Acute Coronary Syndrome in Croatia

    Authors

    Abstract

    In the field of acute coronary syndrome management by the methods of interventional cardiology (percutaneous coronary intervention, PCI), Croatian medicine has closely followed international results in spite of the relatively low investments in the Croatian healthcare system as compared with industrialized countries. Since the establishment of the Croatian Primary Percutaneous Coronary Intervention Network, i.e. in the last decade, more than 15,000 patients with acute myocardial infarction with ST-segment elevation (STEMI) were treated with PCI; the same treatment protocol has also been applied in other patients with unstable acute coronary syndrome. In recent years, the network has managed 540-550 patients with acute STEMI per million inhabitants, with each of the eleven PCI centers providing care for more than 384,000 catchment population through 24/7 work schedule. The trends observed in the past decade show the risk profile of these patients to increase, while maintaining the results of treatment at the levels comparable to those reported from similar PCI networks (postprocedural TIMI III flow up to 91% and in-hospital mortality ranging from 4.4% to 6.3%). Future plans include development of a continuous prospective electronic Registry of Invasive and Interventional Cardiology and Acute Coronary Syndrome, further reduction of reperfusion time, increasing introduction of optimal medication and materials in the treatment of these patients, and optimization of treatment of acute myocardial infarction without ST-segment elevation all over Croatia.

