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European Journal of Heart Failure 2004 6(5):643-652; doi:10.1016/j.ejheart.2003.11.023
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© 2004 European Society of Cardiology

Multicenter randomized trial of a comprehensive hospital discharge and outpatient heart failure management program

Felipe Atienzaa,*, Manuel Anguitac, Nieves Martinez-Alzamorad, Joaquín Oscab, Soledad Ojedac, Luis Almenarb, Francisco Ridoccia, Federico Vallésc and José A. de Velascoa

a Department of Cardiology, Hospital General Universitario de Valencia Valencia, Spain
b Department of Cardiology, Hospital La Fe Valencia, Spain
c Department of Cardiology, Hospital Reina Sofía Córdoba, Spain
d Department of Statistics, Universidad Politécnica de Valencia Spain

* Corresponding author. Present address: Servicio de Cardiología, Hospital General Universitario Gregorio Marañón, C/Dr Esquerdo, 46, 28007 Madrid, Spain. Tel.: +34-915868281; Fax: +34-915868291. E-mail address: fatienzaf{at}meditex.es


   Abstract
Top
 Notes
 Abstract
1. Introduction
 2. Methods
 3. Results
 4. Discussion
 References
 
Aims: Disease management programs can reduce hospitalizations in high-risk heart failure (HF) patients, but generalizability to the population hospitalized for HF remains to be proven. We aimed to assess the effectiveness of a discharge and outpatient management program in a non-selected cohort of patients hospitalized for HF.

Methods and results: Patients admitted with decompensated HF were randomized to receive usual care (n=174) or an intervention (n=164) consisting of a comprehensive hospital discharge planning and close follow-up at a HF clinic. After a median of 509 days, there were fewer events (readmission or death) in the intervention as compared with the control group (156 vs. 250), which represents 47% (95%CI: 29–65; P<0.001) event reduction per observation year. At 1-year, time to first event, time to first all-cause and HF readmission, and time to death were increased in the intervention group (P<0.001). All-cause and HF readmission rates per observation year were significantly lower, quality of life improved and overall cost of care was reduced in the intervention group.

Conclusions: This comprehensive hospital discharge and outpatient management program prolonged time to first event, reduced hospital readmissions, improved survival and quality of life of patients hospitalized for HF, while reducing cost of management.

Key Words: Heart failure • Disease management programs • Heart failure clinic • Readmissions • Mortality

Received August 15, 2003; Accepted November 7, 2003


   1. Introduction
Top
 Notes
 Abstract
 1. Introduction
2. Methods
 3. Results
 4. Discussion
 References
 
Heart failure is a chronic, progressive disease characterized by frequent hospital admissions and high mortality rates [1]. It is the leading indication for hospitalization in older adults, and discharge rates are steadily increasing [1,2]. Despite advances in pharmacological treatment, heart failure is still associated to a huge requirement for hospitalization, with readmissions rates ranging from 29 to 59% within 6 months after discharge [1,3]. As a consequence, quality of life for heart failure patients is markedly impaired and cost of management is exceedingly high [1,4].

The introduction of more effective drugs to improve outcome together with the high prevalence of comorbid conditions, has led to an increasingly complex polypharmacy. However, both physicians and patients compliance is less than optimal and opportunities exist for improvement [4]. Lack of adherence to prescribed medical regimen has been identified as the most common precipitating factor for relapse of congestive heart failure [5,6]. Other factors leading to hospital admission could also be preventable, such as inappropriate use of drugs, poor follow-up controls after discharge or delay in seeking care [5–7]. Overall, approximately 52% of heart failure admissions could be regarded as preventable [6].

The above mentioned limitations of current heart failure treatment patterns have provided the basis for the development of new strategies, such as disease management programs. These programs are usually multidisciplinary, but vary in the nature of the intervention and can have distinct approaches [8]. Recent randomized reports, including a well-designed meta-analysis, have shown that disease management programs can reduce hospitalizations, although results vary from one study to the other, and the impact on mortality and quality of life are not conclusive [9–12]. Moreover, the applicability of these interventions to the general population of patients with heart failure is still unknown, due to the fact that most published studies had small sample size (≤200 patients in most of cases), [10,11] had focused on high-risk patients [9–11], had limited follow-up duration, [9] varied in the nature and intensity level of the intervention, [8] and have been conducted at single and highly specialized centers [12].

