Cost-effectiveness of revascularization in patients with intermittent claudication.

BACKGROUND: Revascularization is a treatment option for patients with intermittent claudication. However, there is a lack of evidence to support its long-term benefits and cost-effectiveness. The aim of this study was to compare the cost-effectiveness of revascularization and best medical therapy (BMT) with that of BMT alone. METHODS: Data were used from the IRONIC (Invasive Revascularization Or Not in Intermittent Claudication) RCT where consecutive patients with mild-to-severe intermittent claudication owing to aortoiliac or femoropopliteal disease were allocated to either BMT alone (including a structured, non-supervised exercise programme) or to revascularization together with BMT. Inpatient and outpatient costs were obtained prospectively over 24 months of follow-up. Mean improvement in quality-adjusted life-years (QALYs) was calculated based on responses to the EuroQol Five Dimensions EQ-5D-3 L™ questionnaire. Cost-effectiveness was assessed as the cost per QALY gained. RESULTS: A total of 158 patients were randomized, 79 to each group. The mean cost per patient in the BMT group was €1901, whereas it was €8280 in the group treated with revascularization in addition to BMT, with a cost difference of €6379 (95 per cent c.i. €4229 to 8728) per patient. Revascularization in addition to BMT resulted in a mean gain in QALYs of 0·16 (95 per cent c.i. 0·06 to 0·24) per patient, giving an incremental cost-effectiveness ratio of €42 881 per QALY. CONCLUSION: The costs associated with revascularization together with BMT in patients with intermittent claudication were about four times higher than those of BMT alone. The incremental cost-effectiveness ratio of revascularization was within the accepted threshold for public willingness to pay according to the Swedish National Guidelines, but exceeded that of the UK National Institute for Health and Care Excellence guidelines.

Two-year results from a randomized clinical trial of revascularization in patients with intermittent claudication.

BACKGROUND: Intermittent claudication is associated with significant impairment of health-related quality of life. The use of revascularization techniques to improve health-related quality of life remains controversial. METHODS: Patients with intermittent claudication due to iliac or femoropopliteal peripheral artery disease were enrolled in the IRONIC trial. They were randomized to either best medical therapy (BMT), including a structured, non-supervised exercise programme, or revascularization with either endovascular or open techniques in addition to BMT. The primary outcome was health-related quality of life at 2 years assessed using the Short Form 36 (SF-36(®) ) questionnaire. Secondary outcomes included VascuQoL questionnaire results, treadmill walking distances and achievement of patient-specified treatment goals. RESULTS: Both randomized groups had improved health-related quality of life and treadmill walking distance at 2-year follow-up. Overall SF-36(®) physical component summary score, three SF-36(®) physical domain scores, overall VascuQoL score, and three of five VascuQoL domain scores showed significantly greater improvement in the group that also received invasive treatment. Intermittent claudication distance on a graded treadmill improved more in the revascularization + BMT group (117 versus 55 m; P = 0·003) whereas maximum walking distance and 6-min walk test distance were similar. Some 44 per cent of patients in the revascularization + BMT group reported they had fully achieved their treatment goal versus 10 per cent in the BMT group. CONCLUSION: A revascularization strategy with unsupervised exercise improved health-related quality of life and intermittent claudication distance more than standard BMT and an unsupervised exercise programme in patients with lifestyle-limiting claudication. REGISTRATION NUMBER: NCT01219842 (http://www.clinicaltrials.gov).

Walking performance and health-related quality of life after surgical or endovascular invasive versus non-invasive treatment for intermittent claudication--a prospective randomised trial.

OBJECTIVES: Despite limited scientific evidence for the effectiveness of invasive treatment for intermittent claudication (IC), revascularisation procedures for IC are increasingly often performed in Sweden. This randomised controlled trial compares the outcome after 2 years of primary invasive (INV) versus primary non-invasive (NON) treatment strategies in unselected IC patients. MATERIALS/METHODS: Based on arterial duplex and clinical examination, IC patients were randomised to INV (endovascular and/or surgical, n = 100) or NON (n = 101). NON patients could request invasive treatment if they deteriorated during follow-up. Primary outcome was maximal walking performance (MWP) on graded treadmill test at 2 years and secondary outcomes included health-related quality of life (HRQL), assessed with Short Form (36) Health Survey (SF-36). RESULTS: MWP was not significantly (p = 0.104) improved in the INV versus the NON group. Two SF-36 physical subscales, Bodily Pain (p < 0.01) and Role Physical (p < 0.05) improved significantly more in the INV versus the NON group. There were 7% crossovers against the study protocol in the INV group. CONCLUSIONS: Although invasive treatment did not show any significant advantage regarding MWP, the HRQL improvements associated with invasive treatment tentatively suggest secondary benefits of this regimen. On the other hand, a primary non-invasive treatment strategy seems to be accepted by most IC patients.

