Guideline-adherent secondary prevention post-acute coronary syndromes: the importance of patient uptake and persistence

Guideline-adherent secondary prevention post-acute coronary syndromes: the importance of patient... This editorial refers to ‘Differences in initiation and discontinuation of preventive medications and use of non-pharmacological interventions after acute coronary syndrome among migrants and Danish born’, by H.W. Frederiksen et al., doi:10.1093/eurheartj/ehy227. Despite significant improvements over the last two decades in the acute management of patients presenting with acute coronary syndromes (ACS) with the widespread adoption of primary percutaneous coronary intervention, long-term management remains challenging.1 The morbidity burden after ACS is high, as ∼20% of survivors experience a subsequent cardiovascular event (recurrent myocardial infarction, stroke, or cardiovascular death) during the first 24 months,2 and total mortality rates vary between 19% and 22% by 5 years of follow-up.3 Residual cardiovascular risk and high rates of recurrent events generally lead to poor long-term prognosis.4 Thus, adequate secondary prevention after ACS is crucial in order to prevent further cardiovascular events, disease progression, and death, and to improve length and quality of life. Current European guidelines recommend long-term secondary prevention through optimized pharmacological treatments with anti-thrombotic drugs, beta-blockers, lipid-lowering therapy, renin–angiotensin system inhibitors, and comprehensive lifestyle interventions with risk factor management and cardiac rehabilitation.5,6 Since adherence to long-term evidence-based therapies among cardiovascular patients is generally poor,7 implementation of innovative strategies and multidisciplinary approaches that may enhance adherence, and identification of patients with high risk of non-adherence should be a priority.8 When investigating the persistence with secondary prevention medication in the TRANSLATE-ACS study (prospective observational multicentre study), nearly one-third of the 7955 patients discontinued the prescribed medication by 6 months after ACS.9 In this issue of the journal, Frederiksen et al.10 report their findings from a large, nationwide population-based study, which assessed ethnic differences in the use of preventive pharmacological treatment and non-pharmacological interventions among survivors of ACS by comparing migrants and Danish-born citizens. From the Danish national registries, they identified 33 199 patients who were discharged from hospital following ACS during 2010–2014, and examined the initiation rates and time to discontinuation of secondary preventive medications, in addition to participation in cardiac rehabilitation programmes, determined by the number of contacts for the interventions during a 180-day follow-up. They found significantly lower initiation rates of both pharmaceutical treatment and lifestyle interventions in non-Western migrants (Turks and Pakistanis) compared with Danish-born citizens, whereas Western migrants did not differ significantly from those who were Danish born. The risk of therapy discontinuation was found to be significantly higher for all medication groups in non-Western migrants compared with those who were Danish born. For non-pharmacological interventions, all migrant subgroups showed statistically lower participation. The study by Frederiksen et al. has many positive aspects, including a large cohort size, statistical power, and a comprehensive assessment on the use of both pharmacological and lifestyle-changing interventional measures. Their findings are some of the first European real-world data on treatment adherence and persistence with secondary prevention post-ACS among migrants, shifting the focus onto the causative factors and possible interventional strategies that may enhance patient adherence. Nevertheless, as with most observational studies based on administrative data, there are several limitations that should be recognized.11 For example, there are no data about follow-up visits or monitoring; no evidence about post-discharge evolution of the disease or treatment-associated complications; no data on the presence of new-onset disease(s) which may explain possible contraindications to secondary prevention treatment; no information about patient education and psychological adaptation; and no adjustment for bias and residual confounders from co-morbidities. These finding serve as a reminder that due to mass immigration and significant demographic