Abstract
Background
Coronary heart disease (CHD) is a common and potentially fatal malady with a life time prevalence of over 20%. For Germany, the mortality attributable to chronic ischemic heart disease or acute myocardial infarction is estimated at 140,000 deaths per year. An association between prognosis of CHD and lifestyle risk factors has been consistently shown. To positively influence lifestyle risk factors in patients with CHD, non-pharmaceutical secondary prevention strategies are frequently recommended and implemented.
Objectives
The aim of this HTA (HTA = Health Technology Assessment) is to summarise the current literature on strategies for non-pharmaceutical secondary prevention in patients with CHD and to evaluate their medical effectiveness/efficacy and cost-effectiveness as well as the ethical, social and legal implications. In addition, this report aims to compare the effectiveness and efficacy of different intervention components and to evaluate the generalisability with regard to the German context.
Methods
Relevant publications were identified by means of a structured search of databases accessed through the German Institute of Medical Documentation and Information (DIMDI). In addition, a manual search of identified reference lists was conducted. The present report includes German and English literature published between January 2003 and September 2008 targeting adults with CHD. The methodological quality of included studies was assessed according to pre-defined quality criteria, based on the criteria of evidence based medicine.
Results
Among 9,074 publications 43 medical publications met the inclusion criteria. Overall study quality is satisfactory, but only half the studies report overall mortality or cardiac mortality as an outcome, while the remaining studies report less reliable outcome parameters. The follow-up duration varies between twelve and 120 months. Although overall effectiveness of non-pharmaceutical secondary prevention programs shows considerable heterogeneity, there is evidence for the long-term effectiveness concerning mortality, recurrent cardiac events and quality of life. Interventions based on exercise and also multicomponent interventions report more conclusive evidence for reducing mortality, while interventions focusing on psychosocial risk factors seem to be more effective in improving quality of life. Only two studies from Germany fulfill the methodological criteria and are included in this report.
Additionally, 25 economic publications met the inclusion criteria. Both, quantity and quality of publications dealing with combined interventions are higher compared with those investigating single component interventions. However, there are difficulties in transferring the international results into the German health care system, because of its specific structure of the rehabilitation system. While international literature mostly shows a positive cost-effectiveness ratio of combined programs, almost without exception, studies investigate out-of hospital or home-based programs. The examination of publications evaluating the cost-effectiveness of single interventions merely shows a positive trend of exercise-based and smoking cessation programs. Due to a lack of appropriate studies, no conclusive evidence regarding psychosocial and dietary interventions is available.
Altogether eleven publications concerned with ethical or social issues of non-pharmacological secondary prevention strategies are included. These studies are relatively confirm the assumption that patients with a lower socioeconomic background reflect a population at increased risk and therefore have specific needs to participate in rehabilitation programs. However, there currently remains uncertainty, whether these patients participate in rehabilitation more or less often. As barriers, which deter patients from attending, aspects like a lack of motivation, family commitments or the distance between home and rehabilitation centres are identified. Psychological factors like anxiety, depression and uncertainty as well as physical constraints are also pointed out.
Discussion
Non-pharmacological secondary preventive strategies are safe and effective in improving mortality, morbidity and quality of life in patients with CHD. Because of the small number of reliable studies with long term follow up over 60 months, sustainability of observed intervention effects has to be regarded with caution. Due to a lack of suitable studies, it was not possible to determine the effectiveness of interventions in important patient subgroups as well as the comparative effectiveness of different intervention strategies, conclusively. Future research should, amongst others, attempt to investigate these questions in methodologically rigorous studies.
With regard to the cost-effectiveness of non-pharmacological interventions, overall, international studies show positive results. However, there are considerable limitations due to the qualitative and quantitative deficiencies of identified studies. The special characteristics of the German rehabilitation system with its primarily inpatient offers result in further difficulties, when trying to transfer international study results to the German health care system. Both, studies demonstrating the cost-effectiveness of inpatient programs and those investigating the cost-effectiveness of single interventions are currently not available. To examine the German rehabilitation programs concerning their efficiency and their potential for optimisation, there is a need for further research.