Effects of three months of low molecular weight heparin (dalteparin) treatment after bypass surgery for lower limb ischemia--a randomised placebo-controlled double blind multicentre trial.

OBJECTIVES: To test the hypothesis that long-term postoperative dalteparin (Fragmin), Pharmacia Corp) treatment improves primary patency of peripheral arterial bypass grafts (PABG) in lower limb ischemia patients on acetylsalicylic acid (ASA) treatment. DESIGN: Prospective randomised double blind multicenter study. MATERIALS AND METHODS: Using a computer algorithm 284 patients with lower limb ischemia, most with pre-operative ischemic ulceration or partial gangrene, from 12 hospitals were randomised, after PABG, to 5000 IU dalteparin or placebo injections once daily for 3 months. All patients received 75 mg of ASA daily for 12 months. Graft patency was assessed at 1, 3 and 12 months. RESULTS: At 1 year, 42 patients had died or were lost to follow-up. Compliance with the injection schedule was 80%. Primary patency rate, in the dalteparin versus the control group, respectively, was 83 versus 80% (n.s.) at 3 months and 59% for both groups at 12 months. Major complication rates and cardiovascular morbidity were not different between the two groups. CONCLUSIONS: In patients on ASA treatment, long-term postoperative dalteparin treatment did not improve patency after peripheral artery bypass grafting. Therefore, low molecular weight heparin treatment cannot be recommended for routine use after bypass surgery for critical lower limb ischemia.

Predictors of treatment outcome in intermittent claudication.

OBJECTIVE: To derive formulae to predict the likely 12-month health-related quality of life outcome following different treatments for intermittent claudication (IC). DESIGN: A prospective, randomized, controlled study. MATERIALS: One hundred and seventy-one unselected patients with stable IC were sequentially randomized to invasive therapy, supervised physical training or observation. Hierarchical analysis was used to identify significant predictors of outcome. RESULTS: The strongest outcome predictors were baseline values of the respective outcome variables in all groups. No more than two significant secondary predictors were identified for each outcome variable and no outcome variable was a predictor of any other outcome variable. Resulting prediction equations achieved between 61 and 90% concordance with improvement (75% considered adequate), with best prediction for invasive therapy and poorest for observation. Suggested cutpoints for the various endpoints in the three groups had sensitivities ranging between 65 and 100% and false positive rates between 5 and 50%. CONCLUSIONS: The derived equations adequately predicted improvement on the various outcome variables in invasive therapy and supervised physical training, and may serve as aids in selecting patients likely to benefit most from a particular treatment strategy. The uniqueness of the outcome variables underscores the importance of implementing a comprehensive set of endpoints relevant to the impacts of the condition.

Treatment efficacy of intermittent claudication by surgical intervention, supervised physical exercise training compared to no treatment in unselected randomised patients I: one year results of functional and physiological improvements.

OBJECTIVES: to compare the effect of surgery, exercise and simple observation on maximum exercise power in claudicants. DESIGN: prospective, randomised study. METHODS: a total of 264 unselected claudicants were randomised to supervised exercise training, invasive treatment (open surgical or endovascular procedures) or observation. One year treatment outcomes were analysed on an intention to-treat basis. RESULTS: invasively treated patients showed a significant improvement in maximum walking power, stopping distance, post-ischaemic blood flow and big toe pressure at one year. Patients randomised to physical exercise training or to the control group did not improve in any outcome measure. CONCLUSION: invasive treatment increased walking capacity, leg blood pressure and flow. Supervised physical exercise training offered no therapeutic advantage compared to untreated controls.

Treatment efficacy of intermittent claudication by invasive therapy, supervised physical exercise training compared to no treatment in unselected randomised patients II: one-year results of health-related quality of life.

