Volume 33, Issue 2 , Pages 202-207, February 2007
A Non-randomised Controlled Trial of the Clinical and Cost Effectiveness of a Supervised Exercise Programme for Claudication
Article Outline
Objectives
The main aims of treatment in patients with intermittent claudication (IC) are to improve the clinical indicators of lower limb ischaemia and patients' quality of life (QoL). The aims of this study were assess the clinical and cost effectiveness of a supervised exercise programme (SEP) in patients with IC.
Design
Non-randomised, controlled trial.
Setting
University teaching hospital.
Patients and methods
Two groups of patients with IC were studied. Seventy patients were sequentially recruited before and after the establishment of a Supervised Exercise Programme at our unit. Thirty-seven patients (median age 69 years, 26 men) received conservative medical therapy (CMT) and 33 patients (median age 67 years, 22 men) received CMT plus a 3 month SEP of graduated physical exercise for sixty minutes, three times each week. Patients were assessed prior to and at 6 months following treatment. At each assessment patient reported walking distances (PRWD), treadmill claudication and maximal distances (ICD and MWD), ankle brachial pressure indices (ABPI) pre & post exercise and patient reported QoL using the SF36 questionnaire were assessed.
Results
Prior to intervention the two groups were well matched. Following treatment, CMT patients demonstrated no significant change in PRWD or ICD but did record a small but significant improvement in MWD. CMT was also associated with a negative effect size in the SF36 index and in 7 of the 8 SF36 QoL domains, effect size >−0.5 for the domains of Physical Function and Emotional Role. SEP patients demonstrated significant improvement in PRWD, ICD and MWD. SEP was associated with a positive effect size in the SF36 index and in 2 SF36 QoL domains but a negative effect size in a further 2 domains. However, all QoL effect sizes following SEP were < ±0.5. Intergroup differences in effect sizes were >0.5 for the SF36 domains of Physical Function, Physical Role, Emotion Role and SF36 index. SEP resulted in a 0.027 quality adjusted life year (QALY) gain over CMT in the first year post-treatment thus the cost/QALY gained of SEP is £1780 at 1 year.
Conclusions
Compared to CMT, SEP increases walking distances, improves QoL and is a highly cost-effective treatment for IC.
Keywords: Supervised exercise programme, Intermittent claudication, Quality of life, Cost effectiveness
Introduction
Peripheral arterial disease increases with age affecting 5% of the population aged ≥55 years, resulting in serious quality of life (QoL) limitations.1, 2 Current treatment of intermittent claudication (IC) is multimodal and variable. Risk factor modification should be mandatory as the major cause of mortality in patients with IC are cardiac and cerebral rather than peripheral arterial disease itself.3, 4, 5 Specific therapy for IC should aim to improve patients QoL in addition to the clinical indicators of lower limb ischaemia whilst providing value for money. Exercise is generally recommended for patients with IC who are advised to walk to and beyond their ischaemic pain. Supervised Exercise Programmes (SEP) for claudicants have been demonstrated to be beneficial in terms of improved walking distances but are not universally available.6, 7, 8 This may be due to the paucity of supportive QoL9 and health economic data. The aims of this study were to assess whether SEP for IC improves patients QoL and is cost effective.
Methodology
Patients
70 patients with intermittent claudication were recruited sequentially into the study from a vascular outpatient clinic setting. Patients were divided in recruitment into those recruited before and after the establishment of a Supervised Exercise Programme (SEP) at our unit. Thirty-seven patients (median age 69 years, 26 men) received Conservative Medical Therapy (CMT) as they were recruited prior to the establishment of our SEP. These patients were followed by 33 subjects (median age 67 years, 22 men) recruited during the early stages of the SEP. These later patients received CMT plus a 3 month Supervised Exercise Programme (SEP).
Intervention
Conservative medical therapyPatients undergoing CMT were prescribed an antiplatelet, received smoking cessation advice and support (including nicotine replacement therapy), and risk factor modification (appropriate management of hypertension, hypercholesterolaemia and diabetes according to evidence based care pathways within a dedicated clinic). All patients also received an advice leaflet regarding exercise.
