The Oslo Balloon Angioplasty versus Conservative Treatment Study (OBACT)—The 2-years Results of a Single Centre, Prospective, Randomised Study in Patients with Intermittent Claudication

Eur J Vasc Endovasc Surg 33, 3e12 (2007) doi:10.1016/j.ejvs.2006.08.007, available online at http://www.sciencedirect.com on

The Oslo Balloon Angioplasty versus Conservative Treatment Study (OBACT)dThe 2-years Results of a Single Centre, Prospective, Randomised Study in Patients with Intermittent Claudication M. Nylænde,1* M. Abdelnoor,2 E. Stranden,3 B. Morken,3 G. Sandbæk,4 Ø. Risum,1 J.J. Jørgensen,1 A.K. Lindahl,1 H. Arnesen,2,5 I. Seljeflot2 and A.J. Kroese1 1

2

Department of Vascular Surgery, Aker University Hospital, Norway, Center for Clinical Research, Ulleva˚l University Hospital, University of Oslo, Norway, 3 Department of Vascular Diagnosis and Research, Aker University Hospital, Norway, 4 Department of Radiology, Aker University Hospital, Norway, and 5 Department of Cardiology, Ulleva˚l University Hospital, University of Oslo, Norway

Objectives. To compare the effect of optimal medical treatment only (OMT) with OMT combined with percutaneous transluminal angioplasty (OMT þ PTA) in patients with intermittent claudication (IC). Design. A single centre prospective, randomised study. Quality of life (QoL) was the primary outcome measure. Secondary measures were ankle-brachial-index (ABI), treadmill walking distances and mortality. Methods. From a total of 434 patients considered for inclusion into the trial, only 56 patients with disabling IC fulfilled the inclusion criteria. The patients were randomised into treatment groups consisting of 28 patients each and followed for 2 years. ABI and treadmill walking distances were measured in addition to the visual analogue scale (VAS) for pain evaluation, and QoL assessment using the Short Form (SF-36 and Claudication Scale (CLAU-S). Results. The demographic data in the 2 groups were almost identical. After 2 years of follow-up the ABI, the treadmill walking distances and the VAS were significant improved in the group treated with OMT þ PTA, compared to the group treated with OMT only (p < 0.01 for all). Furthermore, some variables from the QoL assessment also showed a significant improvement in favour of the OMT þ PTA group (p < 0.05 for all). Conclusion. The advantage of conducting a single centre study and adhering to very strict inclusion criteria was illustrated by the homogenous demographic data of the two groups. This partly outweighed the disadvantage of having included a relatively small number of patients. Early intervention with PTA in addition to OMT seems to have a generally more positive effect compared to OMT only, on haemodynamic, functional as well as QoL aspects during the first 2 years in patients with IC. Keywords: Optimal medical treatment (OMT); Percutaneous transluminal angioplasty (PTA); Exercise training; Quality of life (QoL); Treadmill walking distance.

Introduction Peripheral arterial occlusive disease (PAD) causing intermittent claudication (IC) affects approximately 5% of the elderly population over 55 years.1 Local progression of disease occurs in approximately 25% and about 1.6% end up with amputation.2,3 Annual mortality rate in these patients is as high as 5e10%, mainly caused by myocardial infarction and stroke.3,4 * Corresponding author. M. Nylænde, Department of Vascular Surgery, Aker University Hospital, Huk Aveny 5b, NO-0287 Oslo, Norway. E-mail address: [email protected]

There is still no cure for PAD. Hence, all treatment of patients with IC should be minimally invasive and aimed primarily at alleviating symptoms, eliminating risk factors, and improving quality of life (QoL).5e9 First and foremost this is achieved by optimal medical treatment (OMT), including patient education with regard to exercise, nutrition and smoking cessation. Medication include antiplatelet drugs as well as lipid-lowering agents, antihypertensives, and antidiabetic agents, when indicated.8,10e12 Percutaneous transluminal angioplasty (PTA) has been popularised as a simple and effective treatment with 5 year patency rates of 50e80%.13 It has been estimated that approximately 40% of patients with IC

1078–5884/000003 + 10 $32.00/0 Ó 2006 Elsevier Ltd. All rights reserved.