OBJECTIVE: to compare the effectiveness of invasive therapy, supervised physical training and no treatment in terms of health-related quality of life (HRQL) in patients with intermittent claudication (IC). DESIGN: a prospective, randomised, controlled study. MATERIALS: a total of 253 unselected patients with stable IC were sequentially randomised into 3 balanced treatment groups. At 1 year follow-up data from a battery of generic and disease specific HRQL questionnaires, and global indices of quality of life and physical condition were available in 171 patients. RESULTS: compared with a non-diseased reference group, claudicants were substantially limited in daily physical functioning, but little affected regarding emotional, cognitive and social functioning, or well-being. Invasive therapy yielded significantly greater improvements in some aspects of physical functioning and walk-related symptoms than training. Training was not superior to invasive therapy on any HRQL dimension and superior to no treatment on only one dimension. Treatment effects, however, were generally small-to-moderate and levels of physical dysfunction in all groups remained higher than reference values. CONCLUSIONS: invasive therapy is more effective than supervised training in alleviating illness-specific symptoms and improving certain aspects of physical functioning - the primary HRQL domains impacted on by IC and the principal goals of its treatment. However, since treatment effect sizes were at most moderate and given that untreated claudicants reported at most small deterioration in HRQL, the level of evidence supporting invasive therapy is modest.

[Ruptured abdominal aortic aneurysm. Endovascular treatment under local anesthesia]. / Rupturerat bukaortaaneurysm. Endovaskulär behandling i lokalanestesi.

We report on endovascular repair of a ruptured abdominal aortic aneurysm. A bifurcated stent graft was inserted under local anesthesia. Aortic clamping is rapidly provided by percutaneous placement of an aortic occlusion balloon catheter. Carbon dioxide can usually replace conventional contrast in patients with renal insufficiency. This minimally invasive procedure may reduce perioperative morbidity and mortality in patients with ruptured aortic aneurysms. The advantages and limitations of this novel technique are discussed.

Hypertonic saline infusion with or without dextran 70 in the reperfusion phase of experimental acute limb ischaemia.

OBJECTIVES: To study the efficacy of hypertonic fluid therapy on central haemodynamics, leg blood flow, and skeletal muscle metabolism at reperfusion after subtotal bilateral limb ischaemia. DESIGN: Prospective, randomised, controlled study, in pigs (n = 24). METHODS: Bilateral limb ischaemia was induced (aortic balloon catheter) and central haemodynamics, peripheral blood flow-thoracic fluid content, blood chemistry, and skeletal muscle metabolite levels were monitored. After 235 min of ischaemia infusion of normal 0.9% saline (NS), hypertonic 7.5% saline (HS), or HS in 6% dextran 70 (HSD) was started. Five minutes later the aortic balloon was deflated and the haemodynamic and metabolic alterations were studied for 180 min after reflow. RESULTS: Aortic occlusion resulted in haemodynamic alterations, reduced limb perfusion and metabolic changes indicative of tissue ischaemia. The haemodynamic support prior to, and following, deflation of the aortic balloon was more efficient for HS and HSD than for NS. Lactate clearance and restitution of high energy phosphagen levels in skeletal muscle were faster and more pronounced in the HS and HSD groups. CONCLUSIONS: Small-volume hypertonic saline, especially in combination with 6% dextran 70, will effectively reverse limb ischaemia induced haemodynamic and tissue metabolic disturbances.

VIP-antiserum and indomethacin inhibit calcium and bicarbonate secretion by the inflamed feline gallbladder mucosa.

Ionized calcium (Ca2+) and bicarbonate (HCO(3)-) are important ions for gallstone formation. In the present study the effect of indomethacin and vasoactive intestinal peptide-antiserum (VIP-antiserum) on the Ca2+, HCO(3)- and fluid secretion in the inflamed gallbladder were tested in a validated experimental model in cats. The animals were studied in acute experiments 6 weeks after cystic duct ligation and gallstone implantation. During basal conditions there was a continuous secretion of Ca2+, HCO(3)- and fluid into the lumen of the inflamed gallbladder. Indomethacin and VIP-antiserum inhibited the Ca2+, HCO(3)- and fluid secretion across the inflamed gallbladder mucosa. Intraluminal amiloride inhibited the absorption of Ca2+, HCO(3)- and fluid after indomethacin infusion. An impaired absorption of Ca2+, HCO(3)- and fluid in the inflamed gallbladder is probably important for the solubility of calcium salts in the early stages of inflammation in the gallbladder mucosa.

