Atherosclerotic cardiovascular disease (ASCVD) and consequent acute coronary syndromes (ACS) are substantial contributors to morbidity and mortality across Europe. Fortunately, as much as two thirds of this disease's burden is modifiable, in particular by lipid-lowering therapy (LLT). Current guidelines are based on the sound premise that, with respect to low-density lipoprotein cholesterol (LDL-C), "lower is better for longer", and recent data have strongly emphasised the need for also "the earlier the better". In addition to statins, which have been available for several decades, ezetimibe, bempedoic acid (also as fixed dose combinations), and modulators of proprotein convertase subtilisin/kexin type 9 (PCSK9 inhibitors and inclisiran) are additionally very effective approaches to LLT, especially for those at very high and extremely high cardiovascular risk. In real life, however, clinical practice goals are still not met in a substantial proportion of patients (even in 70%). However, with the options we have available, we should render lipid disorders a rare disease. In April 2021, the International Lipid Expert Panel (ILEP) published its first position paper on the optimal use of LLT in post-ACS patients, which complemented the existing guidelines on the management of lipids in patients following ACS, which defined a group of "extremely high-risk" individuals and outlined scenarios where upfront combination therapy should be considered to improve access and adherence to LLT and, consequently, the therapy's effectiveness. These updated recommendations build on the previous work, considering developments in the evidential underpinning of combination LLT, ongoing education on the role of lipid disorder therapy, and changes in the availability of lipid-lowering drugs. Our aim is to provide a guide to address this unmet clinical need, to provide clear practical advice, whilst acknowledging the need for patient-centred care, and accounting for often large differences in the availability of LLTs between countries.

1st Department of Cardiology National and Kapodistrian University of Athens Athens Greece

2nd Department of Cardiology Faculty of Medicine Pavol Jozef Safarik University and East Slovak Institute of Cardiovascular Diseases Kosice Slovakia

3rd Department of Cardiology School of Medical Sciences in Zabrze Medical University of Silesia Katowice Poland

3rd Department of Medicine Department of Endocrinology and Metabolism of the 1st Faculty of Medicine Charles University and General University Hospital Prague Czech Republic

Centre of Cardiology North Estonia Medical Centre Tallinn University of Technology Tallinn Estonia

Clinic for Heart Blood Vessels and Rheumatic Diseases Medical Faculty Sarajevo University Clinical Center Sarajevo Sarajevo Bosnia and Herzegovina

Clinic of Cardiology University Clinical Centre of Kosova Medical Faculty University of Prishtina Prishtina Kosovo

Clinic of Cardiovascular Diseases University Hospital Center Zagreb School of Medicine University of Zagreb Zagreb Croatia

Department of Cardiology 2nd Faculty of Medicine Charles University and Motol University Hospital Prague Czech Republic

Department of Cardiology and Adult Congenital Heart Diseases Polish Mother's Memorial Hospital Research Institute Lodz Poland

Department of Cardiology and Cardiovascular Surgery University and Emergency Hospital Bucharest Romania

Department of Cardiology Center for Translational and Experimental Cardiology University Hospital Zurich Zurich Switzerland

Department of Cardiology South Buda Center Hospital St Imre University Teaching Hospital and Vascular and Heart Center of Semmelweis University Budapest Hungary

Department of Cardiology University Hospital Centre Sestre Milosrdnice Zagreb Croatia

Department of Cardiology University Hospital Institute of Medical Sciences University of Opole Opole Poland

Department of Cardiology University Medical Centre Ljubljana Ljubljana Slovenia

Department of Cardiology University of Medicine and Pharmacy Victor Babes Institute of Cardiovascular Diseases Research Center IBCVTIM Timisoara Romania

Department of Diabetes Nutrition and Metabolic Diseases Carol Davila University of Medicine and Pharmacy Bucharest Romania

Department of Family Medicine and Public Health University of Opole Opole Poland

Department of General Cardiology Middle Slovak Institute of Cardiovascular Diseases Banska Bystrica Slovakia

Department of General Medicine Emergency University Hospital St Anna Medical University of Sofia Sofia Bulgaria

Department of Gerontology and Geriatric PJ Safarik University Kosice Slovakia

Department of Internal Medicine and Clinical Pharmacology Medical University of Silesia Katowice Poland

Department of Internal Medicine and Geriatric Cardiology Medical Centre for Postgraduate Education Warsaw Poland

Department of Internal Medicine School of Medicine University of Banja Luka Banja Luka Republic of Srpska

Department of Internal Medicine School of Medicine University of Zagreb Zagreb Croatia

Department of Medicine Academy of Science and Arts Republic of Srpska Bosnia and Herzegovina Banja Luka Republic of Srpska

Department of Nutritional Sciences and Dietetics International Hellenic University Thessaloniki Greece