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M. Nylænde et al.

have arterial lesions amenable to PTA.14 As a result, a large number of PTAs have been performed world wide. The effectiveness of OMT compared to PTA has not yet been established, and it is still unclear whether early intervention with PTA improves the QoL in these patients. Only 2 prospective, randomised trials comparing the effect of exercise training with PTA, conducted in Oxford15,16 and in Edinburgh,16,18 respectively, fulfilled the criteria of the Cochrane Review Group. However, these trials have also been criticised for having several flaws, resulting in inconclusive findings.19 The aim of this single centre, prospective, randomised study was to investigate whether patients with IC are best treated with OMT only, or in combination with PTA. The primary outcome measure was QoL. Secondary outcomes were ankle-brachialindex (ABI), treadmill walking distances and mortality, evaluated after 3, 12 and 24 months.

Patient Screening (Fig. 1) One surgeon only was responsible for the screening process to secure optimal standardisation and adherence to strict inclusion- and exclusion criteria. Inclusion criteria:  <80 years of age  Symptomatic IC > 3 months  ABI < 0.9 without pain at rest and/or ischemic skin changes  A lesion feasible for angioplasty evaluated by angiography  Subjective painfree walking distance (PFWD) < 400 m  Able to exercise on a treadmill Exclusion criteria: Previous vascular or endovascular surgery  Diabetic skin ulceration  Renal insufficiency (defined as serum creatinine >150 mmol/L)  Oral anticoagulant medication, in order to minimise the number of factors influencing the outcome of treatment  Suffering from a physical or mental disorder expecting to impede compliance 

During the 2-year inclusion period, 826 patients were referred to the Oslo Centre of Vascular Surgery, Aker University Hospital, Norway, with IC as tentative diagnosis. Based on the written information from the referring general practitioners, only 434 Eur J Vasc Endovasc Surg Vol 33, January 2007

Fig. 1. Flowchart of the patient selection from primary referrals to randomisation and inclusion in the study.

patients were invited to a consultation at our Outpatient Department. The patient’s history was recorded and a thorough clinical examination was performed, including measurement of Doppler ABI, body-massindex (BMI) and CO-content in expired air. The Visual Analogue Scale (VAS) was used to assess the patient’s subjective maximum claudication pain. Furthermore, information for the QoL questionnaires (Short Form (SF-36) and Claudication Scale (CLAU-S)) was recorded. In this process 287 patients were excluded, 143 because of an incorrect clinical diagnosis by the referring physicians (Fig. 1). Thus, the remaining 147 patients underwent treadmill testing in order to get an objective measure of their painfree- and maximum walking distance (PFWD and MWD, respectively). The treadmill test was performed twice. The first test was chosen to familiarise the patients with the treadmill. The second test was used in subsequent analyses, and was performed later in the screening programme. At this stage 16 patients were excluded, of whom 12 failed to exercise on the treadmill because of shortness of breath or feeling uncomfortable, 1 patient died at home, and 3 refused to participate in the study. Altogether, 131 patients managed to exercise on the treadmill and were still willing to participate in the

5

The 2-years Result of the OBACT-study

study. They were hospitalised for 2 days for a final screening. Fasting blood samples were drawn, and the patients underwent their second test on the treadmill. In addition, all patients had a consultation with a clinical nutritionist. Finally, the precise extent and localisation of peripheral limb atherosclerosis was assessed by angiography. Only patients with a lesion feasible for PTA were included. At this stage another 75 patients were excluded for various reasons: 59 patients had lesions not amenable for PTA, 3 had developed diabetic ulcers, 2 had died and 11 were no longer compliant (Fig. 1). Finally, 56 patients could be included in the study. Randomisation was performed in accordance with a computerised randomisation list by use of consecutively numbered sealed envelopes. Twenty-eight patients were randomised to OMT and another 28 to OMT þ PTA. Thus, the latter group was treated with an additional angioplasty. The patients were followed up for 2 years. Approval was given from the Regional Ethical Committee, and all patients gave their written, informed consent to participate. Patient follow-up All patients were followed up at 3, 12 and 24 months. Evaluation encompassed: ABI, PFWD, MWD, BMI, fasting blood chemistry, VAS assessment, and the completion of the 2 QoL questionnaires. Smoking habits were objectively evaluated by CO-measurements in expired air. Compliance on exercise, nutrition and medication were registered. The patients also had a consultation with a clinical nutritionist twice during the 2 years of follow-up. Only 2 surgeons were involved in the clinical and organisational part of the follow-up program to secure a best possible compliance and conformity of all procedures involved. Methods ABI measurement After a 5 min rest period in the supine position, a hand-held Doppler probe (Parks model 811, Parks Medical Electronics Inc, Aloha, OR, USA), and a 13 cm wide pneumatic cuff were used to measure systolic blood pressures in the brachial artery, the anterior tibial artery and the posterior tibial artery in both limbs.20 The highest mean of two consecutive ankle pressure measurements in each artery was used to calculate ABI. The ABI obtained from the patient’s primary symptomatic side was used for