changes in populations, healthcare systems throughout Europe need to adapt, and some ethnic groups may require closer attention and/or specific interventions for both primary and secondary prevention of ACS. The reasons for the differences in treatment initiation and persistence, and participation in non-pharmacological interventions, requires further exploration. It is not possible to ascertain from the nationwide registries if migrants were less likely to be prescribed non-pharmacological lifestyle interventions due to physician-perceived barriers or patient refusal. In the study of Frederiksen et al.,10 non-Western migrants had less formal education compared with Danish-born citizens, and this, along with possible language barriers and socio-economic factors [i.e. availability of disposable income to participate in required lifestyle changes, healthier food options, access to leisure/exercise facilities, ability to take time off work to attend cardiac rehabilitation (non-Western migrants were of working age), and financial contribution to medication (as only part-coverage, etc.)], may have contributed to the lower rates of initiation and adherence to secondary prevention among non-Western migrants. Language barriers significantly impair the ability of healthcare professionals to impart patient education and explain the necessity of medication and lifestyle change to patients. Understanding the reasons for the reported differences is important to target interventions appropriately; it may be more beneficial to target public health interventions, for primary and secondary prevention, of the whole Danish population rather than focusing resources specifically on one group (migrants), but it may be that group-specific interventions are required. In contrast, real-world data about adherence to and persistence with treatments in other chronic conditions, such as oral anticoagulation for stroke prevention in atrial fibrillation (AF), are more variable. High early vitamin K antagonist (VKA) discontinuation rates in some vulnerable patient groups (e.g. the elderly, cardiovascular and malignant co-morbidities, and renal failure) still remain an area of concern, as cessation has been associated with poor clinical outcomes.12 In the era of non-vitamin K oral anticoagulants (NOACs), guideline adherence has improved significantly, leading to higher therapy persistence with NOACs than with VKAs, when compared in a large British cohort of anticoagulation-naïve patients with non-valvular AF.13 This emphasizes the importance of patient education and proposes a well-structured follow-up system, which may serve as a practical model for implementation of, and to improve, cardiovascular treatment adherence in other fields.14 For future considerations, it is essential to identify health system-related difficulties and weaknesses in the management and support of secondary prevention post-ACS discharge, but socio-economic- and patient-related factors including education level, language barriers, immigrant status, and financial concerns should also be taken into consideration to optimize treatment adherence (Take home figure). Proper utilization of and adherence to evidence-based treatment strategies and interventions has to be the priority after ACS in order to improve long-term outcomes. Take home figure View largeDownload slide Strategies to improve patients’ treatment adherence and persistence. Take home figure View largeDownload slide Strategies to improve patients’ treatment adherence and persistence. Conflict of interest: Dr Székely has no conflict of interest to declare. Dr Lane has received investigator-initiated educational grants from Bristol-Myers Squibb and Boehringer Ingelheim, has been a speaker for Boehringer Ingelheim, Bayer, and Bristol-Myers Squibb/Pfizer, and has consulted for Bristol-Myers Squibb, Bayer, and Boehringer Ingelheim. Professor Lip has been a consultant for Bayer/Janssen, Bristol-Myers Squibb/Pfizer, Biotronik, Medtronic, Boehringer Ingelheim, Microlife, and Daiichi-Sankyo, and a speaker for Bayer, Bristol-Myers Squibb/Pfizer, Medtronic, Boehringer Ingelheim, Microlife, Roche, and Daiichi-Sankyo. References 1 Sibbing D, Angiolillo DJ, Huber K. Antithrombotic therapy for acute coronary syndrome: past, present and future. Thromb Haemost  2017; 117: 1240– 1248. Google Scholar CrossRef Search ADS PubMed  2 Jernberg T, Hasvold P, Henriksson M, Hjelm H, Thuresson M, Janzon M. Cardiovascular risk in post-myocardial infarction patients: nationwide real world data demonstrate the importance of a long-term