Department of Preventive Cardiology and Lipidology Medical University of Lodz Rzgowska 281 289 93 338 Lodz Poland

Division of Cardiology Department of Medicine Ciccarone Center for the Prevention of Cardiovascular Disease Johns Hopkins University School of Medicine Baltimore MD USA

Division of Medicine Department of Vascular Medicine Centre for Preventive Cardiology University Medical Centre Ljubljana Ljubljana Slovenia

Division of Metabolic Disease Department of Internal Medicine Faculty of Medicine University of Debrecen Debrecen Hungary

Division of Metabolic Diseases Department of Internal Medicine University Hospital Centre Zagreb Zagreb Croatia

Dyslipidaemia Department Institute of Cardiology AMS of Ukraine Kiev Ukraine

Faculty of Medicine and University Hospital Center for Endocrinology Diabetes and Preventive Medicine University of Cologne Cologne Germany

Faculty of Medicine Vilnius University Vilnius Lithuania

Institute of Cardiology and Regenerative Medicine University of Latvia and Pauls Stradins Clinical University Hospital Riga Latvia

Integrated Heart Center Shaare Zedek Medical Center Jerusalem Israel

Invasive Department Centre of Postgraduate Medical Education Warsaw Poland

Jagiellonian University Medical College Krakow Poland

Liverpool Centre for Cardiovascular Science Liverpool UK

Medical and Surgical Sciences Department Alma Mater Studiorum University of Bologna Bologna Italy

Medical Faculty University of Ljubljana Ljubljana Slovenia

MEDIPARK University Research Park PJ Safarik University Kosice Slovakia

School of Medicine European University Cyprus Nicosia Cyprus

School of Pharmacy and Biomolecular Sciences Liverpool John Moores University Liverpool UK

The 3rd Department of Internal Medicine Metabolic Care and Gerontology Charles University and University Hospital in Hradec Králové Hradec Králové Czech Republic

University of Medicine and Pharmacy Carol Davila University and Emergency Hospital Bucharest Romania

Vilnius University Hospital Santaros Klinikos Vilnius Lithuania

Zobrazit více v PubMed

Roth GA, et al. Global burden of cardiovascular diseases and risk factors, 1990–2019: update from the GBD 2019 study. J Am Coll Cardiol. 2020;76(25):2982–3021. PubMed PMC

Mensah GA, et al. Global burden of cardiovascular diseases and risks, 1990–2022. J Am Coll Cardiol. 2023;82(25):2350–473. PubMed PMC

Timmis A, et al. European Society of Cardiology: cardiovascular disease statistics 2019. Eur Heart J. 2020;41(1):12–85. PubMed

GBD 2021 Causes of Death Collaborators. Global burden of 288 causes of death and life expectancy decomposition in 204 countries and territories and 811 subnational locations, 1990–2021: a systematic analysis for the Global Burden of Disease Study 2021. Lancet. 2024; 403(10440):2100–2132. PubMed PMC

Barbato E, et al. Mapping interventional cardiology in Europe: the European Association of Percutaneous Cardiovascular Interventions (EAPCI) Atlas Project. Eur Heart J. 2020;41(27):2579–88. PubMed

Ference BA et al. Low-density lipoproteins cause atherosclerotic cardiovascular disease. 1. Evidence from genetic, epidemiologic, and clinical studies. A consensus statement from the European Atherosclerosis Society Consensus Panel. Eur Heart J. 2017;38(32):2459–2472. PubMed PMC

Banach M, Surma S. A look to the past—what has had the biggest impact on lipids in the last four decades? A personal perspective. Arch Med Sci. 2023;19(3):559–64. 10.5114/aoms/166256. PubMed PMC

Banach M, et al. Bempedoic acid in the management of lipid disorders and cardiovascular risk. 2023 position paper of the International Lipid Expert Panel (ILEP). Prog Cardiovasc Dis. 2023;79:2–11. PubMed

Ray KK, et al. Efficacy and safety of bempedoic acid among patients with and without diabetes: prespecified analysis of the CLEAR Outcomes randomised trial. Lancet Diabetes Endocrinol. 2024;12(1):19–28. PubMed

Henney NC, Banach M, Penson PE. RNA silencing in the management of dyslipidemias. Curr Atheroscler Rep. 2021;23(11):69. 10.1007/s11883-021-00968-7. PubMed PMC

Surma S, Shapiro MD, Banach M. Breaking new ground in lipid management: Insights from the 2024 American College of Cardiology Scientific Sessions. Pharmacol Res. 2024;205: 107246. PubMed

Robinson JG, et al. Enhancing the value of PCSK9 monoclonal antibodies by identifying patients most likely to benefit. A consensus statement from the National Lipid Association. J Clin Lipidol. 2019; 13(4):525–537. PubMed

