Results of the randomized, placebo-controlled clopidogrel and acetylsalicylic acid in bypass surgery for peripheral arterial disease (CASPAR) trial.

OBJECTIVE: Dual antiplatelet therapy with clopidogrel plus acetylsalicylic acid (ASA) is superior to ASA alone in patients with acute coronary syndromes and in those undergoing percutaneous coronary intervention. We sought to determine whether clopidogrel plus ASA conferred benefit on limb outcomes over ASA alone in patients undergoing below-knee bypass grafting. METHODS: Patients undergoing unilateral, below-knee bypass graft for atherosclerotic peripheral arterial disease (PAD) were enrolled 2 to 4 days after surgery and were randomly assigned to clopidogrel 75 mg/day plus ASA 75 to 100 mg/day or placebo plus ASA 75 to 100 mg/day for 6 to 24 months. The primary efficacy endpoint was a composite of index-graft occlusion or revascularization, above-ankle amputation of the affected limb, or death. The primary safety endpoint was severe bleeding (Global Utilization of Streptokinase and Tissue plasminogen activator for Occluded coronary arteries [GUSTO] classification). RESULTS: In the overall population, the primary endpoint occurred in 149 of 425 patients in the clopidogrel group vs 151 of 426 patients in the placebo (plus ASA) group (hazard ratio [HR], 0.98; 95% confidence interval [CI], 0.78-1.23). In a prespecified subgroup analysis, the primary endpoint was significantly reduced by clopidogrel in prosthetic graft patients (HR, 0.65; 95% CI, 0.45-0.95; P = .025) but not in venous graft patients (HR, 1.25; 95% CI, 0.94-1.67, not significant [NS]). A significant statistical interaction between treatment effect and graft type was observed (P(interaction) = .008). Although total bleeds were more frequent with clopidogrel, there was no significant difference between the rates of severe bleeding in the clopidogrel and placebo (plus ASA) groups (2.1% vs 1.2%). CONCLUSION: The combination of clopidogrel plus ASA did not improve limb or systemic outcomes in the overall population of PAD patients requiring below-knee bypass grafting. Subgroup analysis suggests that clopidogrel plus ASA confers benefit in patients receiving prosthetic grafts without significantly increasing major bleeding risk.

Thromboxane Antagonism with terutroban in Peripheral Arterial Disease: the TAIPAD study.

BACKGROUND: Terutroban is a selective prostaglandin endoperoxide (TP) receptor antagonist with antithrombotic, antivasoconstrictive and antiatherosclerotic properties and is currently in development for long-term cardiovascular secondary prevention. OBJECTIVES: TAIPAD is an international, double-blind, randomized controlled study comparing the effects of five dosages of oral terutroban vs. aspirin and placebo on platelet aggregation in peripheral arterial disease (PAD) patients. PATIENTS/METHODS: After 10 day's placebo run-in, included patients (n = 435; ankle-brachial pressure index, 0.7 ± 0.1) were randomly allocated to aspirin 75 mg day(-1), terutroban 1, 2.5, 5, 10 or 30 mg day(-1) or placebo. On day 5, the placebo group was reallocated to one of the terutroban groups for the rest of the study (day 83). Ex vivo platelet aggregation induced by the thromboxane analog U46619 (7 µm) was measured 24 h after dosing, as well as platelet aggregation induced by arachidonic acid (AA), collagen and ADP. RESULTS: Terutroban dose-dependently inhibited U46619-induced platelet aggregation at days 5 and 83. At day 5, the inhibition was significant vs. placebo for all terutroban dosages (P < 0.001). Terutroban (5, 10 and 30 mg day(-1)) was at least as effective as aspirin in inhibiting platelet aggregation induced by arachidonic acid (AA), collagen and adenosine diphosphate (ADP). Terutroban was well tolerated, with a safety profile similar to aspirin. CONCLUSIONS: In PAD patients, terutroban dose-dependently inhibited platelet aggregation 24 h after dosing, and was at least as effective as aspirin at 5, 10 and 30 mg day(-1). Terutroban was well tolerated.

Prevalence of peripheral artery disease and its associated risk factors in Spain: The ESTIME Study.

AIM: Several studies have demonstrated that patients with peripheral arterial disease (PAD), are at an increased risk of morbidity and mortality compared with those without PAD. However, few population-based studies have addressed the prevalence of PAD and intermittent claudication (IC). We assessed the prevalence of and the factors associated with PAD and IC in the Spanish population. METHODS: A cross sectional study with 1324 participants aged 55 to 84 years randomly selected from the census was conducted in 12 Spanish regions. The presence of PAD and IC was determined by an ankle-brachial index (ABI) <0.90 in either leg and by means of the Edinburgh questionnaire, respectively, fulfilled together with a detailed past history. All participants had blood pressure, body mass index, glycemia, and lipid profile measured. RESULTS: The response rate was 63.9% (846/1 324). ABI prevalence of PAD was 8.03% The prevalence of symptoms of definite or atypical IC was 6%. Subjects with an ABI <0.9 were more likely to be older, men, diabetics, current smokers, with coronary heart disease, with higher systolic pressure and with higher triglyceride levels than participants with ABI 0.9. CONCLUSIONS: ESTIME study confirms the high prevalence of asymptomatic PAD, and its relation with typical cardiovascular risk factors. ABI provides early diagnosis before claudication symptoms in a high proportion of patients. ABI could contribute to developing early prevention programmes.