Concerning social and ethical issues, a lack of studies addressing the structure of rehabilitation participants in Germany is striking. The same applies to studies examining the reasons for none participation in non-pharmacological secondary prevention programs. Evidence regarding these questions would provide an informative basis for optimising rehabilitation programs in Germany.
Conclusion
Non-pharmacological secondary prevention interventions are safe and able to reduce mortality from CHD and cardiac events, as well as to imporve patient’s quality of life. Nevertheless, there is considerable need for research; especially the effectiveness of interventions for important subgroups of CHD patients has to be evaluated. In addition to intervention effectiveness, there is also some evidence that interventions generate an appropriate cost-effectiveness ratio. However, future research should investigate this further. The same applies to the sustainability of secondary prevention programs and patient’s reasons for not attending them.
Keywords: Coronary heart disease; secondary prevention; prevention, non-pharmacological; effectiveness; cost-effectiveness; efficiency; intervention, psychosocial; intervention, multimodal; exercise; training; reduction, stress; smoking cessation; dietary change; rehabilitation
Abstract
Hintergrund
Die koronare Herzkrankheit (KHK) ist eine häufige und potenziell tödliche Erkrankung mit einer Lebenszeitprävalenz von über 20%. Allein in Deutschland wird die Zahl der durch die ischämische Herzerkrankung und des akuten Myokardinfarkts jährlich verursachten Todesfälle auf etwa 140.000 geschätzt. Ein Zusammenhang eng mit dem Lebensstil verbundener Risikofaktoren mit Auftreten und Prognose der KHK ist nachgewiesen. Durch Maßnahmen der nichtmedikamentösen Sekundärprävention wird versucht, diese Risikofaktoren positiv zu verändern sowie die KHK im Gegensatz zu palliativen interventionellen Therapiestrategien kausal zu behandeln.
Zur Wirksamkeit der nichtmedikamentösen sekundärpräventiven Maßnahmen liegt eine ganze Reihe von Einzelstudien und -untersuchungen vor, eine systematische Analyse, die die Evidenz aller hauptsächlich angewandten Sekundärpräventionsstrategien zusammenfasst, fehlt unseres Wissens nach bislang jedoch. Auch eine Auswertung vorhandener Studien zur Kosten-Effektivität der Maßnahmen ist hierbei zu integieren.
Fragestellung
Ziel dieses HTA-Berichts (HTA=Health Technology Assessment) ist die Erstellung einer umfassenden Übersicht der aktuellen Literatur zu nichtmedikamentösen Sekundärpräventionsmaßnahmen in der Behandlung der KHK, um diese Maßnahmen und deren Komponenten bezüglich ihrer medizinischen Wirksamkeit sowie Wirtschaftlichkeit zu beurteilen. Weiterhin sollen die ethischen, sozialen und rechtlichen Aspekte der nichtmedikamentösen Sekundärprävention und die Übertragbarkeit der Ergebnisse auf den deutschen Versorgungsalltag untersucht werden.
Methodik
Relevante Publikationen werden über eine strukturierte und hochsensitive Datenbankrecherche sowie mittels Handrecherche identifiziert. Die Literaturrecherche wird in vier Einzelsuchen zu medizinischen, gesundheitsökonomischen, ethischen und juristischen Themen am 18.09.2008 durchgeführt und erstreckt sich über die vergangenen fünf Jahre.
Die methodische Qualität der Publikationen wird von jeweils zwei unabhängigen Gutachtern unter Beachtung von Kriterien der evidenzbasierten Medizin (EbM) systematisch geprüft.
