controlled trial, Cardiac Rehabilitation in Ad- vanced Age (CR-AGE), are to examine the effects of an 8-week comprehensive cardiac rehabilitation intervention ...
Aging Clin. Exp. Res. 10: 368-376, 1998
Aims, design and enrollment rate of the Cardiac Rehabilitation in Advanced Age (CR-AGE) randomized, controlled trial F. Fattirolli1, A. Cartei1, C. Burgisser1, G. Mottino1, F. Del Lungo1, N. Oldridge2, S. Fumagalli1, L. Ferrucci3, G. Masotti1, and N. Marchionni1 1Department of Gerontology and Geriatric Medicine, University of Firenze, Firenze, Italy, 2Department of Health Sciences, University of Wisconsin-Milwaukee, U.S.A., 3INRCA Department of Geriatric Medicine, Firenze, Italy
ABSTRACT. Data regarding the efficacy of cardiac rehabilitation after acute myocardial infarction in advanced age are limited, and are derived from either controlled but non randomized trials, or observational studies. Several aspects of cardiac rehabilitation after myocardial infarction in advanced age, including its effectiveness on exercise tolerance and health-related quality of life, as well as the feasibility of rehabilitation programs, need clarification. The objectives of this randomized, controlled trial, Cardiac Rehabilitation in Advanced Age (CR-AGE), are to examine the effects of an 8-week comprehensive cardiac rehabilitation intervention, comparing 1) supervised outpatient, hospital-based cardiac rehabilitation, 2) homebased cardiac rehabilitation, and 3) usual care in each of three groups of post-myocardial infarction patients, 45-65, 66-75, and 76-85 years of age. The primary objective of the trial is to evaluate the change in physical fitness in each age group assessed by total work capacity at the end of the intervention, and during follow-up over both the medium- (6 months) and the long-term (1 and 2 years). Secondary objectives of the trial include an examination of the feasibility of cardiac rehabilitation in older patients, as well as the determination of the following: exercise complication rates; changes in peak oxygen consumption; changes in other outcome measures, such as health-related quality of life, prevalence of anxiety and depressive symptoms, fluid intelligence, body composition and mass index; incidence of new cardiac and non-cardiac events; and utilization rates of health care services. Enrollment in the CR-AGE trial is
expected to be completed within the first half of 1998. (Aging Clin. Exp. Res. 10: 368-376, 1998) ©1998,
Editrice Kurtis
INTRODUCTION Controlled and observational studies have demonstrated several short- and long-term favorable effects of cardiac rehabilitation (CR) in patients with ischemic heart disease, although the strength of the scientific evidence is variable (1). Comprehensive, multifactorial CR, including exercise training, counseling, education and behavioral interventions, not only enhances exercise tolerance and improves psychological wellbeing, but also reduces coronary risk factors, and decreases long-term cardiovascular and all-cause mortality (1). Indeed, on the basis of an extended review of the literature, the Clinical Practice Guidelines panel (1) stated that multifactorial CR services should be considered an integral component of the contemporary management of patients with multiple presentations of coronary heart disease. Although the evidence for a decreased mortality with multifactorial CR after myocardial infarction (MI) is limited by the relatively small sample sizes in most of the randomized controlled trials (2-7), by using the technique of meta-analysis Oldridge et al. (8) and O’Connor et al. (9) could demonstrate an approximately 25% relative reduction in 3-year mortality among patients randomized to CR. However, the results of these meta-analyses cannot be generalized to the older population. Indeed, virtually all of the randomized controlled trials selected for pooled analysis employed age-based exclusion criteria (8, 9); of
Key words: Aging, cardiac rehabilitation, exercise, ischemic heart disease, myocardial infarction. Correspondence: N. Marchionni, M.D., Istituto di Gerontologia e Geriatria, Università di Firenze, Via delle Oblate 4, 50141 Firenze, Italy
Cardiac rehabilitation after MI in advanced age
the more than 4300 patients in the trials, 25% were younger than 55 years (9), 93% were younger than 65 (9), none were older than 71, and only 3% were women (8, 9). The results of observational studies, including patients as old as 90 years and as many as 30% women (10-17), suggest that training after MI enhances exercise tolerance to a similar extent in men and women, and in all age groups. However, though 31% of 778 patients enrolled in the largest and most recent observational study of CR (10) were older than 65 years, only 6% were older than 75. Furthermore, although 28% were women, only incomplete exercise test data were reported on the 10 women older than 74 years. Only two controlled trials of CR have explicitly compared the effect of CR between different age groups (18, 19) and genders (19). Exercise tolerance increased in both trials, with no difference in the relative increase between patients younger and older than 65 (18) or 70 (19) years of age, nor between older male and female patients (19). However, both trials were not randomized, and enrolled only a limited number of patients. Since a large percentage of patients who need CR belong to the oldest age groups, the lack of reliable information on its effectiveness in advanced age is particularly problematic. Indeed, coronary artery disease in persons older than 65 years accounts for more than 80% of cardiac deaths, and more than 50% of all MI (20), with a longer hospital stay (21) and greater subsequent disability among older individuals (22). Moreover, older cohorts in the geriatric population are significantly different from younger ones in terms of health care needs (23). Thus, randomized controlled trials specifically aimed at assessing the efficacy, the most appropriate program design, the feasibility and the cost-effectiveness of CR in advanced age are important objectives for new clinical research (1). The design of these trials poses new challenges to clinical investigators. In particular, the geriatric literature has pointed out that compliance is one of the major barriers that may limit the efficacy of exercise programs in older populations (24). Among the alternative approaches to the delivery of CR services that are receiving increasing attention (1), home-based exercise training might increase compliance. This approach appears to be safe, efficacious, and cost-effective in increasing the functional capacity and improving the emotional state of selected low-risk, middleaged patients with a recent MI (25-27). But again, there are limited data regarding its safety, efficacy and