A randomised open-label trial comparing long-term sub-cutaneous low-molecular-weight heparin compared with oral-anticoagulant therapy in the treatment of deep venous thrombosis.

OBJECTIVE: To evaluate whether low-molecular-weight heparin (LMWH) could be equally (or more) effective than oral anti-vitamin-K agents (AVK) in the long-term treatment of deep venous thrombosis (DVT). DESIGN: A randomised, open-label trial. MATERIAL AND METHODS: In this trial, 241 patients with symptomatic proximal DVT of the lower limbs confirmed by duplex ultrasound scan were included. After initial LMWH, patients received 6 months of treatment with full therapeutic dosage of tinzaparin or acenocoumarol. The primary outcome was the 12-month incidence of symptomatic recurrent venous thrombo-embolism (VTE). Duplex scans were performed at 6 and 12 months. RESULTS: During the 12-month period, six patients (5%) of 119 who received LMWH and 13 (10.7%) of 122 who received AVK had recurrent VTE (p=0.11). In patients with cancer, recurrent VTE tended to be lower in the LMWH group (two of 36 [5.5%]) vs. seven of 33 [21.2%]; p=0.06). One major bleeding occurred in the LMWH group and three in the AVK group. Venous re-canalisation increased significantly at 6 months (73.1% vs. 47.5%) and at 12 months (91.5% vs. 69.2%) in the LMWH group. CONCLUSIONS: Tinzaparin was more effective than AVK in achieving re-canalisation of leg thrombi. Long-term tinzaparin was at least as efficacious and safe as AVK for preventing recurrent VTE, especially in patients with cancer.

Vascular training and endovascular practice in Europe.

OBJECTIVE: To evaluate the influence of the status of vascular surgery (VS) training paradigms on the actual practice of endovascular therapy among the European countries. METHODS: An email-based survey concerning vascular surgery training models and endovascular practices of different clinical specialties was distributed to a VS educator within 14 European countries. European Vascular and Endovascular Monitor (EVEM) data also were processed to correlate endovascular practice with training models. RESULTS: Fourteen questionnaires were gathered. Vascular training in Europe appears in 3 models: 1. Mono-specialty (independence): 7 countries, 2. Subspecialty: 5 countries, 3. An existing specialty within general surgery: 2 countries. Independent compared to non-independent certification shortens overall training length (5.9 vs 7.9 years, p=0.006), while increasing overall training devoted specifically to VS (3.9 vs 2.7 years, p=0.008). Among countries with independent certification an average of 76% of aortic and 50% of peripheral endovascular procedures are performed by vascular surgeons, while the corresponding values, for countries with a non-independent certification, are 69% and 36% respectively. Countries with independent vascular certification, despite their lower average endovascular index (procedures per 100,000 population), reported a higher growth rate of aortic endovascular procedures (VS independent 132% vs VS non-independent 87%), within a four-year period (2003-2007). Peripheral endovascular procedures, though, have similar growth rates in both country groups (VS independent 62% vs VS non-independent 60%). CONCLUSIONS: In European countries with VS as an independent specialty, vascular surgeons have a shorter total training period but spend more time in VS training, although they may not undertake a greater proportion of the endovascular procedures their countries appear to have adopted endovascular technologies more rapidly compared to the ones with non-independent VS curricula. Whether such differences influence patient outcomes requires investigation in future studies.

Self-assessment of technical skill in surgery: the need for expert feedback.

INTRODUCTION: Technical skill has been formally assessed in the Fellow of the European Board of Vascular Surgery Examinations (FEBVS) since 2002. The aim of this study was to examine the relationship between expert assessment and trainee self-assessment. MATERIALS AND METHODS: Forty-two examination candidates performed a saphenofemoral junction (SFJ) ligation and an anterior tibial anastomosis on a synthetic simulation. Each candidate was rated by two examiners using a validated rating scale for their generic surgical skill for both procedures. Candidates then anonymously rated their own performance using the same scale. Parametric tests were used in the statistical analysis; a P-value < 0.05 was considered significant. RESULTS: The maximum mark in each assessment was 40; 24 was considered a competent score. The interobserver correlation for examiners marks were high (SFJ ligation, alpha = 0.68; distal anastomosis, alpha = 0.76). Examiners' marks were averaged. The mean examiner score for the SFJ ligation station was 27.8 (SD = 4.1) with 36 candidates (85.8%) attaining a competent score. The mean self-assessment score for this station was 30.7 (SD = 4.66). The mean examiners' marks for the distal anastomosis station was 29.2 (SD = 4.2); 39 candidates (92.8%) attained a competent score. The mean self-assessment score was 32.1 (SD = 4.0). There was no correlation between examiner and self-assessment scores in either station (Pearson's correlation coefficient: SFJ, r = 0.045, P = NS); distal anastomosis, r = 0.089, P = NS). Bland and Altman plots assessed the agreement between examiner and self-assessment. These showed candidates marked themselves higher than examiners with a mean difference of 2.9 marks in each station. CONCLUSIONS: Candidates' self-assessment and expert independent assessment correlate poorly. Trainees overestimate their ability according to independent assessment; regular technical feedback during training is, therefore, essential.

