FACULTY OF MEDICINE UNIVERSITY OF PORTO Department of Biostatistics and Medical Informatics Introduction to Medicine 2005/2006 Ambulatory monitoring for heart failure patient: comparison between home monitoring and usual care or daily clinics and usual care Barros J (med05219@med.up.pt), Barros JM (med05218@med.up.pt), Coutinho S (med05097@med.up.pt), Fernandes C (med05174@med.up.pt), Ferreira Mª (med05025@med.up.pt), Gomes J (med05239@med.up.pt), Lima J (med05216@med.up.pt), Neves J (med05221@med.up.pt), Puga F (med05242@med.up.pt), Rocha J (med05215@med.up.pt), Silva J (med05217@med.up.pt) 2006 Head teacher: Prof. Dr. Altamiro da Costa Pereira Guiding teacher: Dr. Filipa Almeida (filipa.almeida@med.up.pt) Abstract Introduction: Heart failure (HF) afflicts several people all over the world so it extremely important to improve treatment management strategies. Heart failure patients can be supervised by an ambulatory system in alternative to the standard care. Aim: Comparison between home monitoring and usual care or daily clinics and usual care, in order to find out if there are additional advantages in these two types of ambulatory monitoring in comparison with usual care. Methods: A literature search was performed including randomized clinical trials using the databases MEDLINE and Cochrane library, from the earliest article available until the March 2006. Results: In relation to mortality, home monitoring comparing with the standard care revealed a RR (relative risk) reduction for the home treatment of 38% (RR 0,62 [IC95% 0,46;0,84]). With the study of the association between daily clinics and usual care as far as mortality was concerned RR reduction for daily clinics of 45% was obtained (RR 0,55 [IC95% 0,41;0,75]). These results were statistically significant. Concerning the readmissions the comparison between home monitoring and standard care revealed a RR of 0, 81 (IC95% 0,34;1,96). The results were not statistically significant. The comparison between daily clinics and usual care concerning the readmission rate, demonstrate a RR reduction in readmission for daily clinics patients of 33% (RR 0,67 [IC95% 0,56;0,81])for those which the follow up time was less than one year. The results for the patients followed up for one year or more didn t have statistically significant results. Conclusion: A statistical significant reduction was found in mortality in the group of patients submitted to home monitoring or daily clinics monitoring when compared to standard care. Concerning the hospital readmission rate, there was a significant reduction in the intervention group submitted to daily clinics monitoring when the follow up was less than a year. No statistical difference was found in patients submitted to daily clinics monitoring followed for more than a year or for patients submitted to home monitoring. Studies comparing daily clinics with home monitoring are needed to establish what is the best home treatment for chronic heart failure patients. Keywords: Chronic heart failure; Home monitoring; Telemonitoring; Outpatient management, Heart failure clinics 1
Introduction Heart failure (HF) afflicts several people all over the world so it extremely important to improve treatment management strategies. Heart or cardiac failure (HF) is the pathophysiologic state in which the heart is enable to pump blood at a rate commensurate with the requirements of the metabolizing tissues [1]. It s a complex clinical syndrome that can result from any structural or functional cardiac disorders that impairs the ability of the ventricle to fill with or eject blood [2]. Although this is a very restricted concept as there are plenty definitions and none reveals completely its multidynamic character and only selective features of this complex syndrome are highlighted. None is entirely satisfactory [3]. This pathology may result of an aggravation of other diseases or conditions that interfere with the well functioning of cardiac muscle. The effective symptoms and signs, like breathlessness, fatigue and ankle swelling, seem to be common to other diseases making the clinical diagnosis difficult, especially in women, elderly and obese. The most common aetiologies are the coronary artery disease, high blood pressure (hypertension), valve abnormalities, cardiomyopathy (heart muscle disease- Dilated/ Hypertrophic/ Restrictive), rhythm disturbances and idiopathic [4]. Concerning the prevalence and incidence, previous studies concluded that 4,9 million persons in USA are being treated for heart failure [5] and 10% of patients older than 75 years have heart failure. Actually, this pathology is the most common cause of hospitalization due to cardiovascular disease in patients over 65 years of age [6]. The number of HF deaths has increased steadily despite advances in