Atherosclerosis Supplements 42 (2020) e65ee71 Contents lists available at ScienceDirect Atherosclerosis Supplements journal homepage: www.elsevier.com/locate/atherosclerosis Improving lipid management in patients with acute coronary syndrome: The ACS Lipid EuroPath tool Alessandro Sionis a, *, Alberico L. Catapano b, **, Gaetano M. De Ferrari c, Dariusz Dudek d, J. Wouter Jukema e, Ulf Landmesser f, Angela Pirillo g, François Schiele h, Azfar Zaman i, Jose L. Zamorano j a Intensive Cardiac Care Unit, Cardiology Department, Hospital de La Santa Creu I Sant Pau, Biomedical Research Institute IIB-SantPau, Universidad Autonoma de Barcelona, Barcelona, And Centro de Investigacio n Biom edica en Red Enfermedades Cardiovasculares (CIBERCV), Instituto Carlos III, Madrid, Spain b Department of Pharmacological and Biomolecular Sciences, University of Milan, Milan, IRCCS MultiMedica, Sesto S. Giovanni, Milan, Italy c Department of Medical Sciences, Division of Cardiology, Azienda Ospedaliero Universitaria Citta  Della Salute e Della Scienza di Torino, Torino, Italy d Jagiellonian University Hospital, Krakow, Poland e Department of Cardiology, Leiden University Medical Center, Leiden, And Netherlands Heart Institute, Utrecht, the Netherlands f Department of Cardiology, Charit e University Medicine Berlin, German Center for Cardiovascular Research (DZHK), Partner Site Berlin, Berlin Institute of Health (BIH), Berlin, Germany g Center for the Study of Atherosclerosis, E. Bassini Hospital, Cinisello Balsamo, Milan, and IRCCS MultiMedica, Sesto S. Giovanni, Milan, Italy h CHU of Besançon, Cardiology Department, Besançon, France i Newcastle Upon Tyne Hospital NHS Foundation Trust, Freeman Hospital, And Newcastle University, Newcastle Upon Tyne, UK j Servicio de Cardiología, Hospital Ramon y Cajal, Madrid, Spain a b s t r a c t Keywords: Post-acute coronary syndrome (ACS) patients are at very high risk for recurrent events and mortality, Acute coronary syndrome despite the availability of effective pharmacological approaches. In 2018, the ACS EuroPath Survey, Dyslipidemia performed in collaboration with 555 European cardiologists, identified a sub-optimal LDL-C management Lipids Guidelines in post-ACS patients. Self-assessment Based on these premises, the ACS EuroPath II project led to the development of a self-assessment tool to improve lipid management in these very high risk patients, taking into consideration the new 2019 ESC/EAS guidelines. This tool is built in 3 sections. The first is a questionnaire to assess the lipid man- agement practice from the acute phase up to 12 months of follow-up. The main topics covered in this section relate to 1) acute phase (lipid management of ACS patients during hospitalization; 2) discharge (lipid management at discharge, with focus on follow-up plan); 3) follow-up (lipid management at the time of first and subsequent follow-ups); 4) referral pathway for definitive lipid management care of post-ACS patients; 5) evaluation of the achieved goal at 6 months to 1 year and key implications. The second section is a brief report to position the results against other European Union clinical practice and European guidelines. The last section allows the physician to evaluate and consider the implementation of one or more strategies, successfully developed in leading European centers, in order to optimize their own clinical practice. © 2021 The Authors. Published by Elsevier B.V. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). 1. Introduction * Corresponding author. Intensive Cardiac Care Unit, Cardiology Department, Acute coronary syndrome (ACS) patients remain at very high Hospital de la Santa Creu i Sant Pau, Biomedical Research Institute IIB-SantPaul, Universidad Autonoma de Barcelona, Barcelona, Spain. risk for recurrent events and mortality, despite availability of ** Corresponding author. Department of Pharmacological and Biomolecular Sci- effective pharmacological approaches [1,2]. In 2018, the ACS Euro- ences, University of Milan and IRCCS Multimedica Via Balzaretti, 9 - 20133, Milan, Path I survey, performed in collaboration with 555 European car- Italy. diologists and 2775 patient records, demonstrated a sub-optimal E-mail addresses: asionis@santpau.cat (A. Sionis), alberico.catapano@unimi.it LDL-C management after ACS [3]. However, multiple initiatives (A.L. Catapano). https://doi.org/10.1016/j.atherosclerosissup.2021.01.011 1567-5688/© 2021 The Authors. Published by Elsevier B.V. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). A. Sionis, A.L. Catapano, G.M. De Ferrari et al. Atherosclerosis Supplements 42 (2020) e65ee71 Fig. 1. Lipid profile management of ACS patients during the acute phase (hospitalization). from several European countries have shown that the imple- questionnaire, a report, and potential targets for optimization. mentation of robust algorithms/protocols for LDL-C management can result in a more effective translation of guideline recommen- dations into clinical practice and significantly increase the 4. Questionnaire achievement of recommended LDL-C goals to reduce CV risk [4]. Based on these premises, the ACS EuroPath project led to the The questionnaire allows the physician to insert patient infor- development of a self-assessment tool for physicians aimed at mation from acute admission to the follow-up phase and comprises identifying potential areas of improvement in the management of four distinct sections: 1) acute phase (lipid management of ACS these very high risk patients, taking into consideration the rec- patients during hospitalization; 2) discharge (lipid management at ommendations provided by the new 2019 ESC/EAS guidelines [5]. discharge, with focus on follow-up plan); 3) follow-up (lipid This self-assessment tool has been developed in collaboration with management at the time of first and subsequent follow-ups); 4) a team of 8 European cardiologists and lipidologists and is pre- referral pathway for lipid management of post-ACS patients; 5) sented in this article. evaluation of the achieved goal at 6 months to 1 year and key implications. The acute phase section includes practices regarding lipid 2. Objectives of the self-assessment tool testing, lipid lowering therapy (with distinction between statin- naïve patients and patients already on statin at admission), and The objectives of the self-assessment tool are to: 1) provide a practices regarding the screening for heterozygous familial hyper- snapshot of clinical practice at a given time (it does not require cholesterolemia (FH). Physicians must indicate when the LDL-C identifiable patient related data). It is based on simple questions to level is assessed, for what percentage of ACS patient LDL-C level assess personal practice regarding post ACS lipid management. The is assessed at admission, and additional parameters evaluated tool is quick to use and data are only for personal use of the (including total cholesterol, non-HDL-C, Lp(a), and glycaemia physician, 2) position the results with regard to current European among others) during the acute phase (Fig. 1). Information clinical practice as highlighted by the 2018 ACS EuroPath I survey regarding lipid-lowering therapy at admission is collected. For [3], and 3) help identify strengths and areas of optimization by statin naïve patients, physicians must indicate when the lipid- comparing to current European guidelines and European local lowering treatment is started after admission, the percentage of clinical practice. patients receiving high intensity statin post-event, and whether ezetimibe on top of statin is considered in specific subgroup of 3. Key topics covered by the self-assessment tool patients. For patients already on statin before the event, physicians should indicate the percentage of patients who had a lipid- The key topics covered in the self-assessment tool relate to the lowering therapy intensification, the type of treatment intensifi- management of lipids in ACS patients from the hospitalization cation (dose increase, dose doubling, adding ezetimibe on top of phase and during follow-up and has been organized in 3 sections: a maximally tolerated dose of statin, initiate PCSK9i, etc.), and when 66 A. Sionis, A.L. Catapano, G.M. De Ferrari et al. Atherosclerosis Supplements 42 (2020) e65ee71 Fig. 2. Lipid profile management of ACS patients at discharge. the treatment is adjusted with regard to admission time (Fig. 1). A ACS patients compared with the general population, the EuroPath I special section in the questionnaire is dedicated to the detection of survey showed that only 18% of patients hospitalized for an ACS patients with FH. Based on recommendations by ESC/EAS guide- were screened for FH during the acute phase (Landmesser et al.) [3]. lines and the data provided by surveys in ACS patients (refs), phy- The discharge section focuses on four specific points: 1) follow- sicians are asked to provide information on whether a screening up plan, 2) LDL-C goal at discharge, 3) discharge letter addressed to protocol is applied in patients hospitalized for an ACS, and the the general practitioner (GP) involved in this phase, and 4) infor- clinical criteria considered for the screening (in particular age, mation provided to patients (Fig. 2). ESC/EAS guidelines recom- family history of CVD, elevated lipid levels, and the clinical score mend that ACS patients participate in a structured cardiac used) (Fig. 1). This represents a significant point since, although rehabilitation program, in order to improve adequate control of several surveys have reported an increased incidence of FH among cardiovascular risk factors including lipid levels and improve Fig. 3. Lipid profile management of ACS patients after discharge (follow-up phase). 