subsequent analysis. In the cases where the 2 sides were symptomatically indiscriminate from one another, the right leg was referred to as the primary symptomatic leg. Treadmill A standard treadmill test (Treadmill Proform, Icon Health & Fitness, Logan, USA) with a constant speed of 3 km/h and a fixed grade of 10 was chosen. PFWD and MWD were recorded. Walking was continued up to a maximum of 600 m, (12 min, alternatively), although some patients were able to walk further. In these cases, the MWD was equaled to 600 m. Angiographic score (Fig. 2) All included patients underwent digital subtraction angiography (DSA). We chose an angiographic scoring system reflecting the over-all anatomical severity of PAD.21 This would allow us to compare it with the functional severity of PAD, as reflected by ABI, treadmill walking distances and QoL findings. The following arterial segments (distal aorta plus 10 segments on each side) were assessed: common iliac artery, external iliac artery, common femoral artery, profunda femoral artery, superficial femoral artery, popliteal artery, tibio-peroneal trunk, anterior tibial artery, posterior tibial artery and peroneal artery. A score was given to the area with the greatest narrowing in each segment. The following scores were used: 0 ¼ normal, 1 ¼ stenosis < 50% (luminal irregularities, insignificant stenosis), 2 ¼ stenosis  50% (significant stenosis), 3 ¼ occlusion. The different scores for each of the 21 segments were then added up to give the angiographic score for each patient, 63 being the maximal score. Visual analogue scale (VAS) The VAS is frequently used to assess a patient’s perception of pain, on which the patients rate their own health between 0 and 10.22 The patients were asked to rate their perception of leg pain in their primary symptomatic leg just before they had to stop when walking. Quality of life assessment The patients were asked to complete 2 questionnaires assessing QoL. They were given the opportunity to ask for assistance whenever necessary. Eur J Vasc Endovasc Surg Vol 33, January 2007

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disease-specific anxiety and mood.25 Each domain was transformed into a 0e10 scale.

Optimal medical treatment (OMT)

Fig. 2. Schematic outline of the lower extremity arteries; da: distal aorta, ci: common iliac artery, ei: external iliac artery, cf: common femoral artery, pr: profunda femoral artery, sf: superficial femoral artery, p: popliteal artery, tpt: tibial peroneal trunk, at: anterior tibial artery, pt: posterior tibial artery, f: fibular artery.

The SF-36 questionnaire is a generic instrument comprising 36 items and providing scores for 9 distinct domains: physical functioning (PF), social functioning (SF), vitality (V), role limitations due to physical (RP) and emotional (RE) problems, mental health (MH), bodily pain (BP), general health perception (HP) and reported health transition (HT) rendering a profile of health. Each domain was transformed into a 0e10 scale. The SF-36 is a useful and widely used QoL instrument in patients with PAD.23,24 The CLAU-S has until recently been the most extensively researched disease specific QoL questionnaire for patients with IC. The questions are grouped into 5 domains, including 7 specific subgroups, which each get a score: daily living, pain, social life, Eur J Vasc Endovasc Surg Vol 33, January 2007