The objective of this randomized multicenter study was to assess the effectiveness of an intervention program consisting of a comprehensive hospital discharge planning, easy availability for consultations and close follow-up at a heart failure clinic. We hypothesized that this intervention would prolong time to first event and reduce hospital readmissions among a non-selected cohort of patients discharged with the diagnosis of congestive heart failure, as compared to usual care.


   2. Methods
Top
 Notes
 Abstract
 1. Introduction
 2. Methods
3. Results
 4. Discussion
 References
 
2.1. Study sample
The PRICE (Prevención de Reingresos por Insuficiencia Cardíaca en España) multicenter study was conducted at three tertiary referral University Hospitals in Spain. All patients discharged with the primary diagnosis of congestive heart failure from the cardiology wards were considered eligible. The diagnosis of heart failure was based on the presence of symptoms and signs of heart failure in conjunction with objective evidence of major cardiac dysfunction at rest [13]. The exclusion criteria from the study were expected survival of less than 3 months, discharge to a nursing home or long-term care facility, home distance from the hospital >30 km, impossibility to contact by telephone, dementia or psychiatric illness, and inclusion on to a waiting list for invasive cardiology or heart surgery at discharge. The study was approved by the institutional ethical committees of the participating centres.

2.2. Randomization and data collection
Within 48 h prior to discharge, the cardiologists responsible for the in-hospital management of heart failure patients, contacted an independent assistant who screened patients for eligibility, obtained written informed consent and proceeded to allocate patients to usual care or to the intervention group using a computer-generated randomization list [14]. To ensure an adequate balance in the number of participants receiving each intervention in a priori high risk (65 years or older) or underrepresented subgroups (women), a blocked stratified randomization was performed according to age and sex. Baseline clinical data and pharmacological treatment at discharge were recorded. Quality of life was assessed using the Minnesota living with heart failure questionnaire [15].

2.3. Interventions
On admission, all patients with heart failure considered for inclusion were managed by the responsible cardiologist according to guidelines published at the time of designing the study [13].

The intervention program consisted of three phases. In the first phase, the patients and their families received formal education about the disease. Prior to discharge, the research cardiac nurse had an in-depth interview with the patient and caregivers. Specifically, the nurse assessed the patient knowledge of the disease, the ability to identify signs and symptoms of heart failure worsening, and the most common responses to the situations of deterioration. Special emphasis was done in the identification of circumstances that predicted a higher risk for poor discharge outcomes in a similar population [16]. This education session included explanations of symptoms and signs of heart failure decompensation, importance of self-monitoring of vital signs, diet and exercise counselling, effects of medications and importance of compliance, and measures to be taken in case of worsening. Individualized strategies were used to improve treatment adherence and to empower patients to manage health problems (i.e. diuretic self-adjustment). All this process was supported by using a teaching brochure developed by the study investigators. The patient was discharged home by the responsible cardiologist who prescribed treatment without knowledge of the assignment group.

In the second phase, a visit with the primary care physician was scheduled within 2 weeks of discharge. The aims of this visit were to monitor patients’ clinical progress, identify incipient physical signs of decompensation, and reinforce the educational knowledge. When the patient showed clinical signs of worsening, the primary care physician was allowed either to modify the discharge treatment or to refer the patient to the hospital for reassessment.

During the third phase, regular follow-up visits at the outpatient Heart Failure Clinic were scheduled every 3 months where, in addition to the routine clinical assessment, the cardiologist reviewed the patients’ performance and introduced correcting strategies to improve treatment adherence and response. This visit reinforced patients’ knowledge of the illness and increased their ability to manage health problems. The heart failure specialist coordinated visits to other specialists, diagnostic tests and treatments prescribed by other instances. The telemonitoring phase lasted from discharge until the end of the study and consisted of a facilitated telephone communication with a monitor (SCT), providing a 24-h mobile phone contact number. The heart failure clinic team was also available for consultation during working hours. Patients were instructed to contact the monitor or the heart failure team in case of doubts or signs of worsening.

Control group patients received discharge planning according to the routine protocol of the study hospitals. To avoid contamination of the control group management, additional follow-up was performed by primary care physicians and cardiologists not participating in the study. Additional details about standard of care of heart failure patients in Spain can be found elsewhere [17].

