Safety of urgent endarterectomy in acute non-disabling stroke patients with symptomatic carotid artery stenosis: an international multicenter study.

BACKGROUND AND PURPOSE: International recommendations advocate that carotid endarterectomy (CEA) should be performed within 2 weeks from the index event in symptomatic carotid artery stenosis (sCAS) patients. However, there are controversial data regarding the safety of CEA performed during the first 2 days of ictus. The aim of this international, multicenter study was to prospectively evaluate the safety of urgent (0-2 days) in comparison to early (3-14 days) CEA in patients with sCAS. METHODS: Consecutive patients with non-disabling (modified Rankin Scale scores ≤2) acute ischaemic stroke or transient ischaemic attack due to sCAS (≥70%) underwent urgent or early CEA at five tertiary-care stroke centers during a 6-year period. The primary outcome events included stroke, myocardial infarction or death during the 30-day follow-up period. RESULTS: A total of 311 patients with sCAS underwent urgent (n = 63) or early (n = 248) CEA. The two groups did not differ in baseline characteristics with the exception of crescendo transient ischaemic attacks (21% in urgent vs. 7% in early CEA; P = 0.001). The 30-day rates of stroke did not differ (P = 0.333) between patients with urgent (7.9%; 95% confidence interval 3.1%-17.7%) and early (4.4%; 95% confidence interval 2.4%-7.9%) CEA. The mortality and myocardial infarction rates were similar between the two groups. The median length of hospitalization was shorter in urgent CEA [6 days (interquartile range 4-6) vs. 10 days (interquartile range 7-14); P < 0.001]. CONCLUSIONS: Our findings highlight that urgent CEA performed within 2 days from the index event is related to a non-significant increase in the risk of peri-procedural stroke. The safety of urgent CEA requires further evaluation in larger datasets.

Safety of early endarterectomy in patients with symptomatic carotid artery stenosis: an international multicenter study.

BACKGROUND AND PURPOSE: Although the latest recommendations suggest that carotid endarterectomy (CEA) should be performed in symptomatic carotid artery stenosis (sCAS) patients within 2 weeks of the index event, only a minority of patients undergo surgery within the recommended time-frame. The aim of this international multicenter study was to prospectively evaluate the safety of early CEA in patients with sCAS in everyday clinical practice settings. METHODS: Consecutive patients with non-disabling acute ischaemic stroke (AIS) or transient ischaemic attack (TIA) due to sCAS (≥ 70%) underwent early (≤ 14 days) CEA at five tertiary-care stroke centers during a 2-year period. Primary outcome events included stroke, myocardial infarction (MI) or death occurring during the 30-day follow-up period and were defined according to the International Carotid Stenting Study criteria. RESULTS: A total of 165 patients with sCAS [mean age 69 ± 10 years; 69% men; 70% AIS; 6% crescendo TIA; 8% with contralateral internal carotid artery (ICA) occlusion] underwent early CEA (median elapsed time from symptom onset 8 days). Urgent CEA (≤ 2 days) was performed in 20 cases (12%). The primary outcomes of stroke and MI were 4.8% [95% confidence interval (CI) 1.5%-8.1%] and 0.6% (95% CI 0%-1.8%). The combined outcome event of non-fatal stroke, non-fatal MI or death was 5.5% (95% CI 2.0%-9.0%). Crescendo TIA, contralateral ICA occlusion and urgent CEA were not associated (P > 0.2) with a higher 30-day stroke rate. CONCLUSIONS: Our findings indicate that the risk of early CEA in consecutive unselected patients with non-disabling AIS or TIA due to sCAS is acceptable when the procedure is performed within 2 weeks (or even within 2 days) from symptom onset.

Brachial Artery-Brachial Vein Fistula for Hemodialysis: One- or Two-Stage Procedure-A Review.