    Keywords

    acute coronary syndrome, interventional cardiology, Croatia

    DOI

    https://doi.org/10.15836/ccar2016.307

    Full Text

    ## Introduction There are few fields in medicine that have made such a breakthrough as the management of acute coronary syndrome in the past fifteen years. Development of modern interventional cardiology during the 2000s has reduced in-hospital mortality in acute myocardial infarction to around 5%. Because of the complex establishment and organization of the percutaneous coronary intervention (PCI) service at healthcare institutions, especially based on 24/7 work schedule, current methods of treatment were at the beginning available only to a limited number of patients, i.e. those living or happening to be in the vicinity of a PCI center. In the first decade of this century, the concept of emergency transportation of patients with acute coronary syndrome to PCI centers, in particular high-volume ones, emerged and was scientifically verified, followed by the lively period of organizing primary PCI networks, at first in European countries and then also elsewhere ( 1 - 5 ). These efforts have dramatically increased the number of optimally managed patients with acute coronary syndrome, thus also upgrading the quality of healthcare in general. Then, the so-called fast-track protocols have been launched, avoiding nearby general hospitals and transporting patients directly to PCI centers, emphasizing the importance of the earliest possible 12-lead electrocardiogram (ECG) analysis (within ten minutes of the first medical contact), suggesting various methods to reduce the door-to-balloon time, and launching public health actions to reduce the pain-to-door time. In addition, development and improvement of the materials used in interventional cardiology have been carefully monitored, along with efforts invested to elucidate some unknowns from the beginnings of interventional therapy (e.g., thrombaspiration, the role of GPIIb/IIIa, advantages of transradial approach, etc.). Pharmacotherapy of acute coronary syndrome has also been through quite a tumultuous period, with ever broader and more efficient array of drugs used in antiaggregation therapy ( 6 - 13 ). ## Treatment of Acute Coronary Syndrome in Croatia In the field of acute coronary syndrome management by the methods of interventional cardiology, Croatia has very closely followed international results as one of only few fields in modern medicine. It should be noted that gross domestic product (GDP) in Croatia in 2013 was around 13,500 USD, ranking it among the poorest European Union countries, with 7.3% GDP public health allocations. In spite of these facts as compared with developed countries, Croatia succeeded to keep pace with the world trends and had a number of PCI centers initiating 24/7 work schedule established as early as the mid-2000s. The idea of developing a PCI network in order to enhance primary PCI availability, in particular taking into account the Croatian geographical specificities, was building up in the first years of this millennium. Upon appointment of the Task Force for Acute Coronary Syndrome of the Croatian Society of Cardiology in 2004 and launching the project of PCI center network to ensure urgent management of acute coronary syndrome by the methods of interventional cardiology all over Croatia and its acceptance by the Ministry of Health of the Republic of Croatia, due preconditions were met for the primary PCI network to start working in 2005. The main goal of establishing the primary PCI network was to provide equal levels of treatment for acute myocardial infarction to all inhabitants of Croatia, while the basic principles of its development were gradual network implementation in the national healthcare system, even development of PCI centers in all parts of Croatia, and continuous communication among the network members at all healthcare levels. Nowadays, the primary PCI network has been deeply rooted in Croatian healthcare system, functioning through collaboration among regional PCI centers, catchment county hospitals and general hospitals, and emergency medicine service ( 14 , 15 ). In the past ten years of the Croatian Primary PCI Network existence ( Figure 1 ), more than 15,000 patients with acute myocardial infarction with ST-segment elevation (STEMI) underwent urgent treatment using the methods of interventional cardiology, and other patients with unstable acute coronary syndrome being also managed by the same treatment protocol. In recent years, the network has managed 540-550 patients with acute STEMI per million inhabitants ( Figure 2 ), approaching the optimal figure of at least 600 primary PCIs per million inhabitants, ranking Croatia side by side with the most developed countries in Europe and the world. In European countries, one PCI center has a catchment population of 31,300-6,533,000 on average, whereas each of the eleven PCI centers in Croatia with 24/7 work schedule has a catchment population of 384,000 inhabitants, which is within the optimal limits. According to records on the past ten years, there is an overt increase in the risk profile of patients treated for acute STEMI in the Croatian Primary PCI Network, as follows: patient age (from 60 years in the beginning to 63 years in recent years); female sex (from 27% to 31%); prevalence of patients presenting with cardiogenic shock (from 6.7% to 7.6%); and other (involvement of the left ventricular anterior wall, left coronary artery trunk, bypasses, etc.). In spite of the above mentioned increase in the patient risk profile, number of patients treated in acute STEMI and a number of new centers having joined the Primary PCI Network, the proportion of optimal TIMI III flow achieved at the end of the procedure has increased with time (from 87% to 91%), with the mortality rate ranging from 4.4% to 6.3%. These results certainly are one of the major reasons for a decreasing trend recorded in the mortality from coronary heart disease, as well as in the overall cardiovascular mortality in Croatia in the past ten years ( Figure 3 ). The