The most influential ILEP papers
Title of the ILEP paper
Year of the publication
Impact on recommendations and clinical practice
1. Statin intolerance -an attempt at a unified definition. Position paper from an International Lipid Expert Panel.
2015
One of the first statin intolerance definition, which for the first time gave clear practicalre commendations on the management with the risk factors and conditions (e.g.: intensiveexertion, alcohol consumption, major surgery, chronic renal and liver disease) disease, that may increase the risk of statin associated side effects.
2. Lipid lowering nutraceuticals in clinical practice: position paper from an International Lipid Expert Panel.
2017
The ILEP was the first that prepared the recommendations on the potential applications of natural products (nutraceuticals) in different conditions, including lipid disorders, with very detailed guidance not only on the efficacy based on available EBM, but foremost on safety on nutraceuticals. In fact, since the time of these recommendations, the discussion around nutrivigilance started.
3. The Role of Nutraceuticals in Statin Intolerant Patients.
2018
The ILEP was the first that prepared the recommendations on possible applications of natural products (nutraceuticals) in a very challengeable group of patients with statin intolerance. These recommendations clearly showed that there are only few to several nutraceuticals that have enough EBM to support treatment (mostly in low to moderate CVD risk patients) in subjects with confirmed statin intolerance (both partial and complete).
4. Introducing the 'Drucebo' effect in statin therapy: a systematic review of studies comparing reported rates of statin-associated muscle symptoms, under blinded and open-label conditions.
2018
In 2018 the ILEP introduced the term of the drucebo effect that should be used, instead of the nocebo effect, for the statin therapy describing the phenomenon of the statin associated side effects that are not attributable to the therapy buy to the psychological attitude. The concept of 'drucebo' effect (a combination of DRUg and plaCEBO or noCEBO) relates to beneficial or adverse effects of a drug, which result from expectation and are not pharmacologically caused by the drug. As a result of the systematic review, we also confirmed that the contribution of the drucebo effect to statin-associated muscle may range between 38% and 78%, which was next confirmed in well-recognized n-of-1 trials.
5. Lower carbohydrate diets and all-cause and cause-specific mortality: a population-based cohort study and pooling of prospective studies.
2019
Extensive ILEP and LBPMC Group NHANES study analysis and meta-analysis (9 studies with >460 thousand patients). It showed unfavourable association of a low carbohydrate diet with overall and cause-specific mortality, especially in those without indications and with longer application (over 2 years) based on both new analyses of an established cohort and by pooling available cohort studies.
6. LDL-C: lower is better for longer-even at low risk.
2020
The ILEP, to the best knowledge, was the first that made an attempt of recommendations how to manage lipid disorders in low to moderate risk patients, what is the role of lifestyle changes (diet and regular exercise) and when and how effectively to start with lipid lowering therapy in this group of patients according to the rule “the earlier, the better”.
7. Statin therapy in athletes and patients performing regular intense exercise-Position paper from the International Lipid Expert Panel (ILEP)
2020
These ILEP guidelines were the first to present the important issue of statin and lipid lowering therapy in athletes/people with regular individually intensive exertion, in the form of step-by-step practical recommendations. It is of special importance as we might observe more and more individuals on regular exercises/athletes requiring statin therapy due to their cardiovascular risk.
8. Efficacy and safety of bempedoic acid for the treatment of hypercholesterolemia: A systematic review and meta-analysis.
2020
It was one of the first and most extensive meta-analysis on new lipid lowering intervention (then) with bempedoic acid based on the data from phase 2 and phase 3 RCTs that clearly showed not only its effectiveness on, among others, LDL-C cholesterol, non-HDL cholesterol and apolipoprotein B, but also significant effect on C-reactive protein (that was next confirmed in the CLEAR Outcomes study) and large safety, including even 41% less risk of new onset diabetes, what is still a matter of investigation. Based on this data, the first Polish Lipid Association recommendations on the bempedoic acid indications were published in Sept. 2021.
9. Brief recommendations on the management of adult patients with familial hypercholesterolemia during the COVID-19 pandemic
2020
At the beginning of the pandemic there was a large fear not only on whether it will be possible to diagnose and treat FH patients in hospitals and ambulatory clinics (due to lockdown and other restrictions), but whether the drugs used for Covid-19 patients can give drug-to-drug interactions with statins and other lipid-lowering therapies. At the beginning of the pandemic, the ILEP together with the FH-Europe prepared the guidance on how to effectively treat FH patients.
