High Intensity ◽  
Lipid Lowering ◽  
Moderate Intensity ◽  
Lipid Lowering Therapy ◽  
Target Level ◽  
Lowering Therapy ◽  
Artery Disease

Aim. To study the prescription rate of lipid-lowering therapy and achieving the target low-density lipoprotein cholesterol (LDL-C) values in outpatients with coronary artery disease (CAD) living in Krasnoyarsk.Material and methods. The study included all patients with CAD hospitalized in the cardiology department of the clinic of the Research Institute of Medical Problems of the North (Krasnoyarsk) in 2018-2019. The analysis included data from 1671 patients (men, 770; women, 901). During hospitalization, an in-depth survey of patients was carried out on the subject of prescribing and taking lipid-lowering drugs. On admission, lipid profile was assessed in all patients.Results. At the time of admission, only 51,4% of patients received lipidlowering therapy. The majority received statin monotherapy (99,2%). Only 0,8% of patients received combination therapy (statin+ezetimibe). The most frequently prescribed statin in the study was atorvastatin — 74,6%. Rosuvastatin was received by 17,1% of patients. In most cases, the doses of atorvastatin and rosuvastatin corresponded to the moderate-intensity statin therapy regimen. The frequently prescribed dose of atorvastatin was 20 mg/day — 54,4%, rosuvastatin — 10 mg/day — 68,7%. The target level of LDL-C <1,8 mmol/L was reached by 16,3%, <1,5 mmol/L — by 9,0%, <1,4 mmol/L — only 6,5% of patients. Most often, the target LDL-C levels were achieved by patients receiving high-intensity statin (HIS) therapy. The target level of LDL-C <1,8 mmol/L was reached by 37,5%, <1,5 mmol/L — 23,9%, LDL cholesterol <1,4 mmol/L — 20,7% of patients, receiving HIS.Conclusion. In patients with CAD living in Krasnoyarsk, the most commonly prescribed statins were atorvastatin and rosuvastatin, but only 32% of patients received HIS. Combination lipid-lowering therapy has been used extremely rarely. Among the surveyed patients, the current target level of LDL-C for patients with CAD (<1,4 mmol/L) was achieved only in 6,5% of patients. In the group of patients receiving high-intensity statin therapy, this target level was achieved in 20,7% of patients, which indicates the need for strict adherence to current clinical guidelines.

Abstract 13787: Efficacy of Lowering Low-density Lipoprotein Cholesterol in Elderly Subjects: A Systematic Review and Meta-analysis of Randomized Controlled Trials

Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Baris Gencer ◽  
Nicholas A Marston ◽  
KyungAh Im ◽  
Peter S Sever ◽  
Anthony C Keech ◽  
...  
Keyword(s):  
Statin Therapy ◽  
Coronary Revascularization ◽  
The Elderly ◽  
Lipid Lowering ◽  
Elderly Subjects ◽  
Lipid Lowering Therapy ◽  
Vascular Events ◽  
Randomized Controlled ◽  
Lowering Therapy ◽  
Myocardial Infraction

Introduction: The clinical benefit from LDL-C lowering therapy in the elderly remains debated. Aim: To synthesize the efficacy of lowering LDL-C in patients aged ≥75 years in the light of most recently published data. Methods: Medline database was searched for the most recent evidence (2015-2020). The key inclusion criterion was a randomized controlled cardiovascular outcome trial testing an LDL-C lowering therapy with data available in patients aged ≥75 years at randomization. For efficacy, we meta-analyzed the risk ratio (RR) of major vascular events (a composite of cardiovascular (CV) death, myocardial infarction, stroke or coronary revascularization) per 1-mmol/L reduction in LDL-C. Results: Among 244,090 patients from 29 trials, 21,492 (8.8%) were elderly; 11,750 from statin trials, 6209 from ezetimibe trials, and 3533 from PCSK9 inhibitor trials. Median follow-up ranged from 2.2-6.0 years. LDL-C lowering therapy significantly reduced major vascular events (n=3519) in the elderly by 26% per 1-mmol/L LDL-C reduction (RR 0.74 [0.61-0.89], P=0.002), which was at least as good as the magnitude of effect seen in the non-elderly patients (RR 0.85 [0.78-0.92]; P interaction =0.24). Amongst the elderly, the RR was similar for statin (0.81 [0.70-0.94]) and non-statin therapy (0.67 [0.47-0.95]; P interaction =0.60). The benefit of LDL-C lowering in the elderly was observed for each component of the composite, including CV death (RR 0.85 [0.73-0.996], P=0.045), myocardial infraction (RR 0.80 [0.70-0.92], P=0.001), stroke (RR 0.71 [0.58-0.87], P=0.001) and coronary revascularization (RR 0.78 [0.63-0.96], P=0.017). Conclusion: In patients 75 years and older, lipid-lowering therapy is as effective in reducing CV events as it is in younger adults. These results should strengthen guideline recommendations for the use of lipid-lowering therapies, including non-statin therapy, in the elderly.