results reported above are comparable with those from similar primary PCI networks at the regional and national levels in countries with a substantially higher GDP and greater healthcare investments. That is why the Croatian Primary PCI Network has been recognized in relevant cardiologic settings, and its results have been published in renowned scientific and professional medical periodicals ( 16 - 21 ). Croatian Primary Percutaneous Coronary Intervention Network. Number of patients with acute ST-elevation myocardial infarction treated with primary percutaneous coronary intervention per million inhabitants of Croatia. Cardiovascular mortality in Croatia. ## Future Plans Retrospective data collection on the Croatian results achieved with interventional management of acute myocardial infarction, STEMI in particular, performed biannually by the Working Group for Acute Coronary Syndrome of the Croatian Society of Cardiology, corresponds to retrospective discontinuous registries usually established as an interim solution in the process of developing optimal continuous prospective registries. Such registries facilitate data accessibility and monitoring trends related to diseases and other associated events, also applicable to acute coronary syndrome ( 22 - 24 ). Since 2015, the Working Group for Acute Coronary Syndrome and Working Group for Interventional Cardiology of the Croatian Society of Cardiology in collaboration with the Agency for Quality and Accreditation in Healthcare and Social Welfare work on the development of a continuous prospective Registry of Invasive and Interventional Cardiology and Acute Coronary Syndrome. Data on patients treated by the methods of interventional cardiology in PCI centers all over Croatia, including those treated with the diagnosis of acute coronary syndrome, will be entered electronically in the Registry. The preliminary organizational activities and aims of the Registry have already been presented at conferences of the Croatian invasive and interventional cardiologists. Full implementation of the Registry is expected by the end of 2016. The Registry will provide a series of data on the management of acute coronary syndrome in Croatia, however, a number of data will not be included (e.g., percentage of fibrinolysis treated or non-reperfusion patients with acute STEMI, therapy and results of treatment in patients with acute coronary syndrome not treated with the methods of invasive and interventional cardiology, etc.). Such data will only be provided by the Registry of Acute Coronary Syndrome designed for a defined long-term purpose, which will also include all other Croatian hospitals along with PCI centers. According to data from the current Registry, the number of myocardial infarction without ST-segment elevation cases treated by the methods of interventional cardiology within the first hours to days after coronary event is lower in comparison with STEMI cases. This in particular holds for hospitals where such treatment is not available, thus undoubtedly influencing the morbidity and mortality of these patients. This situation is generally caused by financial difficulties, calling for appropriate activities to change it in the near future. In addition, there is also room for improvement in the organization of patient transport within the network. For example, the fast-track system generally does not work, with the exception of the Istria County and Krapina-Zagorje County, so that patients in the acute stage of myocardial infarction waste precious time for driving to the hospitals where interventional treatment is not available. In most cases, 12-lead ECG analysis is not available at the initial medical contact, i.e. in the ambulance or general medicine office, thus also wasting time to make the diagnosis and initiate treatment for this frequently life threatening condition. In an attempt to correct such illogical situations, the Working Group of Acute Coronary Syndrome takes active part in continuous education on this issue, intended for the physicians engaged in the network in all parts of Croatia. In 2015-2016, a simple graphic Algorithm for Diagnosis and Treatment of Acute Myocardial Infarction has been designed ( Figure 4 ) and distributed to healthcare institutions all over Croatia. Algorithm for Diagnosis and Treatment of Acute Myocardial Infarction. In the last year, great breakthrough has been made in the availability of current antithrombotic therapy in Croatia. As it is known, prasugrel and ticagrelor currently are the antiplatelet drugs of choice in the treatment of acute myocardial infarction ( 8 - 11 ). While the former has not been registered in Croatia, since 2015 ticagrelor is available without payment to STEMI patients treated with PCI for the first six months postoperatively, thus having increased its penetration in STEMI in Croatia from 52% in the first half of 2015 to 79% in the first half of 2016. These data on the third-generation antiplatelet drug in STEMI are comparable to those reported from the most industrialized European countries. However, as after six months, ticagrelor is not available without copayment to STEMI patients and all patients with acute coronary syndrome without ST-segment elevation, its penetration is very low in these diagnoses, thus additional efforts should be invested to change this unfavorable situation. Although there are no precise data for now, penetration of the drug eluting stents at the national level has been estimated to around 40%, also requiring steps for improvement. ## Conclusion Considering all the facts mentioned above, there certainly is room for upgrading at all levels of acute coronary syndrome management, in spite of the very good results achieved in the management of STEMI in Croatia, which considerably surpass the Croatian healthcare average. These superior results can be additionally improved by continuing enthusiastic and dedicated work of all health professionals involved in the treatment of this serious condition, but also by further investments in the infrastructure, materials, drugs, education and human resources.