2.4. Outcomes
Decisions about rehospitalization of all participating patients experiencing any symptomatic deterioration were made by independent physicians at the hospital emergency rooms. The primary outcome measure was event-free survival, defined on the basis of time to first event (any cause readmission or death) at 1 year. Secondary endpoints were rate of all-cause and heart failure readmissions per observation year, rate of death per observation year, time to first all-cause and heart failure readmission, time to death, quality of life 1 year after the index admission, and cost of management.

Outcome data were obtained from patients, their families, hospital records, and regional death registries. The Hospital Accounting Departments provided the rate of the daily average cost of for each Diagnosis-Related Group (DRG). The mean cost for hospitalization was 451 euros ({euro}) per day. The cost of the study intervention was calculated for the whole intervention group, and included a full-time cardiologist yearly salary ({euro}29 789), nursing time at an estimated hourly rate of {euro}40, telephone calls made to the monitor estimated at {euro}10 and infrastructure requirements (e.g. mobile telephones, brochures). Cost associated with screening, randomization, and out-of-hospital costs of management were not included.

2.5. Sample size
Using the results of a previous observational study performed in a similar population of heart failure patients, we estimated that 158 patients had to be included in each group in order to the log-rank test detect a hazard ratio of 0.6 (2-sided {alpha}=0.05 and power 0.90), based on the assumption of a 55% yearly rate of readmission or death for the control group [16,18].

2.6. Statistical methods
All analyses were conducted according to the intention-to-treat principle. Baseline data for intervention and control groups were compared using {chi}2 tests for categorical variables, Student t tests for normally distributed continuous variables and the Wilcoxon rank sum test for abnormally distributed variables. Kaplan–Meier survival curves and log-rank test were used to compare control and intervention groups for the primary end point of time to first event (readmission or death) and the secondary outcomes of time to first readmission for any reason and time to first readmission for heart failure. Additionally, survival curves were punctually compared at the end of the first year by normal approximation [18]. The standard error of the Kaplan–Meier estimation was obtained using the Greenwood formulae. A stepwise regression was performed using the Cox proportional-hazards model to determine whether assignment to the intervention group was an independent predictor of the primary and secondary endpoints after adjustment for other relevant covariates. Covariates were selected at a {alpha}=0.05 univariate level of significance and removed at a {alpha}=0.10 level of significance. Risk ratio estimations and 95% confidence intervals were calculated to study the effect of the different covariates on the endpoints. Unbiased estimations of the rate of events per observation year were obtained by dividing the number of events and the sum of the individual times of observation. An approximate normal test for the equality was used to compare the rates [18]. Analysis were performed using SPSS for Windows (version 10.0).


   3. Results
Top
 Notes
 Abstract
 1. Introduction
 2. Methods
 3. Results
4. Discussion
 References
 
3.1. Study sample
From January through June 1999, a total of 572 patients planned to be discharged with the primary diagnosis of congestive heart failure were screened for inclusion in the study (Fig. 1). Among them, 234 (41%) met at least one exclusion criteria. Inclusion on to waiting list for cardiac surgery or other invasive procedure (43%), followed by patient or responsible physician refusal (19%) and participation in other clinical trial (15%) were the most common causes for exclusion.


Figure 1
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  		Fig. 1 Patient flow diagram.

 
All patients were followed for a median of 509 days (IQR: 365–649). During follow-up, two patients (one in each group) were admitted to a long-term care facility. According to the intention-to-treat principle, these patients were analyzed as allocated, but were censored at the time of admission to the nursing home.

3.2. Baseline clinical and demographic characteristics
A total of 338 patients met the inclusion criteria and were randomized to receive usual care (n=174) or to undergo the proposed intervention (n=164). Both groups were similar with respect to all baseline characteristics (Table 1). The median age of the entire sample was 68 (IQR: 59–74) years and 60% were men. The most common cause of heart failure was ischemic heart disease in 98 (29%) patients. Other less frequent causes of heart failure were recorded in 33 (10%) patients. Prior to hospitalization half of the patients were in NYHA class III or IV and 48% had been previously admitted to the hospital. The median ejection fraction was 40% (IQR: 30–55%), and it was below the normal range in three-quarters of the patients. There were no differences in the pharmacologic treatment administered at discharge.


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  		Table 1 Baseline clinical and demographic characteristics of the study patients

 
3.3. Event-free survival
During the observation period, there were 51 deaths and 199 readmissions (250 events) in the control group, and 30 deaths and 126 all-cause readmissions (156 events) in the intervention group. The rates per year of observation were 117 events per 100 patients in the control group and 70 events per 100 patients in the intervention group (Table 2). These results represent a reduction of 47 events per 100 patients (95%CI: 29–65; P<0.001) per year of observation, in patients assigned to the intervention group.