67 A. Sionis, A.L. Catapano, G.M. De Ferrari et al. Atherosclerosis Supplements 42 (2020) e65ee71 Fig. 4. Referral pathway for definitive lipid management of ACS patients. overall survival following the acute event [6]. Of note, in the reached, the timing for future follow-up visits) (Fig. 2). Finally, EuroPath I survey, only half of the patients had a rehabilitation/ details on the information provided to the patient at discharge are secondary prevention program planned during follow-up [3]. In also required, including indications on LDL-C goal, follow-up visit this section, physicians are required to insert information regarding plan (including lipid profile monitoring), and lifestyle interventions the follow-up planning, including participation in a rehabilitation (such as sport and diet) (Fig. 2). program, and the indication of the LDL-C goal. Furthermore, details The follow-up section includes information on lipid manage- on the indications included in the discharge letter must be stated ment practice at the time of the first follow-up visit and subsequent (including the LDL-C goal, time to next LDL-C evaluation, the follow-ups (Fig. 3). This section focuses on the intensification of pharmacological approach to be adopted in case LDL-C goal is not lipid-lowering therapy in those patients who did not achieve their Fig. 5. Outcomes at 6 months to 1 year. 68 A. Sionis, A.L. Catapano, G.M. De Ferrari et al. Atherosclerosis Supplements 42 (2020) e65ee71 LDL-C goal, and requires information on the clinical criteria approach with these patients (Fig. 5). considered for therapy intensification (such as lipid levels, indi- vidual CV risk profile, therapy tolerance) as well as the type of 5. Report treatment intensification adopted (increase of statin dose, adding ezetimibe to the same statin dose or on top of the maximally This second part of the tool is a brief report allowing to position tolerated dose, initiating a PSCK9 inhibitor). Furthermore, the the results obtained in each single section with respect to either the timing of intensification of the therapy is required (Fig. 3). latest European guidelines or other European countries (as an The fourth section is focused on the referral pathway for lipid example of current practice) (Fig. 6). This will allow the physician to management of post-ACS patients, with special attention for pa- define the capability of the local pathway for the lipid management tients suspected of FH, statin-intolerant patients, patients eligible of ACS patients to follow these high CV risk patients with the most for a PCSK9 inhibitor, patients at high risk due to the presence of appropriate approach and to achieve the lipid goal defined for their risk factors such as polyvascular disease, elevated LDL-C, diabetes, CV risk category. recurrent CV events, kidney disease or previous stroke (Fig. 4). The last section requires information on the LDL-C levels ach- ieved at 6 months to 1 year, and offers the opportunity to indicate 6. Next step which part of the local pathway should be refined or optimized, with the aim of further refining the application of the appropriate The last section allows physicians to suggest actions to be implemented in order to further optimize the management of ACS Fig. 6. Positioning of results with regards to other EU clinical practice stemming from the ACS Patient Pathway Project survey and the ESC/EAS Guidelines-An example. 69 A. Sionis, A.L. Catapano, G.M. De Ferrari et al. Atherosclerosis Supplements 42 (2020) e65ee71 patients. CRediT authorship contribution statement Evaluation of the ACS Lipid EuroPath tool by practicing physi- cians revealed that 80% found the tool useful, and 74% found the Alessandro Sionis: Conceptualization, Methodology, Investiga- tool easy to use; the possibility to compare clinical practice to the tion, Supervision. Alberico L. Catapano: Conceptualization, Meth- ACS EuroPath survey and to the dyslipidaemias guidelines was odology, Investigation, Supervision. Gaetano M. De Ferrari: judged as positive by 75%. Conceptualization, Supervision, Methodology, Investigation. Dariusz Dudek: Conceptualization, Supervision, Methodology, 7. Discussion Investigation. J. Wouter Jukema: Conceptualization, Supervision, Methodology, Investigation. Angela Pirillo: Writing - Original Post-ACS patients are at high risk of recurrent events and thus Draft, Writing - Review & Editing, Visualization François Schiele: require a targeted pharmacological approach for optimal manage- Conceptualization, Supervision, Methodology, Investigation. Azfar ment of underlying risk factors. Hypercholesterolaemia represents Zaman: Conceptualization, Supervision, Methodology, Investiga- a major risk factor in these patients, as several studies have shown tion. Jose L. Zamorano: Conceptualization, Supervision, Method- that in clinical practice the achievement of the guidelines recom- ology, Investigation. mended LDL-C goal is obtained in a low percentage of patients (ref) [3,7]. This may be related to a broad range of factors; among them, Declaration of competing interest the lack of common tools defining specific key steps for the man- agement of patients with an ACS during the hospitalization (acute AS or his department have received research grants and/or phase), at discharge, and at follow-up. The tool presented has been speaker honoraria from