treatment [7] as a consequence of the extraordinary number of new cases diagnosed each year (550.000 [6]). Thus, the aim of the HF treatment is to control the disease s progression, decreasing the worsening of symptoms, with the crucial purpose of improving patients quality of life and to avoid re-admissions, as its most common forms cannot be completely eliminated. The prevention of heart failure should always be a primary objective [8]. There are a lot of drugs that can be used in the treatment of HF, such as: pharmacological therapy like ACE- inhibitors, diuretics, beta- adrenoceptor antagonists, vasodilator agents and positive inotropic agents and also non-pharmacological management, devices and surgery [3]. As a result, monitoring allows the control of variables (blood pressure, pulse and oximetry) measured by patients at home or in a health care system. Ambulatory 2
monitoring can provide diagnostic information which is then interpreted by expertise in order to assist treatment decisions. Most patients have multiple medical, social and behavioural challenges, and effective care requires a multidisciplinary system [9]. So, there are a lot of HF diseasemanagement programs to provide Intensive patient education, try to encourage patients to be more aggressive in their care, to keep them in a close supervision (close monitoring), to carefully review the medication and others. So, we proposed ourselves to perform a systematic review based in clinical trials with the objective to establish the comparison between home monitoring and usual care or daily clinics and usual care, in order to find out if there are additional advantages in these two types of ambulatory monitoring in comparison with usual care. Methods I. Bibliographic research A systematic review including randomized clinical trials was made using the databases MEDLINE and Cochrane library, from the earliest article available until the March 2006. Two queries were used: Pubmed s query ("Heart Failure, Congestive"[MeSH] OR "chronic heart failure" OR "heart insufficiency" OR "cardiac insufficiency" OR cardiac failure AND "Monitoring, Ambulatory"[MeSH] OR "home monitoring" OR "self monitoring" OR Telemedicine"[MeSH] OR telemonitoring OR home care OR outpatient management OR heart failure clinics OR "Outpatient Clinics, Hospital"[MeSH] OR "Self Care"[MeSH] NOT letter OR review OR editorial OR meta-analysis OR "Heart-Assist Devices"[MeSH]) and Cochrane s query (Heart Failure, Congestive OR chronic heart failure OR heart insufficiency OR cardiac insufficiency OR cardiac failure AND Monitoring, Ambulatory OR home monitoring OR self monitoring OR Telemedicine OR telemonitoring OR home care OR outpatient management OR heart failure clinics OR Outpatient Clinics, Hospital OR Self Care). The study was limited to humans and a total of 831 Articles (PubMed) and 54 Articles (Cochrane) articles were obtained. II. Systematic review of the studies A group of inclusion and exclusion criteria were defined previously. With the 3
application of these criteria, on the final 12 articles were considered as valid. Initially, the articles we obtained were divided on 3 reviewer s groups, both containing 3 elements; each one read the articles of the group. To be included/excluded at least two reviewers s had to agree. (see articles selection flowchart below). a) Exclusion criteria Studies that did not evaluate the advantages of ambulatory or clinical monitoring were rejected, seeing as its acceptance would disobey to the primary aim inherent to this systematic revision. Also, the studies that didn t mention the methods used and the results were ignored because with them it wouldn t be possible do a systematic review. The articles that just presented results about costs were ignored as fine the studies that discussed clinical cases, drugs specific treatment or other factors influence. Articles comparing ambulatory and hospital monitoring were discarded, too. These were about other kinds of monitoring, reason by which they couldn t be considered in this systematic review. The studies that discuss ventricular therapeutics or data acquisition were also abandoned. Some articles were concerning supportive-educative intervention and technologies in improving heart failure-related self-care behaviour. These ones weren t accepted because of their outlying. At last, the articles not written in Portuguese, English, French or Spanish weren t read for the reason that it was impossible to realize their meaning. After the exclusion phase we obtained 125 Articles (Pubmed) and 13 Articles (Cochrane). b) Inclusion criteria The first inclusion criterion was choosing clinical trials of patients with heart failure using ambulatory monitoring. Studies that compared home with usual monitoring or clinical with usual monitoring were included because of their intimate relation and great importance to this systematic review. Studies about blood pressure, heart rate and oximetry monitoring were of a great meaning for the work once they gave a lot of precious information about the subject, so they were included. Those which mention the quality of life of population were included, once this parameter has an enormous value. Related articles were also searched in order to obtain all possible articles about our subject. 4