Ergebnisse
Von insgesamt 9.074 Treffern erfüllen 43 medizinische Publikationen die Selektionskriterien, mit einem Nachbeobachtungszeitraum zwischen zwölf und 120 Monaten. Insgesamt ist die Studienqualität zufriedenstellend, allerdings berichtet nur ca. die Hälfte der Studien differenziert die Gesamtmortalität, während die übrigen Studien andere Outcomemaße verwenden. Die Wirksamkeit einzelner Sekundärpräventionsmaßnahmen stellt sich als sehr heterogen dar. Insgesamt kann langfristig eine Reduktion der kardialen sowie der Gesamtmortalität und der Häufigkeit kardialer Ereignisse sowie eine Erhöhung der Lebensqualität beobachtet werden. Vor allem für trainingsbasierte und multimodale Interventionen ist eine effektive Reduktion der Mortalität zu beobachten, während psychosoziale Interventionen besonders in Bezug auf eine Erhöhung der Lebensqualität effektiv zu sein scheinen.
Für die ökonomischen Auswertungen werden 26 Publikationen identifiziert, die von ihrer Themenstellung und Studienart dem hier betrachteten Kontext zugeordnet werden können. Insgesamt kann festgestellt werden, dass sich die Studienlage zur multimodalen Rehabilitation sowohl bezüglich ihrer Menge als auch Qualität der Analysen besser darstellt, als dies für Evaluationen von Einzelmaßnahmen beobachtet werden kann. Die internationale Literatur bestätigt den multimodalen Ansätzen dabei zwar ein gutes Verhältnis von Kosten und Effektivität, untersucht jedoch nahezu ausschließlich ambulante oder häuslichbasierte Maßnahmen. Die Auswertung der Studien, die einzelne sich mit präventiven Maßnahmen in Hinblick auf ihre Kosten-Effektivität beschäftigen, ergibt lediglich positive Tendenzen für Interventionen der Raucherentwöhnung und des körperlichen Trainings. Im Hinblick auf psychosoziale Maßnahmen sowie auch die Ernährungsumstellung können aufgrund der unzureichenden Studienlage jedoch keine Aussagen über die Kosten-Effektivität getroffen werden.
Insgesamt werden im Rahmen der Betrachtung sozialer Aspekte der nichtmedikamentösen Sekundärprävention elf Publikationen einbezogen. Die relativ neuen Studien bestätigen, dass Patienten mit niedrigem sozioökonomischen Status insgesamt schlechtere Ausgangsbedingungen und demnach einen spezifischen Bedarf an rehabilitativer Unterstützung haben. Gleichzeitig sind sich die Forscher jedoch uneinig, ob gerade diese Patientengruppe relativ häufiger oder seltener an den Rehabilitationsmaßnahmen teilnimmt. Bezüglich der Barrieren, die Patienten von der Teilnahme an den präventiven Maßnahmen abhalten, werden psychologische Faktoren, physische Einschränkungen aber auch gesellschaftliche und systemisch-orientierte Einflüsse genannt.
Diskussion
Nichtmedikamentöse Sekundärpräventionsmaßnahmen sind sicher und in der Lage eine Reduktion der Mortalität sowie der Häufigkeit kardialer Ereignisse zu erzielen sowie die Lebensqualität zu erhöhen. Da nur wenige der methodisch verlässlichen Studien Teilnehmer über einen längeren Zeitraum von mindestens 60 Monaten nachverfolgen, müssen Aussagen über die Nachhaltigkeit als limitiert angesehen werden. Verlässliche Angaben in Bezug auf relevante Patientensubgruppen lassen sich nur sehr eingeschränkt machen ebenso wie im Hinblick auf die vergleichende Beurteilung verschiedener Maßnahmen der Sekundärprävention, da diese von eingeschlossenen Studien nur unzureichend erforscht wurden. Zukünftige methodisch verlässliche Studien sind notwendig, um diese Fragestellungen zu untersuchen und zu beantworten.
Bezogen auf die Kosten-Effektivität nichtmedikamentöser sekundärpräventiver Maßnahmen kann aus den internationalen Studien eine insgesamt positive Aussage zusammengefasst werden. Einschränkungen dieser resultieren jedoch zum einen aus den Besonderheiten des deutschen Systems der stationären Rehabilitationsangebote, zum anderen aus den qualitativ mangelhaften Evaluationen der Einzelmaßnahmen. Studien mit dem Ziel der Bewertung der Kosten-Effektivität stationärer Rehabilitationsangebote sind ebenso erforderlich wie auch qualitativ hochwertige Untersuchungen einzeln erbrachter Präventionsmaßnahmen.