Since we still are not sure what the term ‘‘best medical treatment’’ encompasses, we opted for the expression of OMT, indicating a treatment based upon recent information from the literature combined with the best of our own resources to coach these patients. All patients were thoroughly informed about how to reduce the various risk factors for developing atherosclerosis.5,6,10 Smokers were offered the use of nicotine plaster and prescribed ZybanÒ (bupropionhydrocloride), if not contraindicated.26,27 Exercise training has been proven to have a positive impact on IC and QoL.28 Our patients were offered a home-based program, as it reflects the everyday life to a larger degree than centre-based programs.29 They were informed about the importance of walking and were explained how to organise their own private exercise program by walking along the same path twice a day and trying to steadily increase MWD. Individual nutritional advice was given by a clinical nutritionist at the time of randomisation and twice during the follow-up period. A Mediterranean type diet, rich in fruits, nuts, vegetables, fish, polyunsaturated fatty acids and fibres was emphasised.30 Acetylsalicylic acid, 160 mg, daily, was prescribed to all patients. The prophylactic effect of aspirin in patients with PAD, especially with regard to the prevention of stroke and myocardial infarction, is well documented.31 Patients with a previous history of peptic ulcer received PlavixÒ (clopidogrel). Patients with untreated hypercholesterolaemia (defined as s-total cholesterol > 5 mmol/L and/or s-LDLcholesterol > 3 mmol/L) had statins prescribed.32,33 According to general rules in Norway, the cheapest generic medicine is prescribed preferably. Patients already using a certain statin on admission to the study were permitted to continue with the particular agent they used. There is yet no convincing evidence that treatment of hypertension reduces the progression of PAD, but the association between hypertension and cerebral stroke and myocardial infarction has been well documented.34 Hypertension is often defined as a systolic blood pressure > 140 mmHg and/or diastolic pressure > 90 mmHg.35 The treatment was individualised in co-operation with the patient’s general practitioner, based on relevant literature and generally accepted practice.

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The 2-years Result of the OBACT-study

Endovascular treatment (PTA) To measure the severity of stenosis the luminal diameter at the site of narrowing was compared with the vessel above and below the lesion.36 Lesions considered feasible for PTA were >50% stenoses or occlusions of a length <8 cm. A balloon was chosen with approximately the same diameter as the adjacent normal appearing artery. In multi-level disease, both iliac and infra-inguinal lesions were treated. Peak systolic measurements were performed following iliac angioplasty. Angioplasty was considered to be successful if the residual stenosis was < 30% and antegrade flow was established. Iliac occlusions were treated with primary stenting. Iliac stenoses were selectively stented if the result after PTA seemed unsatisfactory: residual stenosis  30% or sluggish blood flow due to dissection or residual pressure gradient  10 mm Hg. The appropriateness of this approach has been recently documented.37 Stents were not used infra-inguinally. Although there have been some reports on the beneficial use of stents/stent grafts in the superficial femoral arteries, our own experience does not confirm these results, neither does the majority of previous publications.38 At the beginning of the procedure, patients were given 5000 units of heparin intra-arterially.

Epidemiological and statistical considerations The power estimation was based on the end-point QoL under the following assumptions: We estimated the improvement in the QoL in OMT group at 2 years to be 20%. For group OMT þ PTA we estimated that the improvement in QoL would be 40%. For a type-I error of 5% and a power of 80% we would need approximately 100 patients in each group, thus a total of 200 patients. The results of the QoL questionnaires were analysed by using Epi InfoÔ software version 3.3.2. The other results were analysed using SPSS software package for Windows, version 12.0.1 (SPSS INC, Chicago, Illinois, US). For group comparison of continuous variables the Student’s t test was used when the distribution was Gaussian with homogeneity of variance. If not, the non-parametric Mann-Whitney test was used. Categorical variables were assessed using the Chisquare tables. When one of the expected values in the cell was <5 under the null-hypothesis, the Yate’s correction or the Fisher exact test was applied.

To compare the changes between the 2 groups from baseline to the end of a treatment period, we used the Mann-Whitney test.