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 &lt;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.

P5015Efficacy of lipid lowering therapy beyond statins to prevent cardiovascular events: A meta-analysis

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
I Dykun ◽  
R Mincu ◽  
M Totzeck ◽  
T Rassaf ◽  
A A Mahabadi
Keyword(s):  
Myocardial Infarction ◽  
Relative Risk ◽  
Statin Therapy ◽  
Risk Reduction ◽  
Cardiovascular Events ◽  
Ldl Cholesterol ◽  
Meta Analysis ◽  
Lipid Lowering ◽  
Lipid Lowering Therapy ◽  
Lowering Therapy

Abstract Background Lipid lowering therapy is a key cornerstone in secondary prevention of patients with coronary artery disease. However, only a minority of patients with statin therapy reach LDL thresholds as suggested by the ESC. Ezetimibe and proprotein convertase subtilisin/kexin type 9 (PCSK-9) inhibitors allow for reduction in LDL-cholesterol in addition to statin therapy. Purpose To perform a meta-analysis of existing trials, evaluating how lipid lowering therapy beyond statins impacts cardiovascular outcome. Methods We performed a systematic search using the Pubmed, Cochrane, SCOPUS, and Web of Science databases for studies, evaluating the impact of an intensified lipid lowering therapy via ezetimibe or PCSK-9 inhibitor in addition to statin therapy compared to statin therapy alone. Manuscript and congress presentations, published until 1st of November 2018, were included. We made our search specific and sensitive using Medical Subject Headings terms and free text and considered studies published in English language. Search terms used were “ezetimibe”, “evolocumab”, “alirocumab”, or “bococizumab” and “cardiovascular events”. Results A total of 100,610 patients from 9 randomized controlled trials (IMPROVE-IT, FOURIER, ODYSSEY Outcomes, SIPRE I, SPIRE II, ODYSSEY LONG TERM, OSLER-1 and OSLER-2, HIJ-PROPER) were included. Treatment with ezetimibe or a PCSK-9 inhibitor was associated with a 18% risk reduction in cardiovascular events (OR [95% CI]: 0.82 [0.75–0.89]). Effect sizes were similar for myocardial infarction (0.84 [0.76–0.92]) and even more pronounced for ischemic stroke (0.77 [0.67–0.83]). In contrast, all-cause mortality was not improved by the intensified lipid lowering therapy (0.94 [0.85–1.05]). No relevant heterogeneity and inconsistency between groups was present in all analyses (detailed data not shown). Comparing efficacy of LDL-reduction and relative risk redaction of cardiovascular events, a linear relationship was observed (figure). Figure 1. Correlation of reduction of LDL-cholesterol at one year with relative risk reduction (95% confidence interval) of cardiovascular events in included trials. Conclusion Intensified LDL-lowering therapy with ezetimibe or PCSK-9 inhibitors, in addition to statins, reduces the risk of myocardial infarction and stroke, however, does not impact overall mortality. There is a linear relationship between LDL reduction and cardiovascular risk reduction, confirming the beneficial effects of LDL lowering therapy beyond statins in secondary prevention.

Effects of lipid-lowering therapy on major adverse limb events in patients with peripheral arterial disease: A meta-analysis of randomized clinical trials

Vascular ◽  
2021 ◽  
pp. 170853812110439
Author(s):  
Walter Masson ◽  
Martín Lobo ◽  
Leandro Barbagelata ◽  
Graciela Molinero ◽  
Ignacio Bluro
Keyword(s):  
Clinical Trials ◽  
Randomized Clinical Trials ◽  
Meta Analysis ◽  
Arterial Disease ◽  
Lipid Lowering ◽  
Placebo Control ◽  
Lipid Lowering Therapy ◽  
Lowering Therapy ◽  
Increased Risk ◽  
Peripheral Arterial

Objective Patients with peripheral artery disease (PAD) are at increased risk of major adverse limb events (MALE). Furthermore, MALE have several clinical implications and a poor prognosis, so prevention is a fundamental issue. The main objective of the present meta-analysis of randomized clinical trials is to evaluate the effect of different lipid-lowering therapies on MALE incidence in patients with PAD. Methods A meta-analysis of randomized studies that evaluated the use of lipid-lowering therapy in patients with PAD and reported MALE was performed, after searching the PubMed/MEDLINE, Embase, ScieLO, Google Scholar, and Cochrane Controlled Trials databases. A fixed- or random-effects model was used. Results Five randomized clinical trials including 11,603 patients were identified and considered eligible for the analyses (5903 subjects were allocated to receive lipid-lowering therapy, while 5700 subjects were allocated to the respective placebo/control arms). The present meta-analysis revealed that lipid-lowering therapy was associated with a lower incidence of MALE (OR: 0.76, 95% confidence interval: 0.66–0.87; I2: 28%) compared to placebo/control groups. The sensitivity analysis shows that the results are robust. Conclusion This study demonstrated that the use of lipid-lowering therapy compared with the placebo/control arms was associated with a marked reduction in the risk of MALE. Physicians involved in the monitoring and treatment of patients with PAD must work hard to ensure adequate lipid-lowering medication in these patients.