Aus sozialer Perspektive sollte insbesondere untersucht werden, welche Patientengruppe aus welchen Gründen von einer Teilnahme an Rehabilitations- bzw. präventiven Maßnahmen absieht und wie diesen Argumenten begegnet werden könnte.
Schlussfolgerung
Nichtmedikamentöse sekundärpräventive Maßnahmen sind in der Lage eine Reduktion der Mortalität und der Häufigkeit kardialer Ereignisse zu erzielen sowie die Lebensqualität zu erhöhen. Eine Stärkung des Stellenwerts nichtmedikamentöser Maßnahmen der Sekundärprävention erscheint vor diesem Hintergrund notwendig. Auch kann für einige Interventionen ein angemessenes Verhältnis von Effektivität und Kosten angenommen werden. Es besteht allerdings nach wie vor erheblicher Forschungsbedarf bezüglich der Wirksamkeitsbeurteilung nichtmedikamentöser Maßnahmen der Sekundärprävention in wichtigen Patientensubgruppen und der Effizienz zahlreicher angebotener Programme. Darüber hinaus ist weitere Forschung notwendig, um die Nachhaltigkeit der Maßnahmen und Gründe für die Nichtinanspruchnahme detailliert zu untersuchen. Vor allem gilt es jedoch den Versorgungsalltag in Deutschland, wie er sich für Ärzte, Patienten und weitere Akteure des Gesundheitswesens darstellt, zu untersuchen und den heutigen Stellenwert nichtmedikamentöser Maßnahmen aufzuzeigen.
Executive Summary
1. Health political background
Coronary heart disease (CHD) is in Germany, as in other industrialised countries an important disease with a substantial burden for individuals and society. Both, mortaltiy statistics and hospital admission diagnoses statistics are dominated by CHD and as a result, disease related costs are substantial.
With this in mind, the relevance of effective prevention programs in the treatment of CHD becomes clear. An effective and cost-effective secondary prevention strategy is essential from a public health perspective.
In addition to drug therapies, non-pharmacological interventions are considered the basis for patients with CHD. These interventions include smoking cessation, exercise training, dietary programs or psychosocial interventions. In Germany they are offered as single or combined methods within rehabilitaion clinics or in so called “heart groups”.
A great number of studies and research is available, investigating the effectiveness of non-pharmacological interventions, but a systematic analysis, at least from a German perspective, is currently lacking, as are evaluations of their cost-effectiveness.
The present HTA (HTA=Health Technology Assessment) therefore aims to summarise current literature on non-pharmacologicall secondary prevention of CHD and to evaluate their effectiveness and efficiency. Areas with insufficient evidence should also be identified in order to guide future research.
2. Scientific background
CHD is a common and potentially fatal disease with a lifetime prevalence of 20%. Cardiovascular diseases (CVD) are responsible for most of the deaths in developing as well as in developed countries. In Germany 43% of all deaths were attributable to CVD in 2006. Development of CHD is multicausal and related to many cardiovascular lifestyle risk factors. Many relevant risk factors have been identified, which are potentially modifiable. In the German Monica-Augsburg study it has been shown, that 65% of the myocardial infarctions can be attributed to smoking, hypertension and high blood lipids. In this context, interventions to change harmful lifestyle behaviour play an important role in the treatment of patients with CHD.
3. Research questions
The aim of this HTA is to summarise current literature on secondary prevention interventions in patients with CHD and to evaluate their medical effectiveness/efficacy and cost-effectiveness as well as the ethical, social and legal implications of secondary prevention programs. In order to do so, the following research questions will be addressed from a medical standpoint:
What is the effectiveness of combined non-pharmaceutical secondary prevention interventions in the treatment of CHD?
What is the effectiveness of single non-pharmaceutical secondary prevention interventions in the treatment of CHD?
What is the effectiveness of combined/single non-pharmaceutical secondary prevention interventions in the treatment of CHD compared to each other?