This inclusion phase resulted in 12 articles, 7 clinical trials comparing home monitoring with standard care and 5 daily clinics with usual care. c) Concordance analysis It was performed a Cohen Kappa (1960) and a SPSS inter-reviews reproductability tests, in the exclusion and inclusion phases. The concordance between the different reviewers of the three groups was evaluated. III. Data extraction and relevant criteria We gave attention to the baseline studies characteristics like age, sex, weight, blood pressure, their quality of life, and also mean time and type of intervention. Special attention was given to mortality and readmission rates, in each group. We defined the number of patients and the primary endpoints, too (see Table 1 below). So, we obtained the articles concerning some important quality criteria, such as the type of study (we only considered clinical trials to elaborate the meta-analysis) and the type of intervention was also a relevant point. The articles that didn t mention the methods used or didn t have the results and conclusions were discarded. The endpoints of each article were also analyzed in order to obtain the articles that evaluated important issues such as mortality and readmission rates and also the quality of life. Finally we extracted the outcomes to make sure that they were related to our study. IV. Data base creation Data related to the chosen articles were introduced on an electronic database, through SPSS 12.0 for Windows V. Statistical analysis All the analysis were conducted according to the intention-to-treat principle. Meta-analysis After verification if it was possible to perform a meta-analysis, we utilized the software named Review Manager 4.2.3 (RevMan 4.2) where we calculated the relative 5
risk (RR) random and 95% confidence intervals of the variables that we thought to be important for analysis, such as mortality and readmission rates. We also applied heterogeneity tests, in order to evaluate the validate of generalizations. Statistical significance was determined if the null hypothesis could be rejected at the P< 0,05 level. Results The twelve studies included a total population of 2513 (1133 in control and 1380 in the intervention group). Concerning the baseline characteristics, the men rate in global population was 70%, particularly in control group was 70% (SD: 14%; m: 41%; M: 84%) and the men rate in intervention group 69% (SD: 17%; m: 32%; M: 93%).The mean age of population was 68 years. The follow up time was 341 days. These two populations (control and intervention groups) were homogeneous concerning gender, age and heart failure degree (NYHA). According to our primary endpoints, hospital readmission and global cardiac mortality we obtained the following results: mortality rate in intervention group was 14% and in control group was 30%. The readmission rate in intervention group was 32% and the readmission rate of control group was higher (59%). What concerns about our secondary endpoint, the quality of patients life, 4 articles did not study it; 3 articles didn t have significant differences between the intervention and the control group and 5 articles described a better quality of life in the intervention group. On one hand, relating to articles that refer to home monitoring against usual care, from a total of 1405 patients followed up during a mean of 382 days we extracted results about the primary endpoints. The readmission rate in control group was 70% in opposition to 33% in intervention group. Moreover, the control group revealed a mortality of 38% while the mortality rate in intervention group was 18%. On the other hand, the 1108 patients that were evaluated in the comparative study about daily clinics with usual care had a mean follow up time of 285 days. The readmission rate in control group was 50% in opposition to the 31% readmission rate in other group. In addiction, mortality rate in control group was 18% and the mortality rate in second group just 9%. We executed a meta-analysis in order to compare home treatment and daily clinics, both with usual care concerning the primary endpoints defined. First, we divided 6