Results Baseline data Baseline demographic and laboratory data are presented in Table 1. Statistical analysis revealed no significant difference between the 2 patient groups for any of the recorded variables, except for antiplatelet medication ( p ¼ 0.022) before inclusion in the study. The included patients had suffered from IC for a median period of 14.5 months before inclusion, Table 1. Demographic and laboratory data for groups OMT and OMT D PTA. Proportions or median values (25, 75 percentiles) are given

Male n (%) Age (years) SBP mmHg DBP mmHg Unilateral symptoms n (%) Duration of symptoms of IC (months) ABI symptomatic leg ABI contralateral leg Angiographic score (0e63) VAS score PFWD on treadmill (0e600 m) MWD on treadmill (0e600 m) Subjective PFWD (m) Subjective MWD (m) Treated hypertension n (%) Treatment with antiplateletsa,b n (%) Treated hypercholesterolemia n (%) Untreated hypercholesterolemia n (%) Diabetes mellitus (Type I and II) n (%) COLD n (%) CHD n (%) Smokers (current/previous) n (%) Smoking years BMI kg/m2 s-LDL mmol/L s-HDL mmol/L s-Total Cholesterol mmol/L s-triglycerides mmol/L b-HbA1c % s-glucose mmol/L

OMT (n ¼ 28)

OMT þ PTA (n ¼ 28)

15 69 153 80 18 12

(54) (61,75) (140,170) (70,85) (64) (5,48)

16 68 153 80 17 17

(57) (56,72) (136,170) (74,85) (61) (6,36)

0.65 0.93 13 6.2 47 224 150 325

(0.52,0.74) (0.78,1.12) (10,23) (5.0,7.5) (33,81) (137,517) (50,275) (200,475)

0.63 0.93 13 6.4 62 190 150 300

(0.56,0.71) (0.77,1.02) (6,18) (5.0,7.4) (35,83) (101,591) (100,200) (200,600)

15 (54) 13 (46)

8 (29) 5 (18)

6 (21)

8 (29)

20 (71)

16 (57)

6 (21)

4 (14)

2 (7) 5 (18) 19 (68)/8 (29)

2 (7) 2 (7) 20 (71)/6 (21)

42 (36,50)

42 (33,50)

25 3.7 1.36 5.6 1.3 6.2 5.7

(23,26) (3.2,4.5) (1.12,1.68) (5.0,6.5) (0.93,1.60) (5.6,6.7) (5.3,6.9)

26 3.4 1.35 5.7 1.5 6.0 5.7

(23,28) (2.7,4.2) (1.16,1.58) (4.9,6.4) (1.1,1.9) (5.8,6.3) (5.2,6.1)

SBP: systolic brachial pressure, DBP: diastolic brachial pressure, COLD: chronic obstructive lung disease, BMI: body-mass-index, CHD: coronary heart disease. For other abbreviations: see text. a aspirin or clopidogrel. b p ¼ 0.022 for difference between groups. Eur J Vasc Endovasc Surg Vol 33, January 2007

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and their median perception of claudication pain as assessed by VAS was 6.3. Seventy % of the patients were current smokers, 25% had smoked previously, and only 5% had never been smokers. Sixty-four % had untreated hypercholesterolaemia, and 18% had diabetes mellitus. Coronary heart disease was defined as a known previous myocardial infarction and/or angina pectoris and was recorded in 13% of the patients. Details on location of main obstructions and limb involvement are shown in Table 2. There were no significant group differences. The angioplasty was technically successful in all 28 cases in group OMT þ PTA. No significant complications were encountered, such as bleeding, local thrombosis, emboli, local arterial dissection or perforation. A few patients had a small haematoma in the groin, but none was in need of surgical revision. Statistical analysis revealed no significant differences between the recorded QoL-measurements between the 2 groups at baseline. Results at follow-up Compliance to attendance was practically identical in the 2 groups (Table 3). The numbers of patients who died or were lost during the follow-up period were not significantly different between the 2 groups. Two patients crossed-over from the OMT to the OMT þ PTA group, and were thus treated with PTA. There was no difference in compliance to OMT between the 2 groups with regard to smoking cessation, exercise training, diet, or use of medication such as statins, antiplatelets, antihypertensives and antidiabetic agents. No group differences were recorded in ABI at baseline. After 24 months ABI in group OMT remained unchanged, whereas it had increased significantly after 3 months and was sustained throughout the study in the OMT þ PTA group (Table 4). The differences in change between the two groups were highly statistically significant ( p < 0.001 for all). At the beginning of the study PFWD and MWD were not different between the groups (Table 4). After Table 2. Angiographical peripheral arterial obstruction. Location and limb involvement. Proportions are given Site

Total population (n ¼ 56) Unilateral

Bilateral

Aortoiliac n (%) Femoropopliteal n (%) Combined n (%) Total n (%)