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  		Table 2 Rates of events, readmission and death per year of observation

 
As shown in Fig. 2, time to first event was increased in the intervention group, and the difference remained significant throughout the overall study follow-up (log-rank test: P<0.001). At 1 year, the probability of remaining free of events was significantly higher in the intervention (0.62; 95% CI: 0.55–0.69) as compared with the control group (0.40; 95% CI: 0.33–0.48; P<0.001). Independent predictors of event-free survival in the Cox-proportional hazards model are shown in Fig. 2. The effect of the intervention on time to first event remained significant after adjusting for possible confounding factors.


Figure 2
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  		Fig. 2 Cumulative probability of event-free survival during follow-up. Independent predictors: relative risk (95% Confidence Interval). Level of significance: *P<0.001; **P<0.01.

 
3.4. Readmissions
During the observation period, 101/174 patients in the control group and 68/164 patients in the intervention group were readmitted. The rates of readmitted patients for any cause per year of observation were 0.47 and 0.31, respectively (Table 2). These results represent a 16% (95% CI: 4–28%; P=0.004) reduction in the rate of readmitted patients for any cause with the intervention program. With respect to the number of all-cause readmissions, there were 199 readmissions in the control group, as compared with 126 in the intervention group. The rates per year of observation were 93 and 56 all-cause readmissions per 100 patients, respectively. These results represent a reduction of 37 all-cause readmissions per 100 patients (95% CI: 21–53; P<0.001) per year of observation for the intervention group.

As shown in Fig. 3, time to first all-cause readmission was increased in the intervention group (log-rank test: P<0.001). At 1 year, the estimated probability of not being readmitted 0.45 (95% CI: 0.38–0.53) in the control group and 0.66 (95% CI: 0.59–0.73; P<0.001) in the intervention group. Assignment to the intervention group was independently associated with an increased time to all-cause first readmission after adjustment for baseline characteristics.


Figure 3
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  		Fig. 3 Cumulative probability of all-cause readmission during follow-up. Independent predictors: relative risk (95% Confidence Interval). Level of significance: *P<0.001; **P<0.01; ***P<0.05.

 
During follow-up, 79/174 control group patients were readmitted due to heart failure as compared with 39/164 in the intervention group. The rates of readmitted patients per year of observation were 0.37 and 0.18, respectively (Table 2). These results represent a 19% (95% CI: 0.09–0.29; P<0.001) reduction in the rate of readmitted patients for heart failure with the intervention program. Overall, 183 of 325 readmissions were due to worsening heart failure (56%). In the control group, there were 122/199 readmissions for recurrent heart failure as compared with 61/126 in the intervention group. The rates per year of observation were 57 and 27 heart failure readmissions per 100 patients, respectively. These results represent a 30% (95% CI: 18–42; P<0.001) reduction in the rate of heart failure readmissions per observation year for the intervention group.

As shown in Fig. 4, time to first readmission for heart failure was increased in the intervention group (log-rank test: P<0.001). At 1 year, the probability of not being readmitted due to heart failure was significantly higher for the intervention group (0.76; 95% CI: 0.70–0.83) as compared with the control group patients (0.55; 95% CI: 0.48–0.63; P<0.001). This difference remained significant throughout the whole study follow-up. Assignment to the intervention group was independently associated with an increased time to first heart failure readmission after adjustment for baseline characteristics.


Figure 4
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  		Fig. 4 Cumulative probability of heart failure readmission during follow-up. Independent predictors: relative risk (95% Confidence Interval). Level of significance: *P<0.001.

 
Readmissions for reasons other than heart failure were also more frequent in the control group (77/199) as compared with the intervention group (65/126), although the difference was not significant. The proportion of patients with multiple readmissions (≥2 times) was slightly lower in the intervention group (20%; 33/164) as compared with the control group (28%; 48/174), but this difference did not reach statistical significance (P=0.11).

3.5. Mortality
At the end of follow-up, 51/174 patients died in the control group as compared with 30/164 patients in the intervention group. Death rates per observation year were 0.24 and 0.14, respectively (Table 2). As shown in Fig. 5, intervention group patients were less likely of dying than control group patients during the observation period (log-rank test: P=0.017). After adjusting for baseline differences between groups and other prognostic factors, the independent predictors of death at the end of follow-up were age, previous limitations for dailylife activities, and the diagnosis of heart failure due to valvular heart disease.