the articles in two groups, the first one included patients that were followed up for a period less than one year and the second one those that had a follow up time of one year or more. In relation to mortality, home monitoring comparing with the standard care revealed for the first group, home monitoring had a 26% RR reduction (RR 0,74 [IC95% 0,41;01,32]) than usual care and for the second one, the reduction in the RR (0,58 [IC95% 0,41;0,83]) for home monitoring was higher (42% reduction). The heterogeneity test showed that both populations were homogeneous (0% heterogeneity). Globally, the study favoured the home monitoring taking into account that the RR (relative risk) reduction was 38% (RR 0,62 [IC95% 0,46;0,84]). The results were statistically significant. (see figure 2 below) With the study of the association between daily clinics and usual care as far as mortality was concerned we obtained the following results: When we studied the relationship between daily clinics and usual care as far as mortality was concerned we obtained the following results: for the group followed up for less than 1 year there was a reduction of 33% in mortality for those patients that attended daily clinics comparing with the standard care (RR 0,67 [IC95% 0,47;0,97]). This population had 0% of heterogeneity. The second group had a 62% reduction of the RR (0,38 [IC95% 0,19;0,80]) for daily clinics and the heterogeneity revealed 65,7%. In total, the RR reduction for daily clinics was 45% (RR 0,55 [IC95% 0,41;0,75])and these results were also statistically significant. Concerning the readmissions we evaluated the home monitoring in comparison with standard care. In this study we were only able to collect two articles and so we were not able to divide in accordance to the scheduled follow-up time. The RR achieved was 0, 81 (IC95% 0,34;1,96). However the results were not statistically significant and the heterogeneity test was 97,7% and so no relevant conclusions were obtained. The comparison between daily clinics and usual care concerning the readmission rate, demonstrate a RR reduction in readmission for daily clinics patients of 33% (RR 0,67 [IC95% 0,56;0,81])for those which the follow up time was less than one year. The population was homogeneous (0% on the heterogeneity test). On the second group supervised, the RR reduction in readmission rates for patients attended at daily clinics was 63% (RR 0,37 [IC95% 0,09;1,54]). Nevertheless the heterogeneity test presented a high result (96%). we were only able to obtain statistically significant results for the population which was evaluated for a period of less than one year. We noticed with the inter-reviewers reproductability tests, that the total mean 7
result comparing the reviewers with the final decision was 0,758 which revealed concordance. Discussion and Conclusion During this work there were several restrictions that probably influenced the final results and conclusions. One of it was the difficulty in the definition of the query. Seven different queries were constructed with the purpose of integrate the most possible articles related to the theme of the work. Even though, and as other limitation, the number of articles included was reduced. Potentially, more articles could be incorporated, but some of them had a restricted access. From those, which were selected and found, other problems emerged on the extraction of raw data from the clinical trials. As for the primary endpoint of mortality a statistical significant reduction was found in the group of patients submitted to home monitoring or daily clinics monitoring when compared to standard care. Concerning the hospital readmission rate, there was a significant reduction in the intervention group submitted to daily clinics monitoring when the follow up was less than a year. No statistical difference was found in patients submitted to daily clinics monitoring followed for more than a year or for patients submitted to home monitoring. In the last case only two articles were collected, with a short population which may have contributed to the non significant results and no relevant conclusions extracted. The present study should be repeated, with a higher population, to confirm the results obtained and achieve others. Quality of life of patients with heart failure was our secondary endpoint of this work, although this is a difficult goal to measure/evaluate as not all articles mentioned it. Within every articles acquired, eight studied it, five of them described a better quality of life in the intervention group; the other three articles didn t have significant differences between the intervention and the control groups. The home monitoring or the daily clinics monitoring of such patients is extremely time and resources consuming [21]. So, more studies need to be performed in order to evaluate not only the efficacy of these two types of ambulatory monitoring but also with reference to the costs. Other point to consider is about improving different methods of patients management out of hospital, more economical and awarded of their financial possibilities and interests. These pioneering forms of care must be regarded as a mixture of advantages, for patients, improving their wellbeing and comfort, and to the hospitals, which have several benefits, like the reduced mortality 8