What is the effectiveness of combined and single non-pharmaceutical secondary prevention interventions related to specific subgroups of patients, such as men or women, patients with stable CHD, acute myocardial infarction, or following revascularization, patients with comorbid conditions, or socially deprived patients etc.?
What is the effectiveness of combined/single non-pharmaceutical secondary prevention programs in comparison or in addition to alternative therapy options in the treatment of CHD?
How safe are combined/single non-pharmaceutical secondary prevention interventions in the treatment of CHD?
Considering that financial resources are limited, it is necessary to relate the benefits of non-pharmaceutical secondary prevention strategies to its costs and to compare the results with alternative options. Therefore the following questions result from an economic dimension:
To what extent can non-pharmacological secondary prevention strategies be classified as efficient?
How efficient are combined interventions? How efficient are single component interventions?
Concerning social and ethical aspects, the following questions should be answered:
What are the reasons for patients not to participate in available non-pharmacological interventions?
Could specific interventions help to overcome underutilisation and distortions of demand?
4. Methods
Relevant publications were identified by means of a structured search of databases accessed through the German Institute of Medical Documentation and Information (DIMDI). In addition a manual search of identified reference lists was conducted. The former included the following electronic resources:
DAHTA; INAHTA (NHS-CRD-HTA); NHSEED; CDAR94 (NHS-CRD-DARE); CDSR93 (Cochrane Library); ME00 (MEDLINE); EM00 (EMBASE); CB85 (AMED); BA90 (BIOSIS Previews); MK77 (MEDIKAT); CCTR93 (Cochrane Library – Central); GA03 (gms); SM 78 (SOMED); CV72 (CAB Abstracts); II78 (ISTPB + ISSHP); ED93 (ETHMED); AZ72 (GLOBAL Health); AR 96 (Deutsches Ärzteblatt); ME0A (Medline Alert); EA08 (Embase Alert); IS90 (SciSearch); CC00 (CCMed); IN73 (Social SciSearch); KR03 (Karger Publisher Database); KL97 (Kluwer Publisher Database); SP97 (Springer Publisher Database); SPPP (Springer Publisher Database PrePrint); TV01 (Thieme Publisher Database).
The present report includes German and English literature published between January 2003 and September 2008. The search parameters can be found in the appendix. The target population was adults with CHD. The methodological quality of included studies was assessed using standardised checklists and rated according to criteria recommended by the “Scottish Intercollegiate Guidelines Network Grading Review Group“ (SIGN).
5. Results
5.1 Medical results
Among 4,798 publications, the selection process identifies 43 publications reporting the results of 27 primary studies and eight meta-analyses meeting the pre-specified inclusion criteria. These include 24 studies rated with good and high methodological quality. Multimodal secondary prevention programs are investigated in 14 studies, eleven studies investigate exercise based secondary prevention interventions, seven programs focus on psychosocial interventions while diet and smoking cessation interventions are each investigated in three studies. Among 35 included medical publications, only 18 report amongst others mortality as an outcome parameter, while the remaining studies report alternative outcomes. Duration of follow-up varies between twelve and 120 months. Although overall effectiveness of prevention programs shows considerable heterogeneity, there is evidence for the effectiveness of non-pharmaceutical secondary prevention interventions. Especially programs including exercise interventions report reductions in mortality, while psychosocial programs seem to improve quality of life in particular. Only a few of the included studies have a follow up with a duration of more than 60 months. Only two studies from Germany fulfill the methodological requirements and are included in this report.
5.2 Health economic results
Out of 3,789 publications, 25 economic studies met the inclusion criteria.
Seven of these publications are cost-utility-analyses, seven are cost-effectiveness-analyses, another three are reviews, three can be classified as “expert opinion”, two as “guidelines” and one is a comparative cost-analysis. Two health technology assessments are also included.
In summary, both quantity and quality of publications examining combined interventions are higher compared with those investigating single interventions. However, there are difficulties in transferring the international results into the German health care system, because of its specific structure of the rehabilitation system. While international literature mostly shows a positive cost-effectiveness ratio of combined programs, almost without exception, studies investigate out-of hospital or home-based programs. The examination of publications evaluating the cost-effectiveness of single interventions merely shows a positive trend of exercise-based and smoking cessation programs. Due to a lack of appropriate studies, no conclusive evidence regarding psychosocial and dietary interventions is available.