perspective. Eur Heart J  2015; 36: 1163– 1170. Google Scholar CrossRef Search ADS PubMed  3 Fox KAA, Carruthers KF, Dunbar DR, Graham C, Manning JR, De Raedt H, Buysschaert I, Lambrechts D, Van de Werf F. Underestimated and under-recognized: the late consequences of acute coronary syndrome (GRACE UK-Belgian Study). Eur Heart J  2010; 31: 2755– 2764. Google Scholar CrossRef Search ADS PubMed  4 Piironen M, Ukkola O, Huikuri H, Havulinna AS, Koukkunen H, Mustonen J, Ketonen M, Lehto S, Airaksinen J, Antero Kesäniemi Y, Salomaa V. Trends in long-term prognosis after acute coronary syndrome. Eur J Prev Cardiol  2017; 24: 274– 280. Google Scholar CrossRef Search ADS PubMed  5 Ibanez B, James S, Agewall S, Antunes MJ, Bucciarelli-Ducci C, Bueno H, Caforio ALP, Crea F, Goudevenos JA, Halvorsen S, Hindricks G, Kastrati A, Lenzen MJ, Prescott E, Roffi M, Valgimigli M, Varenhorst C, Vranckx P, Widimský P; ESC Scientific Document Group. 2017 ESC Guidelines for the management of acute myocardial infarction in patients presenting with ST-segment elevation. Eur Heart J  2018; 39: 119– 177. Google Scholar CrossRef Search ADS PubMed  6 Roffi M, Patrono C, Collet J-P, Mueller C, Valgimigli M, Andreotti F, Bax JJ, Borger MA, Brotons C, Chew DP, Gencer B, Hasenfuss G, Kjeldsen K, Lancellotti P, Landmesser U, Mehilli J, Mukherjee D, Storey RF, Windecker S; ESC Scientific Document Group. 2015 ESC Guidelines for the management of acute coronary syndromes in patients presenting without persistent ST-segment elevation. Eur Heart J  2015; 32: 2999– 3054. 7 Naderi SH, Bestwick JP, Wald DS. Adherence to drugs that prevent cardiovascular disease: meta-analysis on 376,162 patients. Am J Med  2012; 125: 882– 887. Google Scholar CrossRef Search ADS PubMed  8 Piepoli MF, Corrà U, Abreu A, Cupples M, Davos C, Doherty P, Höfer S, Garcia-Porrero E, Rauch B, Vigorito C, Völler H, Schmid JP; Cardiac Rehabilitation Section of the European Association for Cardiovascular Prevention & Rehabilitation of the ESC. Challenges in secondary prevention of cardiovascular diseases: a review of the current practice. Int J Cardiol  2015; 180: 114– 119. Google Scholar CrossRef Search ADS PubMed  9 Mathews R, Wang TY, Honeycutt E, Henry TD, Zettler M, Chang M, Fonarow GC, Peterson ED; TRANSLATE-ACS Study Investigators. Persistence with secondary prevention medications after acute myocardial infarction: insights from the TRANSLATE-ACS study. Am Heart J  2015; 170: 62– 69. Google Scholar CrossRef Search ADS PubMed  10 Frederiksen HW, Zwisler A-D, Johnsen SP, Öztürk B, Lindhardt T, Norredam M. Differences in initiation and discontinuation of preventive medications and use of non- pharmacological interventions after acute coronary syndrome among migrants and Danish born. Eur Heart J  2018; 39:doi:10.1093/eurheartj/ehy227. 11 Freedman B, Lip GYH. ‘Unreal world’ or ‘real world’ data in oral anticoagulant treatment of atrial fibrillation. Thromb Haemost  2016; 116: 587– 589. Google Scholar CrossRef Search ADS PubMed  12 Rivera-Caravaca JM, Roldán V, Esteve-Pastor MA, Valdés M, Vicente V, Lip GYH, Marin F. Cessation of oral anticoagulation is an important risk factor for stroke and mortality in atrial fibrillation patients. Thromb Haemost  2017; 117: 1448– 1454. Google Scholar CrossRef Search ADS PubMed  13 Martinez C, Katholing A, Wallenhorst C, Freedman SB. Therapy persistence in newly diagnosed non-valvular atrial fibrillation treated with warfarin or NOAC. A cohort study. Thromb Haemost  2016; 115: 31– 39. Google Scholar CrossRef Search ADS PubMed  14 Steffel J, Verhamme P, Potpara TS, Albaladejo P, Antz M, Desteghe L, et al.   The 2018 European Heart Rhythm Association Practical Guide on the use of non-vitamin K antagonist oral anticoagulants in patients with atrial fibrillation. Eur Heart J  2018; 39: 1330– 1393. Google Scholar CrossRef Search ADS PubMed  Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2018. For permissions, please email: journals.permissions@oup.com. This article is published and distributed under the terms of the Oxford University Press, Standard Journals Publication Model (https://academic.oup.com/journals/pages/about_us/legal/notices) http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png European Heart Journal Oxford University Press

Guideline-adherent secondary prevention post-acute coronary syndromes: the importance of patient uptake and persistence

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Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2018. For permissions, please email: journals.permissions@oup.com.