Figure 5
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  		Fig. 5 Cumulative probability of survival during follow-up. Independent predictors: relative risk (95% Confidence Interval). Level of significance: *P<0.001; **P<0.05.

 
3.6. Quality of life
At discharge, 11 patients failed to complete the quality of life questionnaire, six (4%) in the intervention group and five (3%) in the control group (P=ns). The most common reason for not answering the questionnaire was patient refusal. At baseline, quality of life scores were similar for both groups (Fig. 6). After 1-year follow-up, a total of 220 of the 257 surviving patients completed the questionnaire. There was a general improvement in the health-related quality of life. Although the quality of life scores improved in both groups at 1 year, the improvement was significantly higher in the intervention as compared with the control group.


Figure 6
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  		Fig. 6 Changes in quality-of-life scores from baseline to 1 year follow-up, assessed with the Minnesota living with heart failure questionnaire. Higher scores indicate worse quality of life (range 0–105). Values shown are mean with error bars representing standard deviation.

 
3.7. Cost of management
The intervention resulted in a net reduction in hospital use of 51% (total number of days of hospitalization: 2090 in the control group vs. 1059 in the treatment group), mainly due to a significant reduction in the number of CHF days of hospitalization in the intervention group (1394 vs. 500). As a result, the costs of hospital readmissions were higher in the control group by an average of {euro}2505 per patient ({euro}5.417 in the control group vs. {euro}2.912 in the intervention group). The average cost of the study intervention during the follow-up period was {euro}442 per patient. Therefore, the overall cost of care was reduced in {euro}2063 per patient in the intervention group.


   4. Discussion
Top
 Notes
 Abstract
 1. Introduction
 2. Methods
 3. Results
 4. Discussion
References
 
This study demonstrates that a comprehensive hospital discharge and outpatient heart failure management program can lengthen the time to first readmission or death, reduce all-cause and worsening heart failure readmissions, improve survival and quality of life, and decrease cost of care among patients discharged for congestive heart failure. Our findings give further support to the recommendations of several guidelines and health agencies, that strongly encourage the establishment of disease-management programs for heart failure patients [4,8,19]. To our knowledge, this is the first multicentre heart failure disease management program reported to date.

Heart failure management programs have received increasing interest and the results of several well-designed, randomized heart failure management trials are now available, [9–11] [20–26] and have been reviewed [8] and meta-analyzed [12,27]. Most trials, mainly those that used a multidisciplinary team and specialized follow-up procedures, have reported a reduction in rehospitalization rates, ranging from 22 to 45% [12] However, the upper limit of the 95% confidence interval was less than the unit in only 2 studies, perhaps due to differences in design and limited sample size [9,21]. In the overall meta-analysis, readmissions were significantly reduced by 13% [12]. Recent studies with extended follow-up duration have reported positive [25,27] or neutral [26] outcomes. Despite the consistency of findings among these studies, several doubts persist about the impact of the interventions on event-free survival and the generalizability of their results.

Our findings confirm and extend the beneficial effects of these programs to a non-selected population of patients hospitalized for decompensated heart failure managed by cardiologists in our country. The magnitude of the beneficial effects of the intervention used in the present study was significant and similar to previous studies [9–12,25]. The intervention we proposed was at least as effective in reducing both all-cause and heart failure readmission rates. The success of the intervention was largely due to the effective prevention of worsening heart failure readmissions, which represent more than 50% of all admissions in our study. Furthermore, intervention patients also showed a significantly longer readmission-free survival. Although most previous studies have consistently shown improvements on hospitalization rates, the effect on event-free survival and mortality was not conclusive. Some [9,10,22,25,27] but not all [11,20,26] studies have been able to show a prolongation of the time to first readmission or death. This lack of concordance probably reflects differences in the type of intervention, follow-up time or selection criteria. Our findings confirm the ability of the intervention to reduce the frequency of events and delay the first readmission or death.

We have found a positive impact of the intervention on survival. Nevertheless, the improvement in survival rates in our study was not independently associated with the intervention. We are unable to explain the reasons for the differences in survival, but factors other than chance may have played a role. The extended follow-up of a conglomerate study of 2 separate cohorts also found a strong trend to a prolonged survival in patients assigned to a home-based intervention [27]. No other trial or meta-analysis has found a significant influence of the intervention in terms of mortality [12]. Further studies are warranted to verify the possible survival benefit attributable to disease management programs.