1 (1.8) 0 0 1 (1.8)

9 1 45 55

Eur J Vasc Endovasc Surg Vol 33, January 2007

(16.1) (1.8) (80.4) (98.2)

Table 3. Compliance to attendance for group 1: OMT and group 2: OMT D PTA Number of patients included

Group

Number of patients

Lost to follow-up

1 2 1 2 1 2

4 1 2 0 0 1

Cross-over Dead Patients at end of study

56 5 2 1 48

3, 12 and 24 months, these variables had increased significantly in both groups, though significantly more in the OMT þ PTA group, compared to the OMT group ( p < 0.05 for all). After 3 months the VAS-score was significantly more reduced in the OMT þ PTA group, compared to the OMT group ( p < 0.0001) (Table 4). This positive effect lasted almost unchanged during the whole follow-up period. In the OMT alone group the VASscore also decreased significantly over time. We obtained information from 9 domains of the SF-36 and compared the results of the 2 groups at the start of the study and after 3, 12 and 24 months (Table 5). The measured differences in changes from baseline were statistically significant in favour of the OMT þ PTA group. The greatest difference between the groups was obtained after 3 months in the domains of physical functioning ( p ¼ 0.0003), bodily pain ( p < 0.014), and reported health transition ( p < 0.0001). Only with regard to physical functioning did this positive effect last for 2 years ( p < 0.0098). Within both groups the reported health transition were improved at 12 and 24 weeks ( p < 0.001 for all). The most noticeable differences in QoL between the groups were shown in the results from the CLAU-S form (Table 6). In 2 of the 7 domains, pain during activity and pain severity, respectively, the group OMT þ PTA had improved significantly at 3 and 12 months, compared to the OMT group ( p < 0.05) (Table 6). However, after 2 years no differences between groups were recorded.

Discussion Life-style modification and relevant medication is still the cornerstone in treating patients with PAD.39 However, millions of PTAs have been performed world-wide, without its potential additive effect having been fully evaluated. The research question for the OBACT study was whether OMT only or in combination with early PTA is the best treatment for patients with IC. We opted for a single centre study to obtain the best

Group 1: OMT. Group 2: OMT þ PTA. NS: Not significant. The numbers represent mean, standard deviation and p-values for inter-group difference in changes. *p < 0.05, **p < 0.001, ***p < 0.0001 represent intra-group changes from baseline. For abbreviations see text.

p ¼ 0.0008 3.7 (2.6)** 1.3 (2.1)*** 6.1 (2.1)** 1.9 (2.3)*** 1 2 VAS (0e10)

7.4 (1.9) 7.2 (1.5)

p ¼ 0.4356

p < 0.0001

5.8 (6.6) 1.2 (2.0)***

p < 0.0001

p ¼ 0.0009 319.5 (220.4)*** 539.2 (144.3)*** 303.4 (202.0)*** 427.3 (207.3)*** 1 2 MWD

265.4 (173.5) 323.9 (231.5)

p ¼ 0.7406

p ¼ 0.0258

298.0 (232.5)*** 495.1 (204.1)***

p ¼ 0.0066

p ¼ 0.0001 174.9 (171.8)*** 435.0 (223.8)*** p ¼ 0.0001 96.6 (99.1)* 316.5 (249.4)*** 1 2 PFWD

69.6 (54.2) 93.5 (72.9)

p ¼ 0.1213

p ¼ 0.0004

123.0 (131.3)* 398.5 (244.8)***

0.73 (0.04) 0.93 (0.05) 0.73 (0.02) 0.93 (0.02)*

24 months 3 months

0.68 (0.01) 0.92 (0.03)*** 0.65 (0.01) 0.63 (0.01)

Baseline Group

1 2 ABI

Table 4. Clinical results

p ¼ 0.3499

p < 0.0001

12 months

p < 0.0001

p ¼ 0.0013

The 2-years Result of the OBACT-study

9

possible homogenicity with regard to the selection and guidance of the patients and follow-up. The primary end-point was QoL because all treatment of patients with IC focuses on increasing QoL, as well as preventing death caused by myocardial infarction or stroke. IC can be very disabling as patients are prohibited from carrying out their daily activities. Thus, health-related QoL scores are reportedly much lower in patients with IC than in age-matched groups without clinical symptoms of PAD.40