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Abstract

This editorial refers to ‘Differences in initiation and discontinuation of preventive medications and use of non-pharmacological interventions after acute coronary syndrome among migrants and Danish born’, by H.W. Frederiksen et al., doi:10.1093/eurheartj/ehy227. Despite significant improvements over the last two decades in the acute management of patients presenting with acute coronary syndromes (ACS) with the widespread adoption of primary percutaneous coronary intervention, long-term management remains challenging.1 The morbidity burden after ACS is high, as ∼20% of survivors experience a subsequent cardiovascular event (recurrent myocardial infarction, stroke, or cardiovascular death) during the first 24 months,2 and total mortality rates vary between 19% and 22% by 5 years of follow-up.3 Residual cardiovascular risk and high rates of recurrent events generally lead to poor long-term prognosis.4 Thus, adequate secondary prevention after ACS is crucial in order to prevent further cardiovascular events, disease progression, and death, and to improve length and quality of life. Current European guidelines recommend long-term secondary prevention through optimized pharmacological treatments with anti-thrombotic drugs, beta-blockers, lipid-lowering therapy, renin–angiotensin system inhibitors, and comprehensive lifestyle interventions with risk factor management and cardiac rehabilitation.5,6 Since adherence to long-term evidence-based therapies among cardiovascular patients is generally poor,7 implementation of innovative strategies and multidisciplinary approaches that may enhance adherence, and identification of patients with high risk of non-adherence should be a priority.8 When investigating the persistence with secondary prevention medication in the TRANSLATE-ACS study (prospective observational multicentre study), nearly one-third of the 7955 patients discontinued the prescribed medication by 6 months after ACS.9 In this issue of the journal, Frederiksen et al.10 report their findings from a large, nationwide population-based study, which assessed ethnic differences in the use of preventive pharmacological treatment and non-pharmacological interventions among survivors of ACS by comparing migrants and Danish-born citizens. From the Danish national registries, they identified 33 199 patients who were discharged from hospital following ACS during 2010–2014, and examined the initiation rates and time to discontinuation of secondary preventive medications, in addition to participation in cardiac rehabilitation programmes, determined by the number of contacts for the interventions during a 180-day follow-up. They found significantly lower initiation rates of both pharmaceutical treatment and lifestyle interventions in non-Western migrants (Turks and Pakistanis) compared with Danish-born citizens, whereas Western migrants did not differ significantly from those who were Danish born. The risk of therapy discontinuation was found to be significantly higher for all medication groups in non-Western migrants compared with those who were Danish born. For non-pharmacological interventions, all migrant subgroups showed statistically lower participation. The study by Frederiksen et al. has many positive aspects, including a large cohort size, statistical power, and a comprehensive assessment on the use of both pharmacological and lifestyle-changing interventional measures. Their findings are some of the first European real-world data on treatment adherence and persistence with secondary prevention post-ACS among migrants, shifting the focus onto the causative factors and possible interventional strategies that may enhance patient adherence. Nevertheless, as with most observational studies based on administrative data, there are several limitations that should be recognized.11 For example, there are no data about follow-up visits or monitoring; no evidence about post-discharge evolution of the disease or treatment-associated complications; no data on the presence of new-onset disease(s) which may explain possible contraindications to secondary prevention treatment; no information about patient education and psychological adaptation; and no adjustment for bias and residual confounders from co-morbidities. These finding serve as a reminder that due to mass immigration and significant demographic changes in