    Cardiologia Croatica
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    Acute Coronary Syndrome in Croatia

    Review Article
    Issue8
    Published
    Pages307-313
    PDF via DOIhttps://doi.org/10.15836/ccar2016.307
    acute coronary syndrome
    interventional cardiology
    Croatia

    Authors

    Zdravko Babić*ORCIDCroatia
    Marin PavlovORCIDCroatia

    Abstract

    In the field of acute coronary syndrome management by the methods of interventional cardiology (percutaneous coronary intervention, PCI), Croatian medicine has closely followed international results in spite of the relatively low investments in the Croatian healthcare system as compared with industrialized countries. Since the establishment of the Croatian Primary Percutaneous Coronary Intervention Network, i.e. in the last decade, more than 15,000 patients with acute myocardial infarction with ST-segment elevation (STEMI) were treated with PCI; the same treatment protocol has also been applied in other patients with unstable acute coronary syndrome. In recent years, the network has managed 540-550 patients with acute STEMI per million inhabitants, with each of the eleven PCI centers providing care for more than 384,000 catchment population through 24/7 work schedule. The trends observed in the past decade show the risk profile of these patients to increase, while maintaining the results of treatment at the levels comparable to those reported from similar PCI networks (postprocedural TIMI III flow up to 91% and in-hospital mortality ranging from 4.4% to 6.3%). Future plans include development of a continuous prospective electronic Registry of Invasive and Interventional Cardiology and Acute Coronary Syndrome, further reduction of reperfusion time, increasing introduction of optimal medication and materials in the treatment of these patients, and optimization of treatment of acute myocardial infarction without ST-segment elevation all over Croatia.