Boren J, et al. Low-density lipoproteins cause atherosclerotic cardiovascular disease: pathophysiological, genetic, and therapeutic insights: a consensus statement from the European Atherosclerosis Society Consensus Panel. Eur Heart J. 2020;41(24):2313–30. PubMed PMC

Ning H, Perak AM, Siddique J, Wilkins JT, Lloyd-Jones DM, Allen NB. Association between life’s essential 8 cardiovascular health metrics with cardiovascular events in the cardiovascular disease lifetime risk pooling project. Circ Cardiovasc Qual Outcomes. 2024;19: e010568. 10.1161/CIRCOUTCOMES.123.010568. PubMed PMC

Serban MC, et al. Statin intolerance and risk of coronary heart events and all-cause mortality following myocardial infarction. J Am Coll Cardiol. 2017;69(11):1386–95. PubMed

Banach M, Penson PE. Adherence to statin therapy: it seems we know everything, yet we do nothing. Eur Heart J Open. 2022;2(6):oeac071. 10.1093/ehjopen/oeac071. PubMed PMC

Ray KK, Haq I, Bilitou A, Manu MC, Burden A, Aguiar C, Arca M, Connolly DL, Eriksson M, Ferrières J, Laufs U, Mostaza JM, Nanchen D, Rietzschel E, Strandberg T, Toplak H, Visseren FLJ, Catapano AL; SANTORINI Study Investigators. Treatment gaps in the implementation of LDL cholesterol control among high- and very high-risk patients in Europe between 2020 and 2021: the multinational observational SANTORINI study. Lancet Reg Health Eur. 2023; 29:100624. 10.1016/j.lanepe.2023.100624. PubMed PMC

Schubert J, et al. Low-density lipoprotein cholesterol reduction and statin intensity in myocardial infarction patients and major adverse outcomes: a Swedish nationwide cohort study. Eur Heart J. 2021;42(3):243–52. PubMed PMC

Lee SJ, Joo JH, Park S, Kim C, Choi DW, Hong SJ, Ahn CM, Kim JS, Kim BK, Ko YG, Choi D, Jang Y, Nam CM, Hong MK. Combination lipid-lowering therapy in patients undergoing percutaneous coronary intervention. J Am Coll Cardiol. 2023;82(5):401–10. 10.1016/j.jacc.2023.05.042. PubMed

Byrne RA, Rossello X, Coughlan JJ, Barbato E, Berry C, Chieffo A, Claeys MJ, Dan GA, Dweck MR, Galbraith M, Gilard M, Hinterbuchner L, Jankowska EA, Jüni P, Kimura T, Kunadian V, Leosdottir M, Lorusso R, Pedretti RFE, Rigopoulos AG, Rubini Gimenez M, Thiele H, Vranckx P, Wassmann S, Wenger NK, Ibanez B; ESC Scientific Document Group. 2023 ESC Guidelines for the management of acute coronary syndromes. Eur Heart J. 2023; 44(38):3720–3826.

Visseren FLJ, et al. 2021 ESC Guidelines on cardiovascular disease prevention in clinical practice. Eur Heart J. 2021;42(34):3227–337. PubMed

Mach F, et al. 2019 ESC/EAS Guidelines for the management of dyslipidaemias: lipid modification to reduce cardiovascular risk. Eur Heart J. 2020;41(1):111–88. PubMed

Dyrbus K, et al. Risk-factors associated with extremely high cardiovascular risk of mid- and long-term mortality following myocardial infarction: analysis of the Hyperlipidaemia Therapy in tERtiary Cardiological cEnTer (TERCET) registry. Atherosclerosis. 2021;333:16–23. PubMed

Banach M, et al. Optimal use of lipid-lowering therapy after acute coronary syndromes: a position paper endorsed by the International Lipid Expert Panel (ILEP). Pharmacol Res. 2021;166: 105499. PubMed

Ray KK, Reeskamp LF, Laufs U, Banach M, Mach F, Tokgözoğlu LS, Connolly DL, Gerrits AJ, Stroes ESG, Masana L, Kastelein JJP. Combination lipid-lowering therapy as first-line strategy in very high-risk patients. Eur Heart J. 2022;43(8):830–3. PubMed

Penson PE, et al. 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). J Cachexia Sarcopenia Muscle. 2022;13(3):1596–622. PubMed PMC

Paponja K, Pećin I, Reiner Ž, Banach M. Bempedoic acid: new evidence and recommendations on use. Curr Opin Lipidol. 2024;35(1):41–50. PubMed

Banach M, et al. Personalized management of dyslipidemias in patients with diabetes-it is time for a new approach. Cardiovasc Diabetol. 2022;21(1):263. PubMed PMC