Purpose The purpose of the study was to investigate the patency rate of the brachial vein transposition-arteriovenous fistula [BVT-AVF] and to review the available literature regarding the comparison of the one-stage with the two-stage procedure. Methods A multiple electronic health database search was performed, aiming to identify studies on brachial vein superficialization. Case reports and series with five or less patients were excluded from the study. End points of the study were the patency rates at 12, 24, and 36 months of follow-up. The patency of the one- or two-stage BVT-AVF procedure was investigated. Results Overall, 380 BVT-AVFs were analyzed. The primary patency rate at 12 months ranged between 24 and 77%. Rate of early fistula malfunction or failure of maturation of the fistula resulting in loss of functionality ranged from 0 to 53%. Forearm edema, hematomas, wound infection, and early thrombosis were among the most common complications. Limited data were available for the comparison of patency rates between the one- and the two-stage procedure because of the absence of sufficient comparative studies. However, series with one-stage procedure presented a lower patency rate at 12 months compared to series with two stages. Conclusion Patency rates after BVT-AVF, although not excellent, has encouraging results taking into account that patients undergoing these procedures do not have an accessible superficial vein network; failure of maturation and the increased rate of early postoperative complications remain a concern. The BVT-AVF is a valuable option for creating an autologous vascular access in patients lacking adequate superficial veins.

A HEALth Promotion and STRESS Management Program (HEAL-STRESS study) for prehypertensive and hypertensive patients: a quasi-experimental study in Greece.

Current hypertension guidelines advocate strategies encouraging healthy lifestyle behaviours. So far, there is a paucity of studies for the efficacy of such multifaceted programmes. The aim of this study is to investigate the efficacy of an 8-week health-promotion programme for lowering blood pressure (BP) in prehypertensive and hypertensive patients in the community. This was a quasi-experimental study using wait-list controls of 548 patients. The intervention group was administered with an 8-week health-promotion intervention. Measurements included home BP, smoking, body mass index (BMI), perceived stress, depression, anxiety and Health Locus of Control. After adjusting for confounders, the intervention group had a significant reduction in both systolic BP (SBP; mean -2.62 mm Hg, 95% confidence interval (CI): -1.29 to -3.96) and diastolic BP (DBP; mean -1.0, 95% CI: -0.93 to -1.9) compared with controls. In all, 14.9% of patients in the intervention group had >10 mm Hg reduction in SBP vs 4.4% in the control group (P<0.001, numbers needed to treat (NNT)=10). With regards to DBP, 21.7% of patients in the intervention group had >5 mm Hg reduction vs 12.5% in the control group (P=0.01, NNT=11). In terms of effect size, moderate-to-large improvements of BMI, perceived stress, anxiety, depression, external and chance Health Locus of Control were recorded. Changes in SBP and DBP were attributed to BMI and depressive symptom reductions, respectively. Comprehensive non-pharmaceutical programmes for BP management are strongly encouraged. Their long-term benefits on cardiovascular morbidity and mortality remain to be established by future research.

Venous wall function in the pathogenesis of varicose veins.

Three theories have been proposed to explain the cause of varicose veins, citing three different factors as the primary cause: valvular incompetence, a weakness of the vein wall, and increased arterial inflow associated with multiple arteriovenous communications. This study was designed to determine the cause of varicose veins with respect to these three factors. Duplex scanning techniques were used to assess the venous valves, and simultaneous measurements of calf volume (strain-gauge plethysmography) and venous pressure made during venous occlusion plethysmography were used to determine the elasticity of the venous wall and the rate of arterial inflow. Fifty-one control legs and 36 legs with superficial venous insufficiency were examined. Risk factors were used to divide the control legs into two groups: low risk or normal (23 legs) and high risk (28 legs). The results obtained in the high-risk limbs demonstrated a significantly reduced vein wall elasticity (p less than 0.001) and increased arterial inflow (p less than 0.005) compared with the normal limbs, with no corresponding increase in the incidence of valvular incompetence. These results clearly suggest that the role of the venous valves in the development of varicose veins is secondary to changes in the elastic properties of the vein wall and the rate of arterial inflow.

Evolving techniques in the treatment of carotid artery kinking: the use of resected redundant arterial segment.