5.3 Social results
Altogether eleven publications concerned with ethical or social issues of non-pharmacological secondary prevention strategies are included. These publications are either based on surveys, data analyses or expert opinions. Studies confirm the assumption that patients with a lower socioeconomic background reflect a population at increased risk and therefore have specific needs to participate in rehabilitation programs. However, there currently remains uncertainty, whether these patients participate in rehabilitation more or less often. As barriers, which deter patients from attending, aspects like a lack of motivation, family commitments or the distance between home and rehabilitation centres are identified. Psychological factors like anxiety, depression and uncertainty as well as physical constraints are also pointed out.
6. Discussion
6.1 Discussion of medical aspects
Non-pharmacological secondary prevention interventions in the treatment of CHD are effective to improve mortality, morbidity and quality of life. While there is considerable heterogeneity in study quality, follow-up duration and reported effect sizes, the overall quality of included studies is satisfactory. Because follow up duration is predominantly twelve to 24 months, conclusions about the sustainability of the interventions are limited. With regard to mortality exercise based interventions provided most conclusive evidence for effectiveness while psychosocial interventions particularly seem to improve quality of life effectively. Due the limited number of studies investigating diet or smoking cessation, reliable conclusions regarding the effectiveness of those components are limited. Although only two studies from Germany are included, the majority of studies are from industrialised countries and there is no evidence, that these findings are not applicable to the German context.
6.2 Discussion of economic aspects
With regard to the cost-effectiveness of non-pharmaceutical interventions, overall, international studies show positive results. However, there are considerable limitations due to the qualitative and quantitative deficiencies of identified studies. The special characteristics of the German rehabilitation system with its primarily inpatient offers result in further difficulties, when trying to transfer international study results to the German health care system. Both, studies demonstrating the cost-effectiveness of inpatient programs and those investigating the cost-effectiveness of single interventions are currently not available. To examine the German rehabilitation programs concerning their efficiency and their potential for optimisation, there is a need for further research.
6.3 Discussion of social aspects
Concerning social and ethical issues, a lack of studies addressing the structure of rehabilitation participants in Germany is striking. The same applies to studies examining the reasons for none participation in non-pharmaceutical secondary prevention programs. Evidence regarding these questions would provide an informative basis for optimising rehabilitation programs in Germany.
7. Conclusion/Recommendations
Non-pharmacological secondary prevention programs in patients with CHD can be effective in the improvement of mortality, morbidity and quality of life. Especially multimodal programs and those including exercise based strategies seem advisable. Considering transferability to the German context, presented findings at present have to be considered best available evidence for the development of secondary prevention programs in Germany, as long as methodologically reliable studies of current prevention programs are unavailable.
Future research should aim to investigate the effectiveness of secondary prevention programs in specific subgroups of patients, such as women, patients with comorbidities, and socially deprived patients. Furthermore, the comparative effectiveness of different secondary prevention strategies needs to be investigated. In addition, factors should be identified, which can improve implementation and adoption of secondary prevention programs in everyday care.
There is on the one hand a lack of cost-effectiveness analyses of hospital based or inpatient rehabilitation programs, and on the other hand positive results of out of hospital or home-based interventions. This should facilitate the evaluation of non-pharmacoloogical secondary prevention programs specific to the German health care system and provide better evidence regarding their efficiency and potential for optimisation. Effectiveness and cost-effectiveness should further be investigated for different patient subgroup. Concerning the evaluation of single component interventions, further research is also warranted.
While there is conclusive evidence that patients of lower socio-economic status are at increased overall risk in Germany and therefore have a special need for rehabilitation interventions, there remains uncertainty, whether these patients participate in rehabilitation more or less often. As barriers, which deter patients from attending, aspects like a lack of motivation, family commitments or the distance between home and rehabilitation centres are identified. These factors should be examined with a specific focus on the German health care system, in order to improve future non-pharmacological secondary prevention programs.