Screening/selection of patients It was interesting to note that 33% of the referred patients had symptoms incorrectly diagnosed as IC. In addition, 6% of the patients had developed critical ischemia by the time they were examined at the Outpatients’ clinic. These findings made us distribute up-dated information to general practitioners on how to examine, treat and refer patients with PAD. Sixteen patients were excluded because they did not manage to walk on the treadmill. They were elderly, had difficulties with keeping their balance or complained of shortness of breath. Forty-five % of the patients had to be excluded because the arterial lesions were not amenable for PTA. This finding agrees with our own previous experience as well as the experience of other centres.41 Although the Oxford and Edinburgh studies had less strict inclusion/exclusion criteria than our study, they experienced similar problems in including patients.15e18 Thus, neither the Edinburgh, nor the Oxford study had an upper age limit for participation. The Oxford study accepted patients earlier treated with endovascular and/or vascular surgery and taking oral anticoagulants. Furthermore, the Edinburgh study included patients with duration of symptomatic IC > 1 month, whereas the Oxford study had a minimum duration of symptomatic IC of 3 months, similar to the OBACT study. It may seem controversial that we only included patients with a subjective PWD <400 m. However, this reflects the everyday vascular practice in Norway. All patients with IC primarily undergo a 4e6 months standard regimen of OMT, and after this period they are evaluated for a possible PTA. The strict entry criteria while limited the numbers of patients included did result in homogenous groups of patients with good compliance to the follow-up (Table 3). It should also be emphasized that the results presented have been obtained in patients with PFWD <400 m and angiographically verification of lesion (s) feasible for PTA. The results are therefore not easily Eur J Vasc Endovasc Surg Vol 33, January 2007

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Table 5. Results of the SF-36 questionnaire Subgroups

Treatment

Baseline

3 months

Physical functioning

1 2

NS

0.33 (0.12)* 0.16 (0.02)***

12 months

Physical role

1 2

NS

Bodily pain

1 2

NS

General health

1 2

NS

Vitality

1 2

Social functioning

24 months

p ¼ 0.0003

NS

NS

NS

NS

NS

NS

NS

NS

NS

NS

NS

NS

NS

1 2

NS

NS

NS

NS

Role emotional

1 2

NS

NS

NS

Mental health

1 2

NS

NS

NS

Reported health transition

1 2

NS

p ¼ 0.014

0.03 (0.25) 0.07 (0.20)

0.16 (0.50) 0.60 (0.26)***

p < 0.0001

*** ***

** ***

NS

0.11 (0.32) 0.06 (0.26)

0.15 (0.33) 0.02 (0.34)

p ¼ 0.0098

p ¼ 0.0372 NS

*** ***

NS

Group 1: OMT. Group 2: OMT þ PTA. NS: Not significant. Mean and standard deviation is calculated as difference of score between actual month and start of study. P-values represent inter-group difference in changes. *p < 0.05, **p < 0.001, ***p < 0.0001 represent intra-group changes from baseline.

generalized to the common IC patient in everyday practise. Baseline data Angiography is still considered the gold standard in presenting anatomical information of the arteries, whereas ABI represents the physiology. The patients’ perception of maximum walking pain, determined

by the VAS, shows median values of 6.2 and 6.4 for group OMT and group OMT þ PTA, respectively. This finding is in accordance with the fact that these patients experienced pain when walking at the time of the inclusion. The primary technical results of PTA where similar to those from the literature, where more than 90% of femoral stenoses and short occlusions can be successfully dilated in experienced hands.42

Table 6. Results of CLAU-S questionnaire Subgroups

Treatment

Baseline

Every day life

1 2

NS

Pain during activity

1 2

NS

Severity of pain

1 2

NS

Pain related to sleep

1 2

NS

Social life

1 2

Specific fears rel. to illness Psychological well-being

3 months

12 months

24 months

NS

0.01 (0.25) 0.12 (0.17)

p ¼ 0.0334

0.04 (0.17) 0.20 (0.19)***

p ¼ 0.0014

0.06 (0.28) 0.19 (0.21)***

p ¼ 0.0381

0.03 (0.09) 0.10 (0.08)***

p ¼ 0.0010

0.16 (0.24)** 0.02 (þ0.22)

p ¼ 0.0085

NS

NS

NS

NS

NS

NS

NS

NS

1 2

NS

NS

NS

NS

1 2

NS

NS

NS

NS

NS * ***

NS

Group 1: OMT. Group 2: OMT þ PTA. NS: Not significant. Mean and standard deviation is calculated as difference of score between actual month and baseline. P-values represent inter-group difference in changes. *p < 0.05 represents intra-group changes from baseline. Eur J Vasc Endovasc Surg Vol 33, January 2007