Internal carotid artery kinking is frequently accompanied by atheromatous disease at the carotid bifurcation, and in this case both lesions may be treated simultaneously. Various surgical techniques have been used to correct carotid kinking but no particular one has been widely established. We conducted a retrospective review of 18 patients operated upon for internal carotid kinking during the last 5 years, which represents 4.1 per cent of the total carotid procedures performed during the same period. In 13 of the 18 patients carotid endarterectomy was performed before the repair of the kink. In four patients resection of the kinked segment with end-to-end anastomosis was performed combined with longitudinal arteriotomy at the carotid bifurcation. Two patients developed restenosis at the site of anastomosis requiring reoperation with patch angioplasty. Three patients were treated with eversion endarterectomy and end-to-side anastomosis, whereas in six patients we performed resection of the redundant internal carotid artery combined with longitudinal arteriotomy at the bifurcation. The posterior wall was reconstructed with interrupted sutures and the procedure was completed with patch angioplasty of the anterior wall. In four of these cases we used the autogenous resected arterial segment as patch material. None of these patients developed restenosis or symptoms in a follow-up period of 3 to 32 months. In cases in which significant carotid artery stenosis and internal carotid kinking coexist resection of the involved segment with end-to-end anastomosis of the posterior wall and patch angioplasty using the resected autogenous arterial segment constitute a convenient and satisfactory method of reconstruction.

Noninvasive tests in venous insufficiency.

Chronic venous insufficiency (CVI) is the result of outflow obstruction, reflux or a combination of both. Noninvasive tests detect an quantify obstruction and reflux if present and define the anatomic localisation of the abnormality. In evaluating CVI noninvasive tests combine physiologic and imaging techniques. These tests are widely available, simple, quick and cost-effective and therefore they are the methods of choice for initial objective evaluation. Different tests provide answers to different questions. The optimum clinically useful information can be now obtained using only three instruments: pocket Doppler, duplex or color duplex scanner and air plethysmography. The value of ambulatory venous pressure, photoplethysmography and light reflection reography, air plethysmography, duplex and color duplex scanning to assess reflux and the value of tests to assess out-flow obstruction are presented. Pooled data collected from large studies are also presented for reference. Qualitative and quantitative assessment of CVI are useful both for clinical assessment and to evaluate the effect of treatments.

Rupture of an abdominal aortic aneurysm following acute descending thoracic aortic dissection. Case report.

The coexistence of an abdominal aortic aneurysm and an acute aortic dissection seems to be rare and only a few reports are to be found in the literature. We report a case of a patient with acute aortic dissection of the descending thoracic aorta that caused rupture of a pre-existing abdominal aortic aneurysm. The literature is also thoroughly reviewed.

Simultaneous laser Doppler and transcutaneous oxygen tension measurements in claudicant patients.

Laser Doppler (LD) flux and transcutaneous oxygen tension (TcPO2) were measured in supine and sitting position at the dorsum of the foot with local skin temperature of 37 degrees C and 44 degrees C in 50 patients with stage IIb of chronic peripheral arterial occlusive disease (CPAOD) and in 30 healthy controls. The statistical analysis showed no significant differences between patients and controls in the supine and sitting position at 37 degrees C. A lower increase of LD- flux and TcPO2 could be noticed during hyperthermia and reactive hyperaemia in the patients group as well as a significant prolongation of oxygen (ORT) and flux reappearance time, of postocclusion time to peak flux and oxygen peak, of postocclusion time to half of peak flux and oxygen peak and of time to flux restoration at preocclusion levels (FTMAX) during reactive hyperaemia test. FTMAX and ORT allowed a clear separation between patients and controls and exhibited a high reproducibility. A regression analysis equation was derived with the most significant parameters indicating the presence and the severity of the disease. Moreover, the estimated time parameters of LD - flux and TcPO2 were correlated with the US - Doppler ankle systolic blood pressure indices and therefore with the impairment of the macrocirculation. In summary, we find that skin perfusion in patients with intermittent claudication is not different from normal subjects under basal conditions. However, maximal perfusion is reduced and the time to peak perfusion after a provocative stimulus is delayed.(ABSTRACT TRUNCATED AT 250 WORDS)

The effect of enalapril on leg muscle blood flow in patients with claudication.