Banach M, Surma S, Kapłon-Cieślicka A, Mitkowski P, Dzida G, Tomasik T, et al. Position paper of the Polish expert group on the use of pitavastatin in the treatment of lipid disorders in Poland endorsed by the Polish Lipid Association. Lekarz POZ. 2023;9(6):309–26. PubMed PMC

Sosnowska B, Stepinska J, Mitkowski P, Bielecka-Dabrowa A, Bobrowska B, Budzianowski J, Burchardt P, Chlebus K, Dobrowolski P, Gasior M, Jankowski P, Kubica J, Mickiewicz A, Mysliwiec M, Osadnik T, Prejbisz A, Rajtar-Salwa R, Wita K, Witkowski A, Gil R, Banach M. Recommendations of the Experts of the Polish Cardiac Society (PCS) and the Polish Lipid Association (PoLA) on the diagnosis and management of elevated lipoprotein(a) levels. Arch Med Sci. 2024;20(1):8–27. PubMed PMC

Lewek J, Niedziela J, Desperak P, Dyrbuś K, Osadnik T, Jankowski P, Witkowski A, Bielecka-Dąbrowa A, Dudek D, Gierlotka M, Gąsior M, Banach M. Intensive statin therapy versus upfront combination therapy of statin and ezetimibe in patients with acute coronary syndrome: a propensity score matching analysis based on the PL-ACS data. J Am Heart Assoc. 2023;12(18): e030414. PubMed PMC

Banach M, Reiner Z, Cicero AFG, Sabouret P, Viigimaa M, Sahebkar A, Postadzhiyan A, Gaita D, Pella D, Penson PE. 2022: the year in cardiovascular disease - the year of upfront lipid lowering combination therapy. Arch Med Sci. 2022;18(6):1429–34. PubMed PMC

Ray KK, et al. EU-wide cross-sectional observational study of lipid-modifying therapy use in secondary and primary care: the DA VINCI study. Eur J Prev Cardiol. 2021;28(11):1279–89. PubMed

Vrablik M, Seifert B, Parkhomenko A, Banach M, Jóźwiak JJ, Kiss RG, Gaita D, Rašlová K, Zachlederova M, Bray S, Ray KK. Lipid-lowering therapy use in primary and secondary care in Central and Eastern Europe: DA VINCI observational study. Atherosclerosis. 2021;334:66–75. PubMed

Lin I, et al. Patterns of statin use in a real-world population of patients at high cardiovascular risk. J Manag Care Spec Pharm. 2016;22(6):685–98. PubMed PMC

Nowowiejska-Wiewióra A, Wita K, Mędrala Z, Tomkiewicz-Pająk L, Bujak K, Mizia-Stec K, Brzychczy P, Gąsior M, Gąsior Z, Kulbat A, Kalarus Z, Wojakowski W, Trzeciak P, Witkowski A, Banach M, Legutko J. Dyslipidemia treatment and attainment of LDL-cholesterol treatment goals in patients participating in the Managed Care for Acute Myocardial Infarction Survivors program. Kardiol Pol. 2023;81(4):359–65. PubMed

Kim BK, Hong SJ, Lee YJ, Hong SJ, Yun KH, Hong BK, Heo JH, Rha SW, Cho YH, Lee SJ, Ahn CM, Kim JS, Ko YG, Choi D, Jang Y, Hong MK; RACING investigators. Long-term efficacy and safety of moderate-intensity statin with ezetimibe combination therapy versus high-intensity statin monotherapy in patients with atherosclerotic cardiovascular disease (RACING): a randomised, open-label, non-inferiority trial. Lancet. 2022;400(10349):380–390. PubMed

Lee YJ, Cho JY, You SC, Lee YH, Yun KH, Cho YH, Shin WY, Im SW, Kang WC, Park Y, Lee SY, Lee SJ, Hong SJ, Ahn CM, Kim BK, Ko YG, Choi D, Hong MK, Jang Y, Kim JS. Moderate-intensity statin with ezetimibe vs. high-intensity statin in patients with diabetes and atherosclerotic cardiovascular disease in the RACING trial. Eur Heart J. 2023;44(11):972–983. PubMed

Lee SH, Lee YJ, Heo JH, Hur SH, Choi HH, Kim KJ, Kim JH, Park KH, Lee JH, Choi YJ, Lee SJ, Hong SJ, Ahn CM, Kim BK, Ko YG, Choi D, Hong MK, Jang Y, Kim JS. Combination moderate-intensity statin and ezetimibe therapy for elderly patients with atherosclerosis. J Am Coll Cardiol. 2023;81(14):1339–49. PubMed

Lee SJ, Joo JH, Park S, Kim C, Choi DW, Lee YJ, Hong SJ, Ahn CM, Kim JS, Kim BK, Ko YG, Choi D, Jang Y, Nam CM, Hong MK. Combination therapy with moderate-intensity atorvastatin and ezetimibe versus high-intensity atorvastatin monotherapy in patients treated with percutaneous coronary intervention in practice: assessing RACING generalizability. Eur Heart J Cardiovasc Pharmacother. 2023. 10.1093/ehjcvp/pvad083. PubMed PMC