10. Optimal use of lipid-lowering therapy after acute coronary syndromes: A Position Paper endorsed by the International Lipid Expert Panel (ILEP).
2021
In April 2021 one of the most important ILEP recommendations were published, that were the answer on the high ineffectivenesson LDL-C goal attainment in very high risk patients. These Position Paper not only extended the definition of the extremely highCVD risk patients that was introduced in 2019 year in the ESC/EAS guidelines, but foremost recommended upfront combination lipid lowering therapy in very high risk and extremely high risk patients after ACS and FH. They were next approved in many national guidelines, as well as in ESC guidelines on ACS management (2023).
11. The impact of type of dietary protein, animal versus vegetable, in modifying cardiometabolic risk factors: A position paper from the International Lipid Expert Panel (ILEP).
2021
The aim of this expert opinion ILEP recommendation (the first such comprehensive on this issue) was to elucidate the different impact of animal vs vegetable protein on modifying cardiometabolic risk factors. Many observational and interventional studies confirmed that increasing plant-based proteins and certain animal-based proteins have a positive effect in modifying cardiometabolic risk factors. But it is recommended to substitute red meat with poultry or fish in order to lower CVD risk. Specific amino acids have favourable results in modifying major risk factors for CVD, such as hypertension. Apart from meat, other animal-source proteins, like those found in dairy products are inversely correlated to hypertension, obesity and insulin resistance.
12. Impact of nutraceuticals on markers of systemic inflammation: Potential relevance to cardiovascular diseases-A position paper from the International Lipid Expert Panel (ILEP).
2021
Inflammation is a critical residual CVD risk factor. The main problem, however, is that we even measure CRP, we do not know how to manage elevated CRP/hsCRP levels. Thus, waiting for the new effective drugs (besides unused colchicine) –such as ziltivekimab, we might try to reduce hsCRP with lifestyle changes, including exercise, and dedicated diet, enhanced with naturalproducts that have anti-inflammatory properties. This ILEP recommendations was the first to prompt which dietary components might help to reduce inflammatory biomarkers, and in the consequence residual CVD risk.
13. Association of statin use in older people primary prevention group with risk of cardiovascular events and mortality: a systematic review and meta-analysis of observational studies.
2021
Inflammation is a critical residual CVD risk factor. The main problem, however, is that we even measure CRP, we do not know how to manage elevated CRP/hsCRP levels. Thus, waiting for the new effective drugs (besides unused colchicine) –such as ziltivekimab, we might try to reduce hsCRP with lifestyle changes, including exercise, and dedicated diet, enhanced with naturalproducts that have anti-inflammatory properties. This ILEP recommendations was the first to prompt which dietary components might help to reduce inflammatory biomarkers, and in the consequence residual CVD risk.
14. Prevalence of statin intolerance: a meta-analysis.
2022
In this largest ever meta-analysis on statin intolerance patients that combined 176 studies with almost 4.2 million subjects, weshowed that real SI prevalence is low, only 9.1%, and even lower between 5.9-7% while diagnosed with established definitions (including the ILEP2015 one). There are also well-recognized risk factors of SI, including nonmodifiable, like age and gender (11/100 women and 7/100 man may suffer SAMS), obesity, diabetes, liver and kidney disease, thyroid disease, some drugs. On the other hand, the analysis also clearly showed that SI is mostly overdiagnosed, with critical role of the drucebo effect, and as many as 95% of patients might use statin therapy without any safety concerns.
15. Step-by-step diagnosis and management of the nocebo/drucebo effect in statin-associated muscle symptoms patients: a position paper from the International Lipid Expert Panel (ILEP).
2022
The first recommendations focused on how to overcome the nocebo/drucebo effect that might be responsible for at least 70% of allstatin-associated side effects. The recommendations introduced few practical and easy to follow algorithms, starting from the personal lipid intervention plan (PLIP) one, which emphasize the role of education and good communication with patients on the disease, CVD risk, lifestyle changes, therapies and side effects. Two others (MEDS and SLAP) help to optimally manage with SI patients. The recommendations presented also detailed indications on how to proceed with the patients with elevated liver enzymes, creatine kinase, and those at the risk of NOD.