In the percent study the authors have demonstrated that the peripheral blood flow and resistance as measured by strain-gauge venous occlusion plethysmography were favourably altered by enalapril. The peripheral blood flow increased significantly and since there was no detectable change in ankle pressure this indicated a decrease in resistance during administration of the drug.

Evaluation of skin blood flow and venoarteriolar response in patients with diabetes and peripheral vascular disease by laser Doppler flowmetry.

Skin blood flow in the distal foot was evaluated in patients with peripheral vascular disease and diabetes and compared with skin blood flow in normal volunteers by use of laser Doppler flowmetry. Resting blood flow (RBF) and standing blood flow (SBF) were recorded in a room at a constant temperature (20-22 degrees C). The RBF was found to be different in the five groups (normal, diabetics, patients with intermittent claudication, those with rest pain and those with impending gangrene. In diabetics RBF was significantly higher than in normal subjects. Even on standing, SBF in diabetics was higher and not different from RBF, indicating an ineffective venoarteriolar response (VAR). The VAR was also reduced in patients with claudication and was abolished in patients with rest pain and impending gangrene. In patients with rest pain SBF was increased. Laser Doppler flowmetry is a useful technique for evaluating skin perfusion in patients with peripheral arterial disease and for discriminating among different classes of patients.

Endovascular sclerotherapy, surgery, and surgery plus sclerotherapy in superficial venous incompetence: a randomized, 10-year follow-up trial--final results.

The study was planned to evaluate efficacy and costs of endovascular sclerotherapy (ES) in comparison with surgery and surgery associated with sclerotherapy in a prospective (10-year follow-up), good-clinical-practice study. Patients with varicose veins and pure, superficial venous incompetence were included. Of the patients randomized into the three groups 39 (group A) were treated with ES, 40 (B) with surgery + sclerotherapy, and 42 with surgery only (C). Surgery consisted of ligation of the SFJ (saphenofemoral junction) and of incompetent veins detected with color duplex. Of the preselected 150 patients, 121 subjects entered the study; 96 completed the 10-year follow-up (mean age 52.6 +/- 6 years; 51 men, 45 women). Dropouts were due to nonmedical problems. At 10 years no incompetence was observed in subjects treated with SPJ ligation (B and C). In the ES group 18.8% of the SFJs were patent and incompetent and in 43.8% of limbs the distal (below-knee) venous system was still incompetent [16.1% in the surgery + sclerotherapy group (p < 0.05) and 36% in the group treated with surgery only (p < 0.05 vs B and 0.05 vs A)]. Color duplex of the long saphenous vein indicated atrophy or obstruction of a segment (average 6.7 cm) after SFJ ligation (4.2 cm after ES). The cost of ES was 68% of surgery while the cost of surgery and sclerotherapy was 122% of surgery only. Endovascular sclerotherapy is an effective, cheaper treatment option, but surgery after 10 years is superior.

Comparison of low-molecular-weight heparin, administered primarily at home, with unfractionated heparin, administered in hospital, and subcutaneous heparin, administered at home for deep-vein thrombosis.