populations, healthcare systems throughout Europe need to adapt, and some ethnic groups may require closer attention and/or specific interventions for both primary and secondary prevention of ACS. The reasons for the differences in treatment initiation and persistence, and participation in non-pharmacological interventions, requires further exploration. It is not possible to ascertain from the nationwide registries if migrants were less likely to be prescribed non-pharmacological lifestyle interventions due to physician-perceived barriers or patient refusal. In the study of Frederiksen et al.,10 non-Western migrants had less formal education compared with Danish-born citizens, and this, along with possible language barriers and socio-economic factors [i.e. availability of disposable income to participate in required lifestyle changes, healthier food options, access to leisure/exercise facilities, ability to take time off work to attend cardiac rehabilitation (non-Western migrants were of working age), and financial contribution to medication (as only part-coverage, etc.)], may have contributed to the lower rates of initiation and adherence to secondary prevention among non-Western migrants. Language barriers significantly impair the ability of healthcare professionals to impart patient education and explain the necessity of medication and lifestyle change to patients. Understanding the reasons for the reported differences is important to target interventions appropriately; it may be more beneficial to target public health interventions, for primary and secondary prevention, of the whole Danish population rather than focusing resources specifically on one group (migrants), but it may be that group-specific interventions are required. In contrast, real-world data about adherence to and persistence with treatments in other chronic conditions, such as oral anticoagulation for stroke prevention in atrial fibrillation (AF), are more variable. High early vitamin K antagonist (VKA) discontinuation rates in some vulnerable patient groups (e.g. the elderly, cardiovascular and malignant co-morbidities, and renal failure) still remain an area of concern, as cessation has been associated with poor clinical outcomes.12 In the era of non-vitamin K oral anticoagulants (NOACs), guideline adherence has improved significantly, leading to higher therapy persistence with NOACs than with VKAs, when compared in a large British cohort of anticoagulation-naïve patients with non-valvular AF.13 This emphasizes the importance of patient education and proposes a well-structured follow-up system, which may serve as a practical model for implementation of, and to improve, cardiovascular treatment adherence in other fields.14 For future considerations, it is essential to identify health system-related difficulties and weaknesses in the management and support of secondary prevention post-ACS discharge, but socio-economic- and patient-related factors including education level, language barriers, immigrant status, and financial concerns should also be taken into consideration to optimize treatment adherence (Take home figure). Proper utilization of and adherence to evidence-based treatment strategies and interventions has to be the priority after ACS in order to improve long-term outcomes. Take home figure View largeDownload slide Strategies to improve patients’ treatment adherence and persistence. Take home figure View largeDownload slide Strategies to improve patients’ treatment adherence and persistence. Conflict of interest: Dr Székely has no conflict of interest to declare. Dr Lane has received investigator-initiated educational grants from Bristol-Myers Squibb and Boehringer Ingelheim, has been a speaker for Boehringer Ingelheim, Bayer, and Bristol-Myers Squibb/Pfizer, and has consulted for Bristol-Myers Squibb, Bayer, and Boehringer Ingelheim. Professor Lip has been a consultant for Bayer/Janssen, Bristol-Myers Squibb/Pfizer, Biotronik, Medtronic, Boehringer Ingelheim, Microlife, and Daiichi-Sankyo, and a speaker for Bayer, Bristol-Myers Squibb/Pfizer, Medtronic, Boehringer Ingelheim, Microlife, Roche, and Daiichi-Sankyo. References 1 Sibbing D, Angiolillo DJ, Huber K. Antithrombotic therapy for acute coronary syndrome: past, present and future. Thromb Haemost  2017; 117: 1240– 1248. Google Scholar CrossRef Search ADS PubMed  2 Jernberg T, Hasvold P, Henriksson M, Hjelm H, Thuresson M, Janzon