Amgen, Astra-Zeneca, Dalcor, Daichii- created with the aim to fill this gap, and to provide the physician Sankyo, Esperion, Ferrer, Novartis, Orion-Pharma, Pfizer, Sanofi with an instrument to optimize and improve lipid management in Aventis, Servier, Sphingotech, Singulex and Zoll; additionally from high CV risk patients. Furthermore, by comparing the results ob- the following agencies: Sociedad Espan ~ ola de Cardiología; Instituto tained by the physician with other examples of current practice de Salud Carlos III (ISCIII). ALC reports grants from Amgen, Sanofi, would help define areas that can be potentially improved either at Regeneron personal fees from Merck, Sanofi, Regeneron, AstraZe- the individual or local level. neca, Amgen, Novartis, outside the submitted work. GDF has The development of this tool is based on the experience of received research grant support from Amgen, Merck, and Novartis; previous studies. The ACS Patient Pathway Project (EuroPath I) has served as a consultant for Amgen, Boston Scientific, Livanova, survey was performed in 7 European countries with the aim of Merck, and Sigma-Tau; and received lecturing fees from Amgen, evaluating compliance to the recommendations from current ESC/ Merck, and Sigma-Tau. DD has nothing to disclose. JWJ/his EAS guidelines for the management of ACS patients and the effec- department has received research grants from and/or was speaker tiveness of secondary prevention in this high CV risk population [3]. (with or without lecture fees) on a.o.(CME accredited) meetings The results showed that lipid management is still suboptimal sponsored by Amgen, Athera, Astra-Zeneca, Biotronik, Boston Sci- despite the availability of highly effective lipid-lowering drugs, entific, Dalcor, Daiichi Sankyo, Lilly, Medtronic, Merck-Schering- which exposes these patients to high risk of recurrent events. On Plough, Pfizer, Roche, Sanofi Aventis, The Medicine Company, the the other hand, European initiatives in which local algorithms Netherlands Heart Foundation, CardioVascular Research the specific for ACS patients have been routinely applied successfully, Netherlands (CVON), the Netherlands Heart Institute and the Eu- translated into a significantly higher achievement of LDL-C goals ropean Community Framework KP7 Programme. UL reports grant due to the presence of lipid teams to which patients are referred to support from Bayer and Novartis, and lecture honoraria from after discharge and the wide use of high intensity lipid-lowering AstraZeneca, Amgen, Bayer, Sanofi, Berlin Chemie, Novartis, Abbott, therapies [4]. For these reasons, attention is drawn to the contin- and the Medicines Company. AP has nothing to disclose. FS has uous evaluation of the lipid profile and lipid-lowering therapies at received research grants and/or speaker honoraria from: Amgen, all stages (acute phase, discharge, and follow-up), as the benefits of Astra-Zeneca, Bayer, Dalcor, Lilly, Novonordisk, MSD, Mylan, statins in secondary prevention have been unequivocally demon- Novartis, Sanofi Aventis, Servier and Terumo. AZ has received strated, and a large number of trials have shown the benefits of consulting fees from Miracor. JLZ reports research grants from early and intensive statin therapy in ACS [6]. The relevance of the Abbott and speaker honoraria from Bayer, Pfizer, and Daichii. lipid-lowering approach in ACS patients has also been reviewed by the most recent ESC/EAS guidelines in which the addition of a Acknowledgments PCSK9 inhibitor to current therapy is recommended when the LDL- C goal is not achieved after 4e6 weeks despite maximal tolerated The presentation of data contained in this work at the annual statin therapy and ezetimibe [5]. meeting of SITeCS (Societ a Italiana di Terapia Clinica e Sper- Furthermore, there is emphasis on the importance of the role of imentale) was realized with the institutional support of Sanofi. The screening for FH in ACS patients. In fact, although it is known that sponsor of this activity had no role in the design, interpretation, this inherited condition is common in the general population decision to publish, or writing the manuscript. The work of ALC has (~1:250) [8] and is even more common among ACS patients [9e13], been supported by Ministry of Health - Ricerca Corrente - IRCCS several studies provided evidence that FH screening within ACS MultiMedica, PRIN 2017H5F943 and ERANET ER-2017-2364981. patient population remains largely unapplied. FH confers by itself a This article is part of a Supplement entitled “Plasma lipids and high- or very-high CV risk, and, due to the lifelong exposure to cardiovascular risk: Nutritional and therapeutic approaches” pub- elevated levels of LDL-C, the occurrence of cardiovascular events at lished with support from Societa  Italiana di Terapia Clinica e an early age compared with the general population must alert the Sperimentale (SITeCS). cardiologist to start a specific pathway for the correct diagnosis and the appropriate pharmacological approach. 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