scholarly journals Use of Lipid-lowering Agents in Rheumatoid Arthritis: A Population-based Cohort Study

2013 ◽  
Vol 40 (7) ◽  
pp. 1082-1088 ◽  
Author(s):  
Bharath Manu Akkara Veetil ◽  
Elena Myasoedova ◽  
Eric L. Matteson ◽  
Sherine E. Gabriel ◽  
Cynthia S. Crowson
Keyword(s):  
Rheumatoid Arthritis ◽  
General Population ◽  
Population Based ◽  
Lipid Lowering ◽  
Lipid Lowering Therapy ◽  
Lowering Therapy ◽  
Kaplan Meier ◽  
Increased Risk ◽  
Lipid Testing ◽  
Lipid Lowering Agents

Objective.Rheumatoid arthritis (RA) is associated with an increased risk of cardiovascular disease and mortality. Lipid-lowering therapy is reportedly underused in patients with RA. Longitudinal cohort studies comparing use of lipid-lowering medications in patients with RA versus the general population are lacking.Methods.Cardiovascular risk factors, lipid measures, and use of lipid-lowering agents were assessed in a population-based inception cohort of patients with RA and a cohort of non-RA subjects followed from January 1, 1988, to December 31, 2008. The National Cholesterol Education Program (NCEP) Adult Treatment Panel III (ATPIII) guidelines were assessed at the time of each lipid measure throughout followup. Time from meeting guidelines to initiation of lipid-lowering agents was assessed using Kaplan-Meier methods.Results.The study population included 412 RA and 438 non-RA patients with ≥ 1 lipid measure during followup and no prior use of lipid-lowering agents. Rates of lipid testing were lower among patients with RA compared to non-RA subjects. Among patients who met NCEP ATPIII criteria for lipid-lowering therapy (n = 106 RA; n = 120 non-RA), only 27% of RA and 26% of non-RA subjects initiated lipid-lowering agents within 2 years of meeting the guidelines for initiation.Conclusion.There was substantial undertreatment in both the RA and the non-RA cohorts who met NCEP ATPIII criteria for initiation of lipid-lowering agents. Patients with RA did not have as frequent lipid testing as individuals in the general population.

Proprotein convertase subtilisin/kexin type 9 in kidney disease

2019 ◽  
Vol 34 (8) ◽  
pp. 1266-1271 ◽  
Author(s):  
David Schmit ◽  
Danilo Fliser ◽  
Thimoteus Speer
Keyword(s):  
Kidney Disease ◽  
Statin Therapy ◽  
Kidney Function ◽  
Plasma Levels ◽  
Vascular Lesions ◽  
Lipid Lowering ◽  
Lipid Lowering Therapy ◽  
Proprotein Convertase ◽  
Pcsk9 Inhibitors ◽  
Increased Risk

Abstract Chronic kidney disease (CKD) is associated with a substantially increased risk for the development of atherosclerotic cardiovascular (CV) disease. Accordingly, CV mortality is increased even in the earliest stages of CKD. In the general population and in CKD patients, high plasma levels of low-density lipoprotein cholesterol (LDL-C) are crucially involved in the initiation and progression of atherosclerotic vascular lesions. Lowering LDL-C by use of statins and/or ezetimibe represents the gold standard of lipid-lowering therapy, with a great body of evidence from several large clinical trials. Statin therapy reduces CV events in patients with normal and impaired kidney function alike, while the evidence for patients on maintenance haemodialysis is weaker. The inhibition of proprotein convertase subtilisin/kexin type 9 (PCSK9) serine protease represents a novel lipid-lowering tool. Currently the monoclonal antibodies evolocumab and alirocumab are the approved PCSK9 inhibitors. Despite maximum-tolerated statin therapy, they efficiently further reduce LDL-C plasma levels without any major adverse effects. Moreover, in large clinical outcome trials, both antibodies have been proven to lower CV events. Notably, the LDL-lowering capacity was independent of baseline kidney function and also efficient in patients with moderate CKD. However, patients with severely impaired kidney function, that is, the population at the highest CV risk, have been excluded from those trials. The relevance of the LDL-independent effects of PCSK9 inhibitors, such as lowering lipoprotein(a) or ameliorating dyslipidaemia in patients with nephrotic syndrome, has to be determined. Therefore further specific studies assessing the effects and outcomes of PCSK9-inhibiting treatment in CKD patients are warranted.

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