Supervised exercise therapyIn addition to CMT, SEP patients attended three sessions of supervised exercise per week, for a total of twelve weeks. Each session consisted of alternating exercise stations of two minutes each, with walking circuits of two minutes in between exercise stations. The duration of exercise sessions was six stations for the first six weeks, increasing by one station per week thereafter. By end of the exercise programme, patients were completing twelve stations per session.
There were six exercise stations, arranged in the following order:
Station 1: Walking up and down a six-inch step.
Patients started with the left foot first, then changed the starting foot every ten steps. This was continued for two minutes.
Station 2: Double heel raise.
Standing erect, with both feet flat on the floor and holding hardrails for support, patients stood on tiptoes. This was held for approximately two seconds, then the patient slowly returned their weight to the floor. Repeated for two minutes.
Station 3: Single leg press.
Patients stood on one leg between two parallel bars, used for stability (but not weight-bearing). During the two-minute duration of this exercise, patients lowered their weight by bending at the standing leg, then straightened the leg against their own weight. After ten repetitions, the contralateral leg was exercised.
Station 4: Exercise bicycle.
The patients pedalled for two minutes on an exercise bicycle. Exercise resistance was sufficient to produce perspiration and dyspnoea, but still allowing conversation in complete sentences.
Station 5: Knee extension.
Patients sat on a high stool, knees flexed, with 2.5
kg weights attached to each ankle. One leg was slowly straightened to maximum extension, before being slowly returned to 90 degrees of flexion. Each leg was exercised in ten times in this manner, in alternating fashion for two minutes.
Station 6: Elbow flexion.
Whilst holding 1.5kg dumbbells, patients flexed and extended their elbows for 2 minutes.
Were performed prior to, and at 6 months following treatment. At each assessment, the following outcome measures were analysed.
Clinical indicators of lower limb ischaemia; Patient Reported Walking Distance (PRWD) was recorded. Patients were subjected to a standard treadmill walking test (2.4mph, 10 degree incline) to gauge treadmill Initial Claudication (ICD) and Maximal Walking Distances (MWD). Ankle Brachial Pressure Indices (ABPI) were recorded prior to and following treadmill testing.
Quality of life; was measured with the generic SF36 questionnaire. The SF36 produces a global index score and scores for 8 QoL domains: physical function (PF); role physical (RP); bodily pain (BP); vitality (Vit); social function (SF); mental health (MH); role emotional (RE) and general health (GH). Each domain is scored from 0 (worst health)–100 (best health) whilst the index is scored from 0 (worst health)–1 (best health). The validity, reliability and responsiveness of the SF36 in population studies and specifically in patients with lower limb ischaemia have been demonstrated.2
Cost effectiveness analysisThe SF36 index score was plotted over time for both groups of patients. Changes for 0 to 6 months were measured during the study and changes between 6 and 12 months were extrapolated. These extrapolations were based on previous studies using QoL outcomes in patients undergoing SEP.10, 11 Calculating the difference in Areas Under both Curves (AUC) gave the incremental QALY gain. Marginal costs to the NHS were obtained from the local NHS Hospital Trust finance department. Dividing the marginal cost per patient by the QALYs gained for SEP gave the cost/QALY value for SEP.
Statistical analysis
Standard testsData was entered into a spreadsheet (Microsoft Excel 95) and statistical analysis was performed using a commercially available statistics software package (SPSS version 11.5, SPSS Inc, Chicago, IL, U.S.A.). As the number of patients was small and data not normally distributed, non-parametric statistical tests were used. Clinical indicators of lower limb ischaemia were expressed as a medians±inter quartile range. Inter group analysis at baseline and at 6 months (Wilcoxon matched pair test) and intragroup analyis (Mann Whitney U test) comparing results pre and post treatment was performed. p values ≤ 0.05 were considered to be statistically significant.
QoL results are presented as effect sizes calculated by subtracting the pre treatment median from the post treatment median and dividing by the pre treatment interquartile range. An effect size±0.5 is considered to represent clinical significance. Effect sizes have been strongly recommended for interpretation of QoL changes in health care, in order to demonstrate the relative importance of a treatment effect within a study.12
Results
Patients (Table 1)
Patients groups were well-matched pre-treatment. The only significant difference in the clinical indicators of lower limb ischaemia between the two groups was in the initial patient reported walking distance. The only significant difference in SF36 domain/index scores were in the SF36 domains of BP and GH with higher scores in the SEP group.