In this study, 294 patients with acute proximal DVT (deep venous thrombosis) were randomly assigned to receive intravenous standard heparin in the hospital (98 patients) or low-molecular-weight heparin (LMWH) (nadroparin 0.1 mL [equivalent to 100 AXa IU] per kg of body weight subcutaneously twice daily) administered primarily at home (outpatients) or alternatively in hospital (97 patients) or subcutaneous calcium heparin (SCHep) (99 patients, 0.5 mL bid) administered directly at home. The study design allowed outpatients taking LMWH heparin to go home immediately and hospitalized patients taking LMWH to be discharged early. Patients treated with standard heparin or LMWH received the oral anticoagulant starting on the second day, and heparin was discontinued when the therapeutic range (INR 2-3) had been reached. Anticoagulant treatment was maintained for 3 months. Patients treated with SCHep were injected twice daily for 3 months without oral anticoagulants. Patients were evaluated for inclusion and follow-up with color duplex scanning. Venography was not used. In case of suspected pulmonary embolism (PE) a ventilatory-perfusional lung scan was performed. Endpoints of the study were recurrent or extension of DVT, bleeding, the number of days spent in hospital, and costs of treatments. Of the 325 patients included, 294 completed the study. Dropouts totaled 31 (10.5%); six of the 325 included patients (1.8%) died from the related, neoplastic illness. Recurrence or extension of DVT was observed in 6.1% of patients in the LMWH group, in 6.2% in the standard heparin group, and in 7.1% in the SCHep group. Most recurrences (11/17) were in the first month in all groups. Bleedings were all minor, mostly during hospital stay. Hospital stay in patients treated with LMWH was 1.2+/-1.4 days in comparison with 5.4+/-1.2 in those treated with standard heparin. There was no hospital stay in the SCHep group. Average treatment costs in 3 months in the standard heparin group (US $2,760) were considered to be 100%; in comparison costs in the LMWH group was 28% of the standard heparin and 8% in the SCHep group. This study indicated that LMWH and SCHep can be used safely and effectively to treat patients with proximal DVT at home at a lower cost.

Treatment of severe intermittent claudication with pentoxifylline: a 40-week, controlled, randomized trial.

The efficacy, safety, and cost of pentoxifylline (PXF) in the treatment of severe intermittent claudication were studied comparing PXF and placebo in a randomized 40-week study. A treadmill test was performed at inclusion and at the end of weeks 20 and 40. A progressive training plan and the control of risk factors (with antiplatelet treatment) were used in both groups. Of the 200 included patients, 178 completed the study: 88 in the PXF group and 90 in the placebo group. There were 22 dropouts. The two groups were comparable for age, sex distribution, and for the presence of risk factors and smoking. There was a significant increase in pain-free walking distance (PFWD) in both groups. The absolute and percent increase in PFWD was significantly greater in the PXF group (p<0.05). At 20 weeks, the increase was 360.5% in the PXF vs 252% in the placebo group. At 40 weeks, the increase was 386% in the PXF and 369% in the placebo group (p<0.02). Total walking distance (TWD) increased at 20 weeks (up to 254%) and up to 329% at 40 weeks. In the placebo groups the increase was 158% at 20 weeks and 183% at 40 weeks. The excess increase produced by PXF treatment was 30% at 20 weeks and 38% at 40 weeks (p<0.02). Unwanted effects treatment was well tolerated. No serious drug-related side effects were observed. In summary, between-group analysis favors PXF considering walking distance and costs. Results indicate good efficacy and tolerability.

Treatment of long-distance intermittent claudication with pentoxifylline: a 12-month, randomized trial.

The efficacy, safety, and cost of pentoxifylline (PXF) in long-range (>400 m interval) intermittent claudication was studied comparing PXF and placebo in a 12-month study. A standardized treadmill test was performed at inclusion and at 6 and 12 months. A training plan based on walking was associated with the control of risk factor levels. Of the 194 included patients, 135 completed the study: 75 in the PXF group and 60 in the placebo group. There were 59 dropouts (due to low compliance). The authors observed a 148% increase in total walking distance (TWD) at 6 months with PXF (vs 110% with placebo; p<0.05); at 12 months, the increase was 170% with PXF (vs 131% with placebo; p<0.02). There was a 38% difference at 6 months and 39% at 12 months in favor of PXF. Treatment was well tolerated. In conclusion, PXF improved walking distance significantly better than placebo.

Treatment of intermittent claudication with pentoxifylline: a 12-month, randomized trial--walking distance and microcirculation.