Banach M. The upfront lipid-lowering combination therapy of statins and ezetimibe vs statin monotherapy in the reduction of cardiovascular outcomes. A meta-analysis. Presentation at the ESC Congress 2024 in London, 30th Aug 2024. https://esc365.escardio.org/presentation/287273

Wald NJ, Law MR. A strategy to reduce cardiovascular disease by more than 80%. BMJ. 2003;326(7404):1419. PubMed PMC

Grundy SM, Stone NJ, Bailey AL, Beam C, Birtcher KK, Blumenthal RS, et al. 2018 AHA/ACC/AACVPR/AAPA/ABC/ACPM/ADA/AGS/APhA/ASPC/NLA/pcna guideline on the management of blood cholesterol: executive summary: a report of the American College of Cardiology/American Heart Association task force on clinical practice guidelines. J Am Coll Cardiol. 2019;73(24):3168–209. PubMed

Banach M, Burchardt P, Chlebus K, Dobrowolski P, Dudek D, Dyrbuś K, Gąsior M, Jankowski P, Jóźwiak J, Kłosiewicz-Latoszek L, Kowalska I, Małecki M, Prejbisz A, Rakowski M, Rysz J, Solnica B, Sitkiewicz D, Sygitowicz G, Sypniewska G, Tomasik T, Windak A, Zozulińska-Ziółkiewicz D, Cybulska B. PoLA/CFPiP/PCS/PSLD/PSD/PSH guidelines on diagnosis and therapy of lipid disorders in Poland 2021. Arch Med Sci. 2021;17(6):1447–547. PubMed PMC

Katzmann JL, et al. Non-statin lipid-lowering therapy over time in very-high-risk patients: effectiveness of fixed-dose statin/ezetimibe compared to separate pill combination on LDL-C. Clin Res Cardiol. 2022;111(3):243–52. PubMed PMC

Penson P, McGowan M, Banach M. Evaluating bempedoic acid for the treatment of hyperlipidaemia. Expert Opin Investig Drugs. 2017;26(2):251–9. PubMed

Nissen SE, Lincoff AM, Brennan D, Ray KK, Mason D, Kastelein JJP, Thompson PD, Libby P, Cho L, Plutzky J, Bays HE, Moriarty PM, Menon V, Grobbee DE, Louie MJ, Chen CF, Li N, Bloedon L, Robinson P, Horner M, Sasiela WJ, McCluskey J, Davey D, Fajardo-Campos P, Petrovic P, Fedacko J, Zmuda W, Lukyanov Y, Nicholls SJ; CLEAR Outcomes investigators. bempedoic acid and cardiovascular outcomes in statin-intolerant patients. N Engl J Med. 2023;388(15):1353–1364. PubMed

Cicero AFG, Fogacci F, Hernandez AV, Banach M; Lipid and Blood Pressure Meta-Analysis Collaboration (LBPMC) Group and the International Lipid Expert Panel (ILEP). Efficacy and safety of bempedoic acid for the treatment of hypercholesterolemia: a systematic review and meta-analysis. PLoS Med. 2020;17(7):e1003121.

Leiter LA, Banach M, Catapano AL, Duell PB, Gotto AM Jr, Laufs U, Mancini GBJ, Ray KK, Hanselman JC, Ye Z, Bays HE. Bempedoic acid in patients with type 2 diabetes mellitus, prediabetes, and normoglycaemia: a post hoc analysis of efficacy and glycaemic control using pooled data from phase 3 clinical trials. Diabetes Obes Metab. 2022;24(5):868–80. PubMed PMC

Nicholls SJ, Nelson AJ, Lincoff AM, Brennan D, Ray KK, Cho L, Menon V, Li N, Bloedon L, Nissen SE. Impact of bempedoic acid on total cardiovascular events: a prespecified analysis of the CLEAR outcomes randomized clinical trial. JAMA Cardiol. 2024;9(3):245–53. PubMed PMC

Stroes ESG, Bays HE, Banach M, Catapano AL, Duell PB, Laufs U, Mancini GBJ, Ray KK, Sasiela WJ, Zhang Y, Gotto AM Jr. Bempedoic acid lowers high-sensitivity C-reactive protein and low-density lipoprotein cholesterol: analysis of pooled data from four phase 3 clinical trials. Atherosclerosis. 2023;373:1–9. PubMed

Ridker PM, Lei L, Louie MJ, Haddad T, Nicholls SJ, Lincoff AM, Libby P, Nissen SE; CLEAR Outcomes Investigators. Inflammation and cholesterol as predictors of cardiovascular events among 13,970 contemporary high-risk patients with statin intolerance. Circulation. 2024;149(1):28–35. PubMed PMC