Table 1. Effect of treatment on clinical indicators and SF36 QoL domains
| CMT | SEP | |||
|---|---|---|---|---|
| Pre | Post | Pre | Post | |
| Median age (range)/years | 69 (60.8–75.8) | 67 (61.0–72.8) | ||
| Men:Women | 26:11 | 22:11 | ||
| PRWD (metres) | 200 (100–600) | 225 (50–600) | 100 (50–300)+ | 600 (300–1200)∗+ |
| ICD (metres) | 78.4 (39.2–131.3) | 75 (45.0–180) | 58.5 (39.2–112.7) | 107.5 (52.5–153.8)∗+ |
| MWD (metres) | 152.2 (76.7–279.3) | 185 (102.0–300.0)∗ | 117.6 (73.5–205.8) | 300.0 (143.8–300.0)∗+ |
| ABPI – rest | 0.69 (0.56–0.84) | 0.77 (0.64–0.86) | 0.68 (0.55–0.89) | 0.71 (0.60–0.80) |
| ABPI – post exercise | 0.64 (0.51–0.81) | 0.57 (0.44–0.81) | 0.63 (0.44–0.81) | 0.64 (0.49–0.79) |
| SF36 PF | 52.5 (45.0–70.0) | 37.5 (11.3–63.8) | 45.0 (25.0–62.5) | 50.0 (35.0–67.5) |
| SF36 PR | 25.0 (0.0–100.0) | 0.0 (0.0–75.0) | 0.0 (0.0–75.0) | 25.0 (0.0–87.5) |
| SF36 BP | 31.0 (22.0–60.0) | 32.0 (22.0–52.0) | 52.0 (42.0–69.0)+ | 42.0 (31.0–52.0) |
| SF36 GH | 52.0 (40.0–60.0) | 47.5 (31.25–67.0) | 65.0 (52.0–72.0)+ | 60.0 (47.0–52.5) |
| SF36 Vit | 55.0 (40.0–62.0) | 45.0 (32.5–57.5) | 55.0 (50.0–70.0) | 55.0 (50.0–60.0)+ |
| SF36 SF | 53.8 (45.6–75.0) | 50.0 (43.8–65.0) | 50.0 (43.8–56.2) | 50.0 (40.0–52.5) |
| SF36 ER | 100.0 (8.3–100.0) | 50.0 (0.0–100.0)∗ | 66.7 (16.7–100.0) | 66.7 (16.7–100.0) |
| SF36 MH | 64.0 (56.0–75.0) | 60.0 (46.0–68.0)∗ | 64.0 (56.0–72.0) | 64.0 (56.0–72.0) |
| SF36 index | 0.615 (0.547–0.655) | 0.595 (0.547–0.650) | 0.600 (0.570–0.645) | 0.630 (0.570–0.650) |
∗p<0.05 intra-group analysis, Wilcoxon signed rank test. |
+p<0.01 inter-group analysis, Mann-Whitney U test. |
Clinical indicators of lower limb ischaemia (Table 1)
CMT patientsNo significant improvements were reported in PRWD, ICD, ABPI pre or post treadmill testing but there was a small but significant improvement in MWD.
SEP patients; demonstrated significant improvements in PRWD, ICD and MWD but no significant improvement in ABPI pre or post treadmill testing.
Intergroup analysis; The magnitude of improvement in PRWD, ICD and MWD following SEP exceeded that following CMT.
Short Form 36 results (Fig. 1)
CMT patients; demonstrated significant deterioration in the SF36 domains of ER and MH. CMT was also associated with a negative effect size in the SF36 index and in 7 of the 8 SF36 QoL domains, effect size >−0.5 for the domains of Physical Function and Emotional Role.
Fig. 1
Effects sizes for SF36 Domains and Index Score.
SEP patients; demonstrated no significant changes in the SF36 domains or index. Effect sizes following SEP were positive for the SF36 index and in 2 SF36 QoL domains (PF and RP) but negative in a further 2 domains (BP and GH). However, all QoL effect sizes following SEP were < ±0.5.
Intergroup analysis SF36 Vitality significantly improved following SEP compared to CMT. Intergroup differences in effect sizes were >0.5 for the SF36 index and the SF36 domains of Physical Function, Physical Role, Emotional Role.