The efficacy, safety and cost of pentoxifylline (PXF) in severe intermittent claudication was studied comparing PXF and placebo in a 12-month study. A treadmill test and microcirculatory evaluation with laser Doppler flowmetry were performed at inclusion and at the end of 6 and 12 months. A physical training plan (based on walking) and reduction in risk factor levels plan was used in both groups. Of the 120 included patients, 101 completed the study: 56 in the PXF group and 45 in the placebo group. There were 19 dropouts (due to low compliance). The two groups were comparable for age, sex distribution, walking distance, and the presence of risk factors and smoking. Intention-to-treat analysis indicated a 268% increase in walking distance in the PXF group (vs 198% in the placebo group; p<0.05) at 6 months and an increase of 404% (vs 280% in the placebo group; p<0.02) at 12 months. The absolute and percent increase in pain-free walking distance (PFWD) was greater in the PXF group (p<0.05). Treatment was well tolerated. No serious drug-related side effects were observed. Microcirculatory evaluation indicated an increase in flux (p < 0.05) in the PXF group (not significant in the placebo group); the after-exercise flux (AEF) was increased (p<0.05) in both groups at 6 months but the increase in AEF was greater in the PXF group at 12 month. In conclusion, between-group analysis favors PXF considering walking distance and microcirculatory parameters. Results indicate good efficacy and tolerability.

'Real' epidemiology of varicose veins and chronic venous diseases: the San Valentino Vascular Screening Project.

The aim of this study was to evaluate the prevalence and incidence of venous diseases and the role of concomitant/risk factors for varicose veins (VV) or chronic venous insufficiency (CVI). The study was based in San Valentino in Central Italy and was a real whole-population study. The study included 30,000 subjects in eight villages/towns evaluated with clinical assessment and duplex scanning. The global prevalence of VV was 7%; for CVI, the prevalence was 0.86% with 0.48% of ulcers. Incidence (new cases per year) was 0.22% for VV and 0.18% for CVI; 34% of patients with venous disease had never been seen or evaluated. The distribution of VV and CVI in comparison with duplex-detected incompetence (DI) indicates that 12% of subjects had only VV (no DI), 2% had DI but no VV, 7.5% had DI associated with VV, 2% apparent CVI without DI, 3% DI only (without CVI), and 1.6% both CVI and DI. VV associated with DI are rapidly progressive and CVI associated with DI often progresses to ulceration (22% in 6 years). VV without significant DI (3%) and venous dilatation without DI tend to remain at the same stage without progression for a lengthy time. New cases per year appear to have a greater increase in the working population (particularly CVI) possibly as a consequence of trauma during the working period. In older age (>80 years), the incidence of CVI tends to decrease. Ulcers increase in number with age. Only 22% of ulcers can be defined as venous (due to venous hypertension, increased ambulatory venous pressure, shorter refilling time, obstruction and DI). Medical advice for VV or CVI is requested in 164 subjects of 1,000 in the population. In 39 of 1,000, there is a problem but no medical advice is requested and in only 61 of 1,000, the venous problem is real. In VV in 78% of limbs, there is only reflux, in 8% only obstruction, and in 14% both. In CVI, 58% of limbs have reflux, 23% obstruction, and 19% both. In conclusion, VV and CVI are more common with increasing age. The increase with age is linear. There was no important difference between males and females. These results are the basis for future real, whole population studies to evaluate VV and CVI.

Nomograms used to define the short-term treatment with PGE(1) in patients with intermittent claudication and critical ischemia. The ORACL.E (Occlusion Revascularization in the Atherosclerotic Critical Limb) Study Group. The European Study.