Nissen SE, Menon V, Nicholls SJ, Brennan D, Laffin L, Ridker P, Ray KK, Mason D, Kastelein JJP, Cho L, Libby P, Li N, Foody J, Louie MJ, Lincoff AM. Bempedoic acid for primary prevention of cardiovascular events in statin-intolerant patients. JAMA. 2023;330(2):131–40. PubMed PMC

Banach M, Surma S, Kapłon-Cieślicka A, Mitkowski P, Dzida G, Tomasik T, Mastalerz-Migas A. Position paper of the Polish Expert Group on the use of pitavastatin in the treatment of lipid disorders in Poland endorsed by the Polish Lipid Association. Arch Med Sci. 2023;20(1):28–42. PubMed PMC

Watts GF, Gidding SS, Hegele RA, Raal FJ, Sturm AC, Jones LK, Sarkies MN, Al-Rasadi K, Blom DJ, Daccord M, de Ferranti SD, Folco E, Libby P, Mata P, Nawawi HM, Ramaswami U, Ray KK, Stefanutti C, Yamashita S, Pang J, Thompson GR, Santos RD. International Atherosclerosis Society guidance for implementing best practice in the care of familial hypercholesterolaemia. Nat Rev Cardiol. 2023;20(12):845–69. PubMed

Sahebkar A, et al. A comprehensive review on the lipid and pleiotropic effects of pitavastatin. Prog Lipid Res. 2021;84: 101127. PubMed

Grinspoon SK, Fitch KV, Zanni MV, Fichtenbaum CJ, Umbleja T, Aberg JA, Overton ET, Malvestutto CD, Bloomfield GS, Currier JS, Martinez E, Roa JC, Diggs MR, Fulda ES, Paradis K, Wiviott SD, Foldyna B, Looby SE, Desvigne-Nickens P, Alston-Smith B, Leon-Cruz J, McCallum S, Hoffmann U, Lu MT, Ribaudo HJ, Douglas PS; REPRIEVE Investigators. Pitavastatin to prevent cardiovascular disease in HIV infection. N Engl J Med. 2023;389(8):687–699. PubMed PMC

Lu MT, Ribaudo H, Foldyna B, Zanni MV, Mayrhofer T, Karady J, Taron J, Fitch KV, McCallum S, Burdo TH, Paradis K, Hedgire SS, Meyersohn NM, DeFilippi C, Malvestutto CD, Sturniolo A, Diggs M, Siminski S, Bloomfield GS, Alston-Smith B, Desvigne-Nickens P, Overton ET, Currier JS, Aberg JA, Fichtenbaum CJ, Hoffmann U, Douglas PS, Grinspoon SK; REPRIEVE Trial Writing Group. Effects of pitavastatin on coronary artery disease and inflammatory biomarkers in HIV: mechanistic substudy of the REPRIEVE randomized clinical trial. JAMA Cardiol. 2024;9(4):323–334. PubMed PMC

Cholesterol Treatment Trialists’ Collaboration. Effects of statin therapy on diagnoses of new-onset diabetes and worsening glycaemia in large-scale randomised blinded statin trials: an individual participant data meta-analysis. Lancet Diabetes Endocrinol. 2024;12(5):306–19. PubMed PMC

Katsiki N, Vrablik M, Banach M, Gouni-Berthold I. Inclisiran, low-density lipoprotein cholesterol and lipoprotein (a). Pharmaceuticals (Basel). 2023;16(4):577. PubMed PMC

Ray KK, Troquay RPT, Visseren FLJ, Leiter LA, Scott Wright R, Vikarunnessa S, Talloczy Z, Zang X, Maheux P, Lesogor A, Landmesser U. Long-term efficacy and safety of inclisiran in patients with high cardiovascular risk and elevated LDL cholesterol (ORION-3): results from the 4-year open-label extension of the ORION-1 trial. Lancet Diabetes Endocrinol. 2023;11(2):109–19. PubMed

Wright RS, Raal FJ, Koenig W, Landmesser U, Leiter LA, Vikarunnessa S, Lesogor A, Maheux P, Talloczy Z, Zang X, Schwartz GG, Ray KK. Inclisiran administration potently and durably lowers LDL-C over an extended-term follow-up: the ORION-8 trial. Cardiovasc Res. 2024. 10.1093/cvr/cvae109. PubMed PMC

Wright RS, Koenig W, Landmesser U, Leiter LA, Raal FJ, Schwartz GG, Lesogor A, Maheux P, Stratz C, Zang X, Ray KK. Safety and tolerability of inclisiran for treatment of hypercholesterolemia in 7 clinical trials. J Am Coll Cardiol. 2023;82(24):2251–61. PubMed