According to other studies [9–11,26], quality of life improved in the surviving patients of the intervention group that were able to complete the questionnaire 1 year after inclusion in the study. Nevertheless, other investigators failed to demonstrate significant quality of life improvements despite better outcomes in other parameters [12,20,22,24]. In our study, the beneficial effects of the intervention could offset the negative impact of diet or management restrictions.

4.1. Consideration of possible beneficial mechanisms
There is considerable diversity among outpatient heart failure management programs [8]. With the exception of one study, most interventions have consistently shown some degree of benefit on patient outcomes [12,24]. Although we are unable to identify which elements of the intervention are responsible for these beneficial results, several reports suggest that the major components of our intervention could explain an important proportion of the beneficial effects [12,22,25].

The intervention we have used was based on a physician directed specialty heart failure clinic model, in which nurse coordinators assist with patient education and management [8]. A recent report has demonstrated the independent value of an education and support intervention program based on similar assumptions [25]. The discharge planning implemented in our study facilitated the patient's successful transition into the outpatient setting. An effective transitional care program is better achieved when the intervention is initiated early during hospital admission [22]. Other investigators have documented problems such as early readmission or death when the intervention is postponed to 7–14 days after discharge [10]. Several studies provide additional evidence of the effectiveness of ongoing assessment of clinical stability after discharge to reduce readmissions rates [9,12,22,25].

Our intervention program complies with the recommendations of experts and health agencies, but has some distinct features [8]. All study patients were managed by a cardiologist and received treatment according to guidelines. We did not perform home visits nor scheduled telephone contacts after discharge, but a monitor was always available for telephone consultations.

4.2. Limitations of the present study
Although most baseline clinical and demographic characteristics were similar to those in previous studies, our patients were slightly younger (median 68 years), exclusively white race and had a higher proportion of heart failure due to valvular heart disease. These distinguishing characteristics reflect the clinical profile of the patients admitted with heart failure to the Cardiology Departments in our country [16,17]. Most demographic characteristics are similar to those of patients hospitalized for congestive heart failure and cared for by cardiologists in the US and Europe [11,28]. Nevertheless, further studies are needed to confirm the applicability of our intervention to the elderly patients included in other studies or treated by generalist physicians [9,11,12].

A second limitation is the relatively small sample size of the trial, although it was larger than any other published intervention program specifically designed for heart failure patients [12] The third limitation is that the cost-analysis performed was not comprehensive and did not account for non-hospital cost or medications costs. Nevertheless, previous studies showed that hospital costs were responsible for the major differences favouring the intervention [9,22]. The high reduction in hospital admissions obtained and the relatively inexpensive medium-intensity intervention used, made the proposed management program highly cost saving [9–12,20,22,25].

In summary, our intervention program, based on predischarge patient education, self-management guidelines, easy availability for patient consultations and close follow-up at a heart failure clinic can significantly prolong time to first event, reduce hospital readmissions, improve survival and quality of life of patients hospitalized for decompensated heart failure. This intervention has the potential to significantly improve outcomes while reducing cost of management. This multicentre study extends and further supports the favourable results of previously reported single institution trials.


   Acknowledgements
 
Other PRICE study participating investigators: José V. Albero, MD, Víctor Palanca, MD, Javier Jiménez, MD, Carlos Soriano, MD, Anastasio Quesada, MD, Eugenia Lozano, RN, Carmen Ramos, RN, Manuela Martínez, RN, collected data, provided care and monitored patients. We are indebted to the primary care physicians that collaborated in out-of-hospital patient management. Dr. Atienza was funded by the Spanish Society of Cardiology, Madrid, Spain. Prof. Martinez-Alzamora was funded by a Research Incentive Program from the Polytechnic University of Valencia, Spain. Merck, Sharp & Dohme contributed financially to the edition and printing of the brochure for heart failure patients used in the study.


   Notes
Top
 Notes
Abstract
 1. Introduction
 2. Methods
 3. Results
 4. Discussion
 References
 
{star} These authors belongs to the PRICE study group. Back


   References
Top
 Notes
 Abstract
 1. Introduction
 2. Methods
 3. Results
 4. Discussion
 References
 

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