M. Cardiovascular risk in post-myocardial infarction patients: nationwide real world data demonstrate the importance of a long-term perspective. Eur Heart J  2015; 36: 1163– 1170. Google Scholar CrossRef Search ADS PubMed  3 Fox KAA, Carruthers KF, Dunbar DR, Graham C, Manning JR, De Raedt H, Buysschaert I, Lambrechts D, Van de Werf F. Underestimated and under-recognized: the late consequences of acute coronary syndrome (GRACE UK-Belgian Study). Eur Heart J  2010; 31: 2755– 2764. Google Scholar CrossRef Search ADS PubMed  4 Piironen M, Ukkola O, Huikuri H, Havulinna AS, Koukkunen H, Mustonen J, Ketonen M, Lehto S, Airaksinen J, Antero Kesäniemi Y, Salomaa V. Trends in long-term prognosis after acute coronary syndrome. Eur J Prev Cardiol  2017; 24: 274– 280. Google Scholar CrossRef Search ADS PubMed  5 Ibanez B, James S, Agewall S, Antunes MJ, Bucciarelli-Ducci C, Bueno H, Caforio ALP, Crea F, Goudevenos JA, Halvorsen S, Hindricks G, Kastrati A, Lenzen MJ, Prescott E, Roffi M, Valgimigli M, Varenhorst C, Vranckx P, Widimský P; ESC Scientific Document Group. 2017 ESC Guidelines for the management of acute myocardial infarction in patients presenting with ST-segment elevation. Eur Heart J  2018; 39: 119– 177. Google Scholar CrossRef Search ADS PubMed  6 Roffi M, Patrono C, Collet J-P, Mueller C, Valgimigli M, Andreotti F, Bax JJ, Borger MA, Brotons C, Chew DP, Gencer B, Hasenfuss G, Kjeldsen K, Lancellotti P, Landmesser U, Mehilli J, Mukherjee D, Storey RF, Windecker S; ESC Scientific Document Group. 2015 ESC Guidelines for the management of acute coronary syndromes in patients presenting without persistent ST-segment elevation. Eur Heart J  2015; 32: 2999– 3054. 7 Naderi SH, Bestwick JP, Wald DS. Adherence to drugs that prevent cardiovascular disease: meta-analysis on 376,162 patients. Am J Med  2012; 125: 882– 887. Google Scholar CrossRef Search ADS PubMed  8 Piepoli MF, Corrà U, Abreu A, Cupples M, Davos C, Doherty P, Höfer S, Garcia-Porrero E, Rauch B, Vigorito C, Völler H, Schmid JP; Cardiac Rehabilitation Section of the European Association for Cardiovascular Prevention & Rehabilitation of the ESC. Challenges in secondary prevention of cardiovascular diseases: a review of the current practice. Int J Cardiol  2015; 180: 114– 119. Google Scholar CrossRef Search ADS PubMed  9 Mathews R, Wang TY, Honeycutt E, Henry TD, Zettler M, Chang M, Fonarow GC, Peterson ED; TRANSLATE-ACS Study Investigators. Persistence with secondary prevention medications after acute myocardial infarction: insights from the TRANSLATE-ACS study. Am Heart J  2015; 170: 62– 69. Google Scholar CrossRef Search ADS PubMed  10 Frederiksen HW, Zwisler A-D, Johnsen SP, Öztürk B, Lindhardt T, Norredam M. Differences in initiation and discontinuation of preventive medications and use of non- pharmacological interventions after acute coronary syndrome among migrants and Danish born. Eur Heart J  2018; 39:doi:10.1093/eurheartj/ehy227. 11 Freedman B, Lip GYH. ‘Unreal world’ or ‘real world’ data in oral anticoagulant treatment of atrial fibrillation. Thromb Haemost  2016; 116: 587– 589. Google Scholar CrossRef Search ADS PubMed  12 Rivera-Caravaca JM, Roldán V, Esteve-Pastor MA, Valdés M, Vicente V, Lip GYH, Marin F. Cessation of oral anticoagulation is an important risk factor for stroke and mortality in atrial fibrillation patients. Thromb Haemost  2017; 117: 1448– 1454. Google Scholar CrossRef Search ADS PubMed  13 Martinez C, Katholing A, Wallenhorst C, Freedman SB. Therapy persistence in newly diagnosed non-valvular atrial fibrillation treated with warfarin or NOAC. A cohort study. Thromb Haemost  2016; 115: 31– 39. Google Scholar CrossRef Search ADS PubMed  14 Steffel J, Verhamme P, Potpara TS, Albaladejo P, Antz M, Desteghe L, et al.   The 2018 European Heart Rhythm Association Practical Guide on the use of non-vitamin K antagonist oral anticoagulants in patients with atrial fibrillation. Eur Heart J  2018; 39: 1330– 1393. Google Scholar CrossRef Search ADS PubMed  Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2018. For permissions, please email: journals.permissions@oup.com. This article is published and distributed under the terms of the Oxford University Press, Standard Journals Publication Model (https://academic.oup.com/journals/pages/about_us/legal/notices)

Journal

European Heart JournalOxford University Press

Published: Jun 6, 2018

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