Koren MJ, Rodriguez F, East C, Toth PP, Watwe V, Abbas CA, Sarwat S, Kleeman K, Kumar B, Ali Y, Jaffrani N. An inclisiran first strategy vs usual care in patients with atherosclerosis. J Am Coll Cardiol. 2024;83(20):1939–52. PubMed

Ray KK, Raal FJ, Kallend DG, Jaros MJ, Koenig W, Leiter LA, Landmesser U, Schwartz GG, Lawrence D, Friedman A, Garcia Conde L, Wright RS; ORION Phase III investigators. Inclisiran and cardiovascular events: a patient-level analysis of phase III trials. Eur Heart J. 2023 ;44(2):129–138. PubMed PMC

Bytyci I, et al. Prevalence of statin intolerance: a meta-analysis. Eur Heart J. 2022;43(34):3213–23. PubMed PMC

Banach M. Statin intolerance: time to stop letting it get in the way of treating patients. Lancet. 2022;400(10355):791–3. 10.1016/S0140-6736(22)01643-9. PubMed

Cholesterol Treatment Trialists’ Collaboration. Effect of statin therapy on muscle symptoms: an individual participant data meta-analysis of large-scale, randomised, double-blind trials. Lancet. 2022;400(10355):832-845. PubMed PMC

Ruscica M, Ferri N, Banach M, Sirtori CR, Corsini A. Side effects of statins: from pathophysiology and epidemiology to diagnostic and therapeutic implications. Cardiovasc Res. 2023;118(17):3288–304. PubMed

Banach M, Shekoohi N, Mikhailidis DP, Lip GYH, Hernandez AV, Mazidi M. Relationship between low-density lipoprotein cholesterol, lipid-lowering agents and risk of stroke: a meta-analysis of observational studies (n = 355,591) and randomized controlled trials (n = 165,988). Arch Med Sci. 2022;18(4):912–29. PubMed PMC

Sabouret P, Angoulvant D, Cannon CP, Banach M. Low levels of low-density lipoprotein cholesterol, intracerebral haemorrhage, and other safety issues: is there still a matter of debate? Eur Heart J Open. 2022;2(4):oeac038. PubMed PMC

Goldstein LB, Toth PP, Dearborn-Tomazos JL, Giugliano RP, Hirsh BJ, Peña JM, Selim MH, Woo D; American Heart Association Council on Arteriosclerosis, Thrombosis and Vascular Biology; Council on Cardiovascular and Stroke Nursing; Council on Peripheral Vascular Disease; and Stroke Council. Aggressive LDL-C lowering and the brain: impact on risk for dementia and hemorrhagic stroke: a scientific statement from the American Heart Association. Arterioscler Thromb Vasc Biol. 2023; 43(10):e404–e442. PubMed

Banach M, Cannon CP, Paneni F, Penson PE; endorsed by the International Lipid Expert Panel (ILEP). Individualized therapy in statin intolerance: the key to success. Eur Heart J. 2023;44(7):544–546. PubMed

Penson PE, Pirro M, Banach M. LDL-C: lower is better for longer-even at low risk. BMC Med. 2020;18(1):320. PubMed PMC

Cybulska B, et al. How much should LDL cholesterol be lowered in secondary prevention? Clinical efficacy and safety in the era of PCSK9 inhibitors. Prog Cardiovasc Dis. 2021;67:65–74. PubMed

Ference BA, Ginsberg HN, Graham I, Ray KK, Packard CJ, Bruckert E, Hegele RA, Krauss RM, Raal FJ, Schunkert H, Watts GF, Borén J, Fazio S, Horton JD, Masana L, Nicholls SJ, Nordestgaard BG, van de Sluis B, Taskinen MR, Tokgözoglu L, Landmesser U, Laufs U, Wiklund O, Stock JK, Chapman MJ, Catapano AL. Low-density lipoproteins cause atherosclerotic cardiovascular disease. 1. Evidence from genetic, epidemiologic, and clinical studies. A consensus statement from the European Atherosclerosis Society Consensus Panel. Eur Heart J. 2017;38(32):2459–2472. PubMed PMC

Banach M, Penson PE. Lipid-lowering therapies: better together. Atherosclerosis. 2021;320:86–8. PubMed

Banach M, Penson PE. Statins and LDL-C in secondary prevention-so much progress, so far to go. JAMA Netw Open. 2020;3(11): e2025675. PubMed

National Institute for Health and Care Excellence (NICE), TA733: Inclisiran for treating primary hypercholesterolaemia or mixed dyslipidaemia. 2021.