Oral ciprofloxacin versus intravenous cefuroxime as prophylaxis against postoperative infection in vascular surgery: a randomised double-blind, prospective multicentre study.

OBJECTIVES: To test the hypothesis that oral ciprofloxacin is equally effective as intravenous cefuroxime in preventing postoperative infectious complications in patients undergoing peripheral arterial surgery involving the groins. DESIGN: Prospective, randomised, double-blind multicentre study. MATERIALS: 580 patients undergoing arterial surgery involving the groins were randomised to ciprofloxacin (Ciproxin, Bayer) 750 mg x 2 p.o. or cefuroxime (Zinacef, Glaxo) 1.5 g x 3 i.v. given only on the day of surgery. The primary endpoint was wound/graft infection within 30 days postoperatively. Wound infection was defined as pus. RESULTS: The wound infection rate in the ciprofloxacin group was 9.2% (27 patients) and in the cefuroxime group 9.1% (26 patients) according to intention to treat. For correct treatment the corresponding numbers were 9.5% (23 patients) and 9.7% (22 patients), respectively. There were three graft infections (0.5%). The infection rate was 7.1% (31/433) in the absence and 14.9% (22/147) in the presence of distal ulcers (p < 0.05). S. allreus was the most common bacteria isolated. Forty percent of the wound infections were localised to the groins. By multivariate analysis presence of distal ulcer was the only factor of prognostic significance. CONCLUSIONS: The infection rate was similar in the two groups. Thus, oral administration of ciprofloxacin is an attractive, cost-effective and safe alternative to prophylaxis in vascular patients capable of taking oral medication on the day of surgery.

Inflammation reduces mucosal secretion of hydrogen ions and impairs concentrating function and luminal acidification in feline gallbladder.

BACKGROUND: The gallbladder mucosa normally absorbs fluid and secretes H+ ions. The fluid secretion in inflamed gallbladders is induced by prostaglandins and mediated by intramural vasoactive intestinal peptide (VIP)-ergic nerves. METHODS: The influence of inflammation on gallblader contents due to secretion of H+ into the lumen. In animals with inflamed gallbladder this acid secretion was reduced; there was secretion of HCO3- and no evident acidification of the gallbladder contents. Injection of VIP antiserum or indomethacin restored H+ secretion and inhibited HCO3- and fluid secretion by the inflamed gallbladder mucosa. An impaired acidification of the gallbladder contents due to mucosal inflammation may reduce the solubility of calcium salts in gallbladder bile and increase the risk of their precipitation in the lumen. CONCLUSION: Mucosal inflammation reduces H+ secretion and impairs acidification of the gallbladder contents.

Effects of spinal cord stimulation (SCS) in patients with inoperable severe lower limb ischaemia: a prospective randomised controlled study.

OBJECTIVES: This study was designed to test the hypothesis that spinal cord stimulation (SCS) improves limb salvage in patients with inoperable severe leg ischaemia. DESIGN: Prospective randomised controlled study with 18 months follow-up. SETTING: Vascular surgical units in two university hospitals. MATERIALS: Atherosclerotic (n = 41) and diabetic (n = 10) patients having chronic leg ischaemia with rest pain and/or ischaemic ulcerations due to technically inoperable arterial occlusions. CHIEF OUTCOME MEASURES: Limb salvage and amount of tissue loss within 18 months, pain relief. MAIN RESULTS: Twenty-five patients were randomized to SCS and 26 to analgesic (control) treatment. Macrocirculatory parameters were not different in the two groups during follow-up. Long-term pain relief was observed only in the SCS group. At 18 months, limb salvage rates in the SCS and control groups were 62% and 45% (N.S.). Tissue loss was less (p = 0.05) in the SCS group. A subgroup analysis of patients without arterial hypertension showed a significantly lower amputation rate in the SCS vs the control group. CONCLUSIONS: SCS provided long-term pain relief but limb salvage at 18 months was not significantly improved by SCS in this rather small study. The results suggest that SCS may reduce amputation levels in patients with severe inoperable leg ischaemia and be most effective in patients without arterial hypertension.