Cost-effectiveness analysis (Fig. 2)
The area under each curve signifies total QALY for each patient group. The difference in area under the two curves denotes incremental QALYs gained. Plotting QALY curves for both groups of patients, then calculating the AUC between them gives an incremental gain of 0.027 QALYs gained in the first year. Costs for SEP were obtained from the Finance Department of the Hull Royal Infirmary. Three hours of supervised exercise per week for one year cost GBP2306.88. Each session can accommodate twelve patients, for three months, giving a minimum cost of GBP48.06 per patient, for a three-month SEP, assuming full recruitment. The cost/QALY for a 3 month SEP in the first year is GBP1780, given a gain of 0.027 QALY per year, at a cost of GBP48.06 per patient.
Fig. 2
QALYs gained. Shaded area represents QALYs gained. Therefore for first year, patient gains 0.027 QALYs (Areas A+B).
Discussion
In this era of evidence based care and limited resources, any interventions by necessity must be both clinically and cost effective. SEP for claudication improves walking distances, however the main treatment objective is to improve overall QoL. It cannot be assumed that improvements in the clinical indicators of lower limb ischaemia are mirrored by reciprocal QoL changes as it has been clearly demonstrated that correlation between the two is relatively poor. QoL improvements therefore cannot be inferred and must be actually documented. The impact of SEP on QoL in claudicants with appropriate controls has not been previously studied. Previous studies have analysed the impact of SEP on symptoms and walking distances but not QoL,13 and the impact of unsupervised exercise on QoL.10 Ours is the first study to demonstrate SEP for claudication is associated with, marked improvement in walking distances, modest improvements in physical QoL domains and prevention of the deterioration in the psychological QoL domains associated with CMT. The fall in bodily pain (signifying greater pain burden) with SEP, although not attaining statistical or clinical significance, we found interesting. This may signify patients following SEP are more willing to walk further with pain perhaps being reassured by SEP participation. More marked changes in QoL may have been demonstrated if we had used a disease specific rather than generic QoL instrument, which are generally accepted to be more sensitive to change. Health economic evaluation, however is currently only possible with generic instruments. In addition in the future we hope to compare the clinical & cost effectiveness of SEP for claudication with other interventions for common, non vascular, conditions.
The changes in the SF36 index for the first 6 months were measured, whereas the changes in the second six months were hypothesised using best available data. Previous SEP studies, several with more prolonged follow up, essentially demonstrate the benefits seen at 6 months in clinical indicators and QoL, persist but diminish.7, 9, 10, 11, 13 The specific rate of QoL deterioration following SEP cessation varies between studies. We have assumed QoL following cessation of SEP deteriorates at the same rate as in CMT patients. If the rate of decline was slower following SEP cessation this would further increase the incremental QoL gain and cost-effectiveness of SEP.
National Institute for Clinical Excellence (NICE) guidelines for best practice in the United Kingdom, with respect to cost per QALY gained, states that in order for a treatment to be regarded as cost-effective, the cost must fall to below GBP30000.00 per QALY gained. We can therefore claim SEP for claudication is highly cost effective.
Our sample of patients was recruited sequentially, although there were minimal differences between the two groups of patients, we would recommend randomised controlled studies in the future. In addition prolonged, multiple follow up points are suggested.
There are no existing trials examining the question of re-treatment with SEP. Patients who have previously benefited from SEP may benefit from a repeat SEP. This requires further investigation. In conclusion, SEP in patients with intermittent claudication improves the clinical indicators of lower limb ischaemia, improves physical QoL domains & prevents deterioration in psychological QoL. Health economic analysis demonstrates SEP is an extremely cost-effective treatment for claudication. We are currently recruiting into a randomized controlled trial with calculated sample sizes and longer follow-up periods. The effects of repeat or ‘booster’ SEP treatments also need to be explored.
Acknowledgments
The authors wish to thank Ms. Josie Hatfield, for data entry and management in all parts of the study and for assisting with patient follow-up.
References
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PII: S1078-5884(06)00497-7
doi:10.1016/j.ejvs.2006.08.005
© 2006 Elsevier Ltd. All rights reserved.
Volume 33, Issue 2 , Pages 202-207, February 2007