Mitkowski P, Witkowski A, Stępińska J, Banach M, Jankowski P, Gąsior M, Wita K, Bartuś S, Burchardt P, Farkowski MM, Gierlotka M, Gil R, Leszek P, Sterliński M, Szymański P, Tajstra M, Tycińska A, Wojakowski W. Position of the Polish Cardiac Society on therapeutic targets for LDL cholesterol concentrations in secondary prevention of myocardial infarctions. Kardiol Pol. 2023;81(7–8):818–23. PubMed

Gaudet D, et al. Safety and efficacy of alirocumab in a real-life setting: the ODYSSEY APPRISE study. Eur J Prev Cardiol. 2022;28(17):1864–72. PubMed

Banach M, Lewek J, Pol K, Rabczenko D, Balanescu SM, Blaha V, Ceska R, Jankowski P, Surma S, Kolovou G, Liberopoulos E, Mitu F, Mitu M, Naji FH, Paragh G, Popławska M, Vrablik M, Pella D. Regional differences in physicians’ behavior and factors influencing the intensity of PCSK9 inhibitor therapy with alirocumab: a subanalysis of the ODYSSEY APPRISE study. Front Cardiovasc Med. 2023;10:1206551. PubMed PMC

Nissen SE. Statin denial: an internet-driven cult with deadly consequences. Ann Intern Med. 2017;167(4):281–2. PubMed

Penson PE, Banach M. Nocebo/drucebo effect in statin-intolerant patients: an attempt at recommendations. Eur Heart J. 2021;42(47):4787–8. PubMed

Katsiki N, et al. Statin loading in cardiovascular surgery: never too early to treat. Curr Opin Cardiol. 2018;33(4):436–43. PubMed

Wita K, et al. Managed care after acute myocardial infarction (MC-AMI) reduces total mortality in 12-month follow-up-results from a poland’s national health fund program of comprehensive post-MI Care-a population-wide analysis. J Clin Med. 2020;9(10):3178. PubMed PMC

Jankowski P, Topór-Mądry R, Gąsior M, Cegłowska U, Eysymontt Z, Gierlotka M, Wita K, Legutko J, Dudek D, Sierpiński R, Pinkas J, Kaźmierczak J, Witkowski A, Szumowski Ł. Innovative managed care may be related to improved prognosis for acute myocardial infarction survivors. Circ Cardiovasc Qual Outcomes. 2021;14(8): e007800. PubMed

Diaz R, et al. Intensity of statin treatment after acute coronary syndrome, residual risk, and its modification by alirocumab: insights from the ODYSSEY OUTCOMES trial. Eur J Prev Cardiol. 2021;28(1):33–43. PubMed

Banach M, Penson PE. What have we learned about lipids and cardiovascular risk from PCSK9 inhibitor outcome trials: ODYSSEY and FOURIER? Cardiovasc Res. 2019;115(3):e26–31. PubMed

Solnica B, Sygitowicz G, Sitkiewicz D, Jóźwiak J, Kasperczyk S, Broncel M, et al. 2024 Guidelines of the Polish Society of Laboratory Diagnostics and the Polish Lipid Association on laboratory diagnostics of lipid metabolism disorders. Arch Med Sci. 2024;20(2):357–74. 10.5114/aoms/186191. PubMed PMC

Reiner Z. Why might visit-to visit variability of lipoproteins have an effect on cardiovascular events? Atherosclerosis. 2020;312:99–100. PubMed

GBD 2021 Diabetes Collaborators. Global, regional, and national burden of diabetes from 1990 to 2021, with projections of prevalence to 2050: a systematic analysis for the Global Burden of Disease Study 2021. Lancet. 2023;402(10397):203–234. PubMed PMC

NCD Risk Factor Collaboration (NCD-RisC). Worldwide trends in underweight and obesity from 1990 to 2022: a pooled analysis of 3663 population-representative studies with 222 million children, adolescents, and adults. Lancet. 2024;403(10431):1027–1050. PubMed PMC

Gaita L, Timar B, Timar R, Fras Z, Gaita D, Banach M. Lipid Disorders Management Strategies (2024) in Prediabetic and Diabetic Patients. Pharmaceuticals (Basel). 2024;17(2):219. PubMed PMC

Banach M, Surma S, Toth PP; endorsed by the International Lipid Expert Panel (ILEP). 2023: The year in cardiovascular disease - the year of new and prospective lipid lowering therapies. Can we render dyslipidemia a rare disease by 2024? Arch Med Sci. 2023;19(6):1602–1615. PubMed PMC

Sabouret P, Lemesle G, Bellemain-Appaix A, Aubry P, Bocchino PP, Rafflenbeul E, Belle L, Nolan J, Bernardi M, Biondi-Zoccai G, Savage MP, Banach M, Cayla G. Post-discharge and long-term follow-up after an acute coronary syndrome: International Collaborative Group of CNCF position paper. Arch Med Sci. 2022;18(4):839–54. PubMed PMC

Lp(a)-Lowering Agents in Development: A New Era in Tackling the Burden of Cardiovascular Risk?