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The 2-years Result of the OBACT-study

Intervention results Physical and functioning measurements It was not surprising that ABI increased immediately after PTA, but we did not expect this result to be maintained for as long as 2 years. The benefit of PTA, expressed by the ABI findings, is definitely more significant in our study compared to the Oxford and Edinburgh studies,15e18 possibly due to our strict inclusion/exclusion criteria and the much standardised follow-up programme. The improvement of PFWD as well as MWD in both groups clearly illustrates the advantage of intervention with OMT, which was received by both groups, although the increase in treadmill walking distances was significantly larger in the OMT þ PTA group. The significant additional effect of PTA on the patient’s walking ability appeared after 3 months, as might be expected, and lasted for at least 2 years. Regarding the VAS-score, the beneficial effect of performing additional PTA was very convincing, and the effect lasted almost unchanged during the 2 years. The patients in the OMT group never achieved the improvement seen with the OMT þ PTA group. This supports the results from a recent study comparing the effect of exercise training with PTA.43 Even though the ABI, the treadmill walking distances and the VAS were improved in favour of the OMT þ PTA group during the 2 years of follow-up, significant improvement over time was also obtained in the OMT only group. This demonstrates that OMT in itself is a beneficial treatment option for patients suffering from IC, and whose arterial lesions are not amenable for PTA. QoL-measurements The information from the SF-36 evaluation, does not allow us to make definite conclusions on the effect of OMT versus OMT þ PTA on the QoL in patients with IC. The results have to be interpreted with caution as the number of patients entered was significantly less than required in the power calculation. However, the significant differences reflected in 3 of the 9 domains, physical functioning, bodily pain and reported general health, respectively, were all in favour of the OMT þ PTA group. This positive effect started early, which is in accordance with the findings of early improvement of ABI and treadmill walking distances in these patients. The most obvious differences in QoL between the groups were obtained from the CLAU-S forms. In 2 of the 7 domains, pain during activity and pain severity, respectively, the OMT þ PTA group did

significantly better after 3 and 12 months, compared to the OMT group. However, these differences were not sustained at 2 years. It has been stated that the generic SF-36 assessment is too little disease specific. Nevertheless, a recent prospective (but non-randomised) study comparing the effect of PTA (47 patients) with OMT (23 patients), also showed the very beneficial effect of PTA with regard to ABI, treadmill walking distances, VAS and QoL.24 The authors of this study, comparing different forms of QoL assessment, concluded that future research analysing QoL in claudicants should include the generic SF-36 and the recently developed diseasespecific VascuQol.24 In our primary power estimation we used 20% difference in change of QoL between the 2 arms of the trial after 2 years, which means 100 patients in each arm were required. Unfortunately, fewer patients than expected were included. The inclusion was stopped after 2 years, even though we had only managed to include 56 of the 200 patients required for the evaluation of QoL, the study’s primary end-point. We realized that in order to include 200 patients we would probably need to include patients for another 6e8 years. To evaluate the secondary end-points of the study, however, the number obtained was estimated to be sufficient. Hence, our study seems to have enough power with regard to the the evaluation of the ABI, the treadmill walking distances and the VAS. In conclusion, our findings support a benefit of PTA in improving outcome for IC. Our secondary endpoints, ABI, treadmill walking distances and VAS all definitely confirm the beneficial effect of performing PTA, sustaining for at least 2 years.

Acknowledgements We thank Irma Arnesen, Department of Vascular Surgery for superb logistics and secretary work, and The Medical Department of Day-Treatment, Aker University Hospital for excellent co-operation and patient handling. The study was supported with unrestricted grants from Pfizer AS, Norway.

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Accepted 27 August 2006 Available online 20 October 2006