    Full Text

    ## Introduction There are few fields in medicine that have made such a breakthrough as the management of acute coronary syndrome in the past fifteen years. Development of modern interventional cardiology during the 2000s has reduced in-hospital mortality in acute myocardial infarction to around 5%. Because of the complex establishment and organization of the percutaneous coronary intervention (PCI) service at healthcare institutions, especially based on 24/7 work schedule, current methods of treatment were at the beginning available only to a limited number of patients, i.e. those living or happening to be in the vicinity of a PCI center. In the first decade of this century, the concept of emergency transportation of patients with acute coronary syndrome to PCI centers, in particular high-volume ones, emerged and was scientifically verified, followed by the lively period of organizing primary PCI networks, at first in European countries and then also elsewhere ( 1 - 5 ). These efforts have dramatically increased the number of optimally managed patients with acute coronary syndrome, thus also upgrading the quality of healthcare in general. Then, the so-called fast-track protocols have been launched, avoiding nearby general hospitals and transporting patients directly to PCI centers, emphasizing the importance of the earliest possible 12-lead electrocardiogram (ECG) analysis (within ten minutes of the first medical contact), suggesting various methods to reduce the door-to-balloon time, and launching public health actions to reduce the pain-to-door time. In addition, development and improvement of the materials used in interventional cardiology have been carefully monitored, along with efforts invested to elucidate some unknowns from the beginnings of interventional therapy (e.g., thrombaspiration, the role of GPIIb/IIIa, advantages of transradial approach, etc.). Pharmacotherapy of acute coronary syndrome has also been through quite a tumultuous period, with ever broader and more efficient array of drugs used in antiaggregation therapy ( 6 - 13 ). ## Treatment of Acute Coronary Syndrome in Croatia In the field of acute coronary syndrome management by the methods of interventional cardiology, Croatia has very closely followed international results as one of only few fields in modern medicine. It should be noted that gross domestic product (GDP) in Croatia in 2013 was around 13,500 USD, ranking it among the poorest European Union countries, with 7.3% GDP public health allocations. In spite of these facts as compared with developed countries, Croatia succeeded to keep pace with the world trends and had a number of PCI centers initiating 24/7 work schedule established as early as the mid-2000s. The idea of developing a PCI network in order to enhance primary PCI availability, in particular taking into account the Croatian geographical specificities, was building up in the first years of this millennium. Upon appointment of the Task Force for Acute Coronary Syndrome of the Croatian Society of Cardiology in 2004 and launching the project of PCI center network to ensure urgent management of acute coronary syndrome by the methods of interventional cardiology all over Croatia and its acceptance by the Ministry of Health of the Republic of Croatia, due preconditions were met for the primary PCI network to start working in 2005. The main goal of establishing the primary PCI network was to provide equal levels of treatment for acute myocardial infarction to all inhabitants of Croatia, while the basic principles of its development were gradual network implementation in the national healthcare system, even development of PCI centers in all parts of Croatia, and continuous communication among the network members at all healthcare levels. Nowadays, the primary PCI network has been deeply rooted in Croatian healthcare system, functioning through collaboration among regional PCI centers, catchment county hospitals and general hospitals, and emergency medicine service ( 14 , 15 ). In the past ten years of the Croatian Primary PCI Network existence ( Figure 1 ), more than 15,000 patients with acute myocardial infarction with ST-segment elevation (STEMI) underwent urgent treatment using the methods of interventional cardiology, and other patients with unstable acute coronary syndrome being also managed by the same treatment protocol. In recent years, the network has managed 540-550 patients with acute STEMI per million inhabitants ( Figure 2 ), approaching the optimal figure of at least 600 primary PCIs per million inhabitants, ranking Croatia side by side with the most developed countries in Europe and the world. In European countries, one PCI center has a catchment population of 31,300-6,533,000 on average, whereas each of the eleven PCI centers in Croatia with 24/7 work schedule has a catchment population of 384,000 inhabitants, which is within the optimal limits. According to records on the past ten years, there is an overt increase in the risk profile of patients treated for acute STEMI in the Croatian Primary PCI Network, as follows: patient age (from 60 years in the beginning to 63 years in recent years); female sex (from 27% to 31%); prevalence of patients presenting with cardiogenic shock (from 6.7% to 7.6%); and other (involvement of the left ventricular anterior wall, left coronary artery trunk, bypasses, etc.). In spite of the above mentioned increase in the patient risk profile, number of patients treated in acute STEMI and a number of new centers having joined the Primary PCI Network, the proportion of optimal TIMI III flow achieved at the end of the procedure has increased with time (from 87% to 91%), with the mortality rate ranging from 4.4% to 6.3%. These results certainly are one of the major reasons for a decreasing trend recorded in the mortality from coronary heart disease, as well as in the overall cardiovascular mortality in Croatia in the past ten years ( Figure 3 ). The results reported above are comparable with those from similar primary PCI networks at the regional and national levels in countries with a substantially higher GDP and greater healthcare investments. That is why the Croatian Primary PCI Network has been recognized in relevant cardiologic settings, and its results have been published in renowned scientific and professional medical periodicals ( 16 - 21 ). Croatian Primary Percutaneous Coronary Intervention Network. Number of patients with acute ST-elevation myocardial infarction treated with primary percutaneous coronary intervention per million inhabitants of Croatia. Cardiovascular mortality in Croatia. ## Future Plans Retrospective data collection on the Croatian results achieved with interventional management of acute myocardial infarction, STEMI in particular, performed biannually by the Working Group for Acute Coronary Syndrome of the Croatian Society of Cardiology, corresponds to retrospective discontinuous registries usually established as an interim solution in the process of developing optimal continuous prospective registries. Such registries facilitate data accessibility and monitoring trends related to diseases and other associated events, also applicable to acute coronary syndrome ( 22 - 24 ). Since 2015, the Working Group for Acute Coronary Syndrome and Working Group for Interventional Cardiology of the Croatian Society of Cardiology in collaboration with the Agency for Quality and Accreditation in Healthcare and Social Welfare work on the development of a continuous prospective Registry of Invasive and Interventional Cardiology and Acute Coronary Syndrome. Data on patients treated by the methods of interventional cardiology in PCI centers all over Croatia, including those treated with the diagnosis of acute coronary syndrome, will be entered electronically in the Registry. The preliminary organizational activities and aims of the Registry have already been presented at conferences of the Croatian invasive and interventional cardiologists. Full implementation of the Registry is expected by the end of 2016. The Registry will provide a series of data on the management of acute coronary syndrome in Croatia, however, a number of data will not be included (e.g., percentage of fibrinolysis treated or non-reperfusion patients with acute STEMI, therapy and results of treatment in patients with acute coronary syndrome not treated with the methods of invasive and interventional cardiology, etc.). Such data will only be provided by the Registry of Acute Coronary Syndrome designed for a defined long-term purpose, which will also include all other Croatian hospitals along with PCI centers. According to data from the current Registry, the number of myocardial infarction without ST-segment elevation cases treated by the methods of interventional cardiology within the first hours to days after coronary event is lower in comparison with STEMI cases. This in particular holds for hospitals where such treatment is not available, thus undoubtedly influencing the morbidity and mortality of these patients. This situation is generally caused by financial difficulties, calling for appropriate activities to change it in the near future. In addition, there is also room for improvement in the organization of patient transport within the network. For example, the fast-track system generally does not work, with the exception of the Istria County and Krapina-Zagorje County, so that patients in the acute stage of myocardial infarction waste precious time for driving to the hospitals where interventional treatment is not available. In most cases, 12-lead ECG analysis is not available at the initial medical contact, i.e. in the ambulance or general medicine office, thus also wasting time to make the diagnosis and initiate treatment for this frequently life threatening condition. In an attempt to correct such illogical situations, the Working Group of Acute Coronary Syndrome takes active part in continuous education on this issue, intended for the physicians engaged in the network in all parts of Croatia. In 2015-2016, a simple graphic Algorithm for Diagnosis and Treatment of Acute Myocardial Infarction has been designed ( Figure 4 ) and distributed to healthcare institutions all over Croatia. Algorithm for Diagnosis and Treatment of Acute Myocardial Infarction. In the last year, great breakthrough has been made in the availability of current antithrombotic therapy in Croatia. As it is known, prasugrel and ticagrelor currently are the antiplatelet drugs of choice in the treatment of acute myocardial infarction ( 8 - 11 ). While the former has not been registered in Croatia, since 2015 ticagrelor is available without payment to STEMI patients treated with PCI for the first six months postoperatively, thus having increased its penetration in STEMI in Croatia from 52% in the first half of 2015 to 79% in the first half of 2016. These data on the third-generation antiplatelet drug in STEMI are comparable to those reported from the most industrialized European countries. However, as after six months, ticagrelor is not available without copayment to STEMI patients and all patients with acute coronary syndrome without ST-segment elevation, its penetration is very low in these diagnoses, thus additional efforts should be invested to change this unfavorable situation. Although there are no precise data for now, penetration of the drug eluting stents at the national level has been estimated to around 40%, also requiring steps for improvement. ## Conclusion Considering all the facts mentioned above, there certainly is room for upgrading at all levels of acute coronary syndrome management, in spite of the very good results achieved in the management of STEMI in Croatia, which considerably surpass the Croatian healthcare average. These superior results can be additionally improved by continuing enthusiastic and dedicated work of all health professionals involved in the treatment of this serious condition, but also by further investments in the infrastructure, materials, drugs, education and human resources.