and better quality of life supported to their patients and also the money saved with the low percentage of readmissions. To confirm the results achieved, it is important to perform more studies evaluating these and other relevant endpoints, especially studies that establish the direct comparison between home monitoring and daily clinics. As a result, the best ambulatory treatment for chronic heart failure patients will be inferred. A three group study (these two types of ambulatory monitoring and standard care) is also important to be performed. Acknowledgments To doctor Altamiro Costa Pereira for his constructive and hopeful critics witch helped a lot during the work. To doctor Filipa Almeida, for the orientation, witch was crucial during all the work. Finally, to Dr. Luís Azevedo for the instructions about meta-analysis. References [1] Braunwald, et al. A textbook of Cardiovascular Medicine. Elsevier Saunders, 7th Ed, 509-539 [2] Hunt S et al. ACC/AHA 2005 Guidiline for the Diagnosis and MAnagement of CHF in the adult. JACC 2005; 38: 134-213 [3] Swedberg K et al. Guidelines for the diagnosis and treatment of Chronic Heart Failure. Eur. Heart J 2005; 26: 1115-1140 [4] Cleland JG, Swedberg K, Follath F et al. The EuroHeart Failure survey programmea survey on the quality of care among patients with heart failure in Europe. Part 1: patients characteristics and diagnosis. Eur Heart J 2003; 24: 442-463 [5] Ho K et al. The epidemiology of heart failure: the Framingham Study. JACC 1993; 22: 6-21 [6] Louis A et al. A systematic review of telemonitoring for the management of heart failure. Eur J Heart Failure 2003; 5: 583-590 [7] American Heart Association. Heart disease and stroke statistics: 2005 update. Dallas; American Heart Association 9
[8] Wilhelmsen L, Rosengren A, Eriksson H et al. Heart failure in the general population of men-morbidity, risk factors and prognosis. J Intern Med 2001; 249: 253-261 [9] Rich M et al. A multipledisciplinary intervention to prevent the readmission of elderly patients with congestive heart failure. NEJM 1995; 333:1190-95 [10] Ducharme A, Doyon O, et al. Impact of care at a multidisciplinary congestive heart failure clinic: a randomized trial. CMAJ 2005; 173(1): 40-45. [11] Cleland JG, Louis AA, et al. Noninvasive home telemonitoring for patiets with heart failure at high risk of recurrent admission and death. J Am Coll Cardiol 2005 ; vol. 45, No. 10. [12] Thompson DR, Roebuck A, et al. Effects of a nurse-led, clinic and home-based intervention on recurrent hospital use in chronic heart failure. Eur J Heart Fail 2005.; 7: 377-384. [13] Atienza F, Anguita M, et al. Multicenter randomized trial of a comprehensive hospital discharge and outpatient heart failure management program. Eur J Heart Fail 2004; 6:643-652. [14] Goldberg, et al. Randomized trial of a daily electronic home monitoring system in patients with advanced heart failure: The Weight Monitoring in Heart Failure (WHARF) trial. Am Heart J 2003; vol. 146, No. 4. [15] Capomolla S, Febo O, et al. Cost/utility ratio in chronic heart failure: comparison between heart failure management program delivered by day-hospital and usual care. J Am Coll Cardiol 2002; vol. 40, No. 7. [16] Kasper EK, Gerstenblith G, et al. A randomized trial of the efficacy of multidisciplinary care in heart failure outpatients at high risk of hospital readmission. J Am Coll Cardiol 2002; vol. 39, No. 3. [17] Lusignan S, Wells S, et al. Compliance and effectiveness of 1 year s home telemonitoring. The report of a pilot study of patients with chronic heart failure. Eur J Heart Fail 2001; 3: 723-730. [18] Ekman et al. Feasibility of a nurse-monitored, outpatient-care programme for elderly patients with moderated-to-severe, chronic heart failure. Eur Heart J 1998; vol 19: 1254-1260. [19] Capomolla S, Pinna G, e tal. Heart failure case disease management program: a pilot study of home telemonitoring versus usual care. Eur Heart J Suppl 2004; 6: F91- F98. 10
[20] A. Stromberg, J. Martensson, et al. Nurse-led heart failure clinics improve survival and self-care behaviour in patients with heart failure. Eur Heart J 2003 ; 24 : 1014-1023. [21] West J. A comprehensive management system for heart failure improves clinical outcomes and reduces medical resource utilization. Am J Cardiolog 1997; 79: 58-63 11
Figure 1- Articles selection flowchart 12
Table 1 - Baseline studies' characteristics 13
Figure 2- meta-analysis 14