16. Personalized management of dyslipidemias in patients with diabetes-it is time for a new approach (2022)
2022
Nowadays, the access to lipid lowering therapies allows for not only effective LDL-C reduction, but also to reduce the risk of any side effects, and to improve other parameters related to coexistent risk factors or diseases within therapy personalization. Such an approach the ILEP proposed for patients with metabolic disorders (obesity, prediabetes, metabolic syndrome, diabetes), suggesting that effective lipid lowering therapy and improvement of the cardiometabolic parameters might be achieved with the application of e.g. pitavastatin, combination therapy, non-statin drugs like bempedoic acid or PCSK9 targeted therapy approach. Also, perspective drugs, like new CETP inhibitor –obicetrapib hold promise for not only effective LDL-C reduction, but also reduction of the risk o NODM.
17. The association between daily step count and all-cause and cardiovascular mortality: a meta-analysis.
2023
One of the largest meta-analyses on the role of steps on cardiovascular and all-cause mortality. 17 cohort studies with almost 227,000 generally healthy participants were included (median follow-up 7.1 years). We noticed that starting from about 4000 steps CVD and all-cause mortality significant benefits were observed. Each 1000-step increment was associated with a 15% decreased risk of all-cause mortality, while a 500-step increment was associated with a 7% decrease in CV mortality. A dose-response association between step count andall-cause and CV mortality was observed with a progressively lower risk of mortality with an increased step count with the optimal number of 6-10,000 steps/day for 60+ subjects and 7-13,000 for younger ones.
18. Bempedoic acid in the management of lipid disorders and cardiovascular risk. 2023 position paper of the International Lipid Expert Panel (ILEP)
2023
The first recommendations on the role and place of the bempedoic acid published simultaneously with the CLEAR Outcomes study release at the ACC Congress in the New Orleans. Practical evidence-based guidance (following the previous ILEP approach of the upfront combination LLT) is provided relating to the use of bempedoic acid in atherosclerotic CVD, familial hypercholesterolaemia, and statin intolerance. The authors also attempted to recommend its role in the therapy of patients in primary prevention, those with elevated hsCRP and at the risk of NODM.
19. 2024 Recommendations on the Optimal Use of Lipid-Lowering Therapy in Established Atherosclerotic Cardiovascular Disease and Following Acute Coronary Syndromes: A Position Paper of the International Lipid Expert Panel (ILEP)
2024
The update of the 2021 ILEP recommendations on the upfront lipid lowering combination therapy. The authors decided not only to add new existing therapies to the recommendations suggesting even quadruple combination therapy in extremely high risk patients and those with FH, but also strongly recommended upfront combination LLT already in patients with established ASCVD pre-event. Additionally, based on the RWE data, and approving the previous 2022 ILEP recommendations on patients with metabolic disorders, they suggested personalizedapproach for patients with/at the risk of diabetes, and in statin intolerant patients, emphasizing the role of upfront lipid lowering combination therapy of moderate intensity statin therapy plus ezetimibe (if HIS cannot be applied) that (in comparison to statin in monotherapy) can significantly more effectively reduce LDL-C, increase the number of patients on LDL-C goal, reduce the risk of SEs and discontinuation and the risk of CVOT and mortality.
20. Management of children with heterozygous familial hypercholesterolemia worldwide: a meta-analysis
2025
The largest meta-analysis on the prevalence, diagnosis and treatment of heFH children. 41 studies with 4667 paediatric patients at mean age 12 years were included. The most significant reduction of LDL-C was observed for the combination therapy of statins and ezetimibe, statin therapy and PCSK9 inhibitors. The pooled LDL-C was reduced by 33.44% and a total of only 38.7% of children achieved the LDL-C goal. The analysis confirmed that all parameters related to endocrine function and demographic indices were unaffected by LLT therapy, andthe AEs were not reported significantly higher when compared to the control; the prevalence of therapy discontinuation was only 0.8%.
The most cited ILEP papers
Title of the ILEP paper
Reference
Number of citations in WoS
Number of citations in SCOPUS
Number of citations in Google Scholar
Altmetric Score
Top cited by the WoS
1. Lipid lowering nutraceuticals in clinical practice: position paper from an International Lipid Expert Panel.
Cicero AFG, Colletti A, Bajraktari G, et al. Arch Med Sci. 2017 Aug;13(5):965-1005. doi: 10.5114/aoms.2017.69326.
Cicero AFG, Colletti A, Bajraktari G, et al. Nutr Rev. 2017 Sep 1;75(9):731-767. doi: 10.1093/nutrit/nux047.
660
463
561
47
YES
2. Statin intolerance -an attempt at a unified definition. Position paper from an International Lipid Expert Panel.
Banach M, Rizzo M, Toth PP, et al. Arch Med Sci. 2015 Mar 16;11(1):1-23. doi: 10.5114/aoms.2015.49807.