Furthermore, most of the geriatric literature suggests that the effectiveness of medical interventions in older patients should be evaluated in terms of quality of life, and the patient’s perceived health-related quality of life (HRQL) is being increasingly used as a major indicator of the quality of medical care. In theory, CR may have positive effects on the global functional status, and on several components of HRQL (30-32). Nevertheless, global and specific measures of HRQL have received little attention as outcomes of CR (33, 34). To address these problems, we have designed a randomized controlled trial, the Cardiac Rehabilitation in Advanced Age (CR-AGE) trial, with the specific purpose of comparing the effects of outpatient, hospital-based and home-based CR in patients aged 45-65, 66-75 and 76-85 years. STUDY DESIGN The CR-AGE is a randomized, controlled trial that compares the effectiveness of three interventions – namely supervised outpatient, hospital-based CR (OCR), home-based CR (HBCR), and usual care – within each of three age groups, 45-65, 66-75 and 76-85 years. We distributed the younger population into two age groups (45-55 and 56-65 years) to ensure that the different treatment groups would be balanced, while the age of 75 years was selected because it discriminates on the basis of qualitative and quantitative health care needs (23). Within each age group, it was decided to select a proportion of men and women that would reflect a gender distribution similar to that observed in the overall population that attended CR programs at the Department of Gerontology and Geriatric Medicine of the University of Firenze during the previous year (Table 1). Post-MI patients discharged from some of the intensive care units in the Firenze area are usually referred to the outpatient clinic of this Department for functional assessment and possible CR. Recruitment in the CR-AGE is based on such referrals. Since our outpatient clinic is the only rehabilitation center in a relatively large area, it can offer CR programs only to a small part of the potentially eligible patients; therefore, despite the previously demonstrated benefits of CR on several primary outcomes in younger post-MI patients (8, 9), the allocation of some subjects to a control group was not considered unethical. This study was approved by an ad hoc ethics committee. Patients’ informed consent is systematically obtained, and a letter describing the training program is sent to their physicians. All 45- to 85-year-old patients with a diagnosis of recent (4-6 weeks) MI are considered eligible and are
F. Fattirolli, A. Cartei, C. Burgisser, et al.
Table 1 - Distribution of study population in the CR-AGE trial. Age (years)
Intervention
Patients (N)
Male (N)
Female (N)
76-85
OCR
30
18
12
76-85
HBCR
30
18
12
76-85
Usual care
30
18
12
66-75
OCR
30
20
10
66-75
HBCR
30
20
10
66-75
Usual care
30
20
10
45-55 56-65
OCR
30
9 17
1 3
45-55
HBCR
30
9
1
the study protocol, showing the inclusion/exclusion criteria and the data collection schedule is shown in Figure 1 (35-51). Enrolled patients in each of the three age groups are randomly assigned to one of the three intervention groups, following a randomized block design. Investigators and technicians performing study evaluations both at baseline and during follow-up are unaware of patient assignment. Objectives The primary objective of the CR-AGE trial is to examine the efficacy of an 8-week program of comprehensive CR after MI to improve exercise tolerance in each of three age groups (45-65, 66-75, and 7685 years) with patients randomly assigned to either OCR, HBCR, or usual care. Exercise tolerance is determined as the total work capacity (TWC, Kg·m) by a symptom-limited exercise stress test. Secondary objectives of the trial include an assessment of the feasibility of CR (in terms of exclusion rate from, and adherence rate to the trial), as well as the determination of the following: exercise complication rates; changes in peak oxygen consumption (VO2 peak, mL/min/kg) and in other outcome measures such as HRQL, prevalence of anxiety and depressive symptoms, fluid intelligence, and body composition; incidence of new cardiac and non-cardiac events, and utilization rates of health care services. All the participants are evaluated at baseline, at the end of the 8-week intervention, and then after 6, 12 and 24 months. Sample size estimation Sample size has been estimated using data from a
compared changes in TWC in patients younger and older than 65 years undergoing CR. It was estimated that drop-outs during the 8-week CR program, to be included in the original allocation group because of the intention-to-treat principle, would not exceed 10%. It was assumed that the change in TWC in each group would be normally distributed, with an average standard deviation of 1,600 Kg·m (18), and that all statistical tests would be carried out at the two-sided 0.05 significance level. With these assumptions, a sample size of 30 individuals would be sufficient (power=0.90) to detect an increase in TWC of 1,364 Kg·m from baseline in patients younger and older than 65 years with 8 weeks of rehabilitation. This difference is similar to that observed in our previous controlled study (18). As there are data showing that the percent increase in TWC with CR is similar in patients under and over the age of 70 years (19) and, albeit with small numbers of patients, even over the age of 75 (17), we assumed that these sample size estimations would also apply to patients older than 75 years. Treatments The established guidelines of the American College of Sports Medicine for intensity, frequency, duration, and mode of aerobic exercise training are utilized in both interventions in the trial (52). Supervised outpatient hospital-based cardiac rehabilitation. Patients take part in the 8-week OCR program five days each week. The program consists of 24 sessions (3/week) of endurance training on a cycle ergometer (5-minute warm-up, 20 minutes of training at a constant workload, with blood pressure recorded every 5 minutes, 5-minute cool-down; 5-minute postexercise observation period to monitor the cardiovas-
Cardiac rehabilitation after MI in advanced age
Eligible patients: 4-6 weeks post-AMI age 45-85 years
Exclusion criteria? No
- MMSE