Infusional, cyclic PGE1 treatment is effective in patients with intermittent claudication and critical limb ischemia (CLI). One of the problems related to chronic PGE1 treatment in vascular diseases due to atherosclerosis is to evaluate the variations of clinical conditions due to treatment in order to establish the number of cycles per year or per period (in severe vascular disease reevaluation of patients should be more frequent) needed to achieve clinical improvement. In a preliminary pilot study a group of 150 patients (mean age 67+/-12 years) with intermittent claudication (walking range from 0 to 500 m) and a group of 100 patients with CLI (45% with rest pain, and 55% gangrene; mean age 68 +/-11 years) the number of PGE1 cycles according to the short-term protocol (STP) needed to produce significant clinical improvement was preliminarily evaluated. Considering these preliminary observations, the investigators established a research plan useful to produce nomograms indicating the number of cycles of PGE1-STP per year needed to improve the clinical condition (both in intermittent claudication and CLI). A significant clinical improvement was arbitrarily defined as the increase of at least 35% in walking distance (on treadmill) and/or the disappearance of signs and symptoms of critical ischemia in 6 months of treatment in at least 75% of the treated patients. With consideration of the results obtained with the preliminary nomograms a larger validation of the nomograms is now advisable. A cost-effectiveness analysis is also useful to define the efficacy of treatment on the basis of its costs. The publication of this report in two angiological journals (Angeiologie and Angiology) will open the research on nomograms to all centers willing to collaborate to the study. The data are being collected in the ORACL.E database and will be analyzed within 12 months after the publication of this report.

PGE(1) treatment of severe intermittent claudication (short-term versus long-term, associated with exercise)--efficacy and costs in a 20-week, randomized trial.

The efficacy, safety, and cost of prostaglandin E1 (PGE1) in the treatment of severe intermittent claudication was studied comparing a long-term treatment protocol (LTP) with a short-term treatment protocol (STP) in a randomized 20-week study. The study included 980 patients (883 completed the study) with an average total walking distance of 85.5 +/-10 m (range 22-119). Phase 1 was a 2-week run-in phase (no treatment) for both protocols. In LTP, phase 2 was the main treatment phase. In the LTP, treatment was performed with 2-hour infusions (60 microg PGE1, 5 days each week for 4 weeks. In phase 3 (4-week interval period) PGE1 was administered twice a week (same dosage). In phase 4 (monitoring lasting 3 months, from week 9 to 20) no drugs were used. In STP phase 2 treatment was performed in 2 days by a 2-hour infusion (first day: morning 20 microg, afternoon 40 microg; second day morning and afternoon 60 microg). The reduced dosage was used only at the first cycle (week 0) to evaluate tolerability or side effects. Full dosage (60 microg bid) was used for all other cycles. The same cycle was repeated at the beginning of weeks 4, 8, and 12. The observation period was between weeks 12 and 20. A treadmill test was performed at inclusion, at the beginning of each phase, and at the end of 20th week. A similar progressive physical training plan (based on walking) and a reduction in risk factors levels plan was used in both groups. Intention-to-treat analysis indicated an increase in walking distance, which improved at 4 weeks and at 20 weeks in the STP more than in the LTP group. At 4 weeks the variation (increase) in pain-free walking (PFWD) was 167.8% (of the initial value) in the LTP group and 185% in the STP group (p<0.05). At 4 weeks the variation (increase) in total walking distance (TWD) was 227.6% of the initial value in the LTP group and 289% in the STP group (p<0.05). At 20 weeks the increase in PFWD was 496% of the initial value in the LTP group vs 643% in the STP group (147% difference; p<0.02). The increase in TWD was 368% in the LTP group and 529% in the STP group (161% difference; p<0.02). In both groups there was a significant increase in PFWD and TWD at 4 and 20 weeks, but results obtained with STP are better considering both walking distances. No serious drug-related side effects were observed. Local, mild adverse reactions were seen in 6.3% of the treated subjects in the LTP and 3% in the STP. Average cost of LTP was 6,664 Euro; for STP the average costs was approximately 1,820 E. The cost to achieve an improvement in walking distance of 1 m was 45.8 E with the LTP and 8.5 E with the STP (18% of the LTP cost; p<0.02). For an average 100% increase in walking distance the LTP cost was 1,989 E vs. 421 E with STP (p<0.02). Between-group analysis favors STP considering walking distance and costs. Results indicate good efficacy and tolerability of PGE, treatment. With STP less time is spent in infusion and more in the exercise program. STP reduces costs, speeds rehabilitation, and may be easily used in a larger number of nonspecialized units.