Banach M, Rizzo M, Toth PP, et al. Expert Opin Drug Saf. 2015 Jun;14(6):935-55. doi: 10.1517/14740338.2015.1039980.
363
451
600
23
YES
3. Prevalence of statin intolerance: a meta-analysis.
Bytyçi I, Penson PE, Mikhailidis DP, et al. Eur Heart J. 2022 Sep 7;43(34):3213-3223. doi: 10.1093/eurheartj/ehac015.
262
277
378
1260
YES
4. The Role of Nutraceuticals in Statin Intolerant Patients.
Banach M, Patti AM, Giglio RV, et al. J Am Coll Cardiol. 2018 Jul 3;72(1):96-118. doi: 10.1016/j.jacc.2018.04.040.
202
217
286
56
NO
5. Lower carbohydrate diets and all-cause and cause-specific mortality: a population-based cohort study and pooling of prospective studies.
Mazidi M, Katsiki N, Mikhailidis DP, Sattar N, Banach M. Eur Heart J. 2019 Sep 7;40(34):2870-2879. doi: 10.1093/eurheartj/ehz174.
97
114
131
276
NO
6. Safety of red yeast rice supplementation: A systematic review and meta-analysis of randomized controlled trials.
Fogacci F, Banach M, Mikhailidis DP, et al. Pharmacol Res. 2019 May;143:1-16. doi: 10.1016/j.phrs.2019.02.028.
97
105
119
42
NO
7. The impact of type of dietary protein, animal versus vegetable, in modifying cardiometabolic risk factors: A position paper from the International Lipid Expert Panel (ILEP).
Zhubi-Bakija F, Bajraktari G, Bytyçi I, et al. Clin Nutr. 2021 Jan;40(1):255-276. doi: 10.1016/j.clnu.2020.05.017.
85
97
128
55
NO
8. Optimal use of lipid-lowering therapy after acute coronary syndromes: A Position Paper endorsed by the International Lipid Expert Panel (ILEP).
Banach M, Penson PE, Vrablik M, et al. Pharmacol Res. 2021 Apr;166:105499. doi: 10.1016/j.phrs.2021.105499.
84
88
80
30
NO
9. The association between daily step count and all-cause and cardiovascular mortality: a meta-analysis.
Banach M, Lewek J, Surma S, et al. Eur J Prev Cardiol. 2023 Dec 21;30(18):1975-1985. doi: 10.1093/eurjpc/zwad229.
83
88
153
6327
NO
10. Introducing the 'Drucebo' effect in statin therapy: a systematic review of studies comparing reported rates of statin-associated muscle symptoms, under blinded and open-label conditions.
Penson PE, Mancini GBJ, Toth PP, et al. J Cachexia Sarcopenia Muscle. 2018 Dec;9(6):1023-1033. doi: 10.1002/jcsm.12344.
82
86
107
33
NO
11. LDL-C: lower is better for longer-even at low risk.
Penson PE, Pirro M, Banach M. BMC Med. 2020 Oct 8;18(1):320. doi: 10.1186/s12916-020-01792-7.
80
84
134
42
NO
12. Efficacy and safety of bempedoic acid for the treatment of hypercholesterolemia: A systematic review and meta-analysis.
Cicero AFG, Fogacci F, Hernandez AV, Banach M. PLoS Med. 2020 Jul 16;17(7):e1003121. doi: 10.1371/journal.pmed.1003121.
80
83
77
22
NO
13. Why patients with familial hypercholesterolemia are at high cardiovascular risk? Beyond LDL-C levels.
Bianconi V, Banach M, Pirro M. Trends Cardiovasc Med. 2021 May;31(4):205-215. doi: 10.1016/j.tcm.2020.03.004.
59
55
93
22
NO
14. Association of types of dietary fats and all-cause and cause-specific mortality: A prospective cohort study and meta-analysis of prospective studies with 1,164,029 participants.
Mazidi M, Mikhailidis DP, Sattar N, et al. Clin Nutr. 2020 Dec;39(12):3677-3686. doi: 10.1016/j.clnu.2020.03.028.
56
64
76
53
NO
15. Step-by-step diagnosis and management of the nocebo/drucebo effect in statin-associated muscle symptoms patients: a position paper from the International Lipid Expert Panel (ILEP).
Penson PE, Bruckert E, Marais D, et al. J Cachexia Sarcopenia Muscle. 2022 Jun;13(3):1596-1622. doi: 10.1002/jcsm.12960.
54
58
61
208
NO