[Prevalence of peripheral artery disease evaluated by ankle brachial index in patients with metabolic syndrome. MERITO I study]. / Prevalencia de enfermedad arterial periférica estimada mediante el índice tobillo-brazo en pacientes con síndrome metabólico. Estudio MERITO I.

INTRODUCTION: Patients with Metabolic Syndrome have high cardiovascular morbidity and mortality rate above that expected when using accepted scales for risk stratification. Ankle brachial index (ABI) is an available, straightforward and reproducible method for the detection of peripheral vascular disease and for improving risk stratification in this population. Our study aimed to evaluate the prevalence of low ABI in patients with metabolic syndrome older than 50 years and to study the risk factors associated with its development. PATIENTS AND METHODS: 1519 subjects between 50 and 85 years, 935 of them with metabolic syndrome (Adult Treatment Panel III [ATP III] criteria), in primary prevention, without symptoms of intermittent claudication and who gave their consent to have an ABI measurement in internal medicine offices were included in the study. Cardiovascular risk factors were evaluated in all participants. An ABI < 0.9 was considered low. RESULTS: The prevalence of a low ABI in subjects with metabolic syndrome was 27.7 (95% CI: 24.8-30.5). Factors associated with low and a pathological ABI were age, higher serum creatinine levels and presence of proteinuria. After multivariate adjustment, only age (OR: 1.07; 95% CI: 1.04-1.09) and active tobacco use (OR: 1.45; 95% CI: 1.10-1.92) continued to be significant. CONCLUSION: Prevalence of a low ABI is elevated in subjects with metabolic syndrome without known cardiovascular disease and related with age and active tobacco use.

Impact of treatment on the quality of life in patients with critical limb ischaemia.

AIM: the purpose of this study was to assess the quality of life (QOL) in patients with critical lower limb ischaemia (CLI), and its modification after three types of therapeutical outcomes. MATERIALS AND METHODS: between January and December 2000 52 patients (36 male, mean age 68 years) treated for critical limb ischaemia (CLI) completed the Short Form (SF)-36 on admission and then 6 and 12 months later. Patients were divided in the 3 groups: Group I: revascularisation; Group II: major amputation; Group III: conservative treatment. Trends for each dimension over the follow-up and the effect of treatment group were assessed by an analysis of variance with repeated measurements. RESULTS: on admission, patients with CLI had a significantly worse health-related quality of life than a control population. Although some domains improved, some also deteriorated between baseline and 12 months and there was no significant difference between the three treatment groups. CONCLUSIONS: our results suggest that changes in dimensions of QOL obtained by limb revascularisation do not differ from those of other therapeutic approaches.

Factors increasing the mortality rate for patients with ruptured abdominal aortic aneurysms.

The objective of this report was to analyze the current surgical results of operative treatment in patients suffering ruptured AAA (abdominal aortic aneurysms) and to define those independent predictive factors for mortality. During a period of 2 years, from January 1996 to December 1997, 144 patients operated on for ruptured AAA in 10 hospitals were included in a multicenter retrospective study. Among the collected variables concerning each patient, those with potential relation to surgical mortality were studied: gender, age, diabetes, hypertension, cardiopathy, pulmonary obstructive disease, preoperative renal dysfunction, symptomatic cerebrovascular disease, peripheral vascular disease, hematocrit on admission, preoperative hypotension < 80 mmHg, loss of consciousness, cardiac arrest, aortic aneurysm location (infrarenal versus non-infrarenal), iliac involvement, aneurysm size, type of rupture, left renal vein ligature, ligature of a patent inferior mesenteric artery, place of aortic cross-clamping, type of grafting, exclusion of both hypogastric arteries, venous technical complications, associated surgery, use of cell saver, intraoperative blood loss, and postoperative complications (renal failure, sepsis, coagulopathy, cardiac complications, pulmonary complications, colon ischemia, prosthetic graft complications, and need for reoperation). Those variables with statistical significance in the univariate analysis were introduced into a multivariate logistic regression model to determine the independent predictors of death. From our results we concluded that surgery for ruptured abdominal aortic aneurysms continues to have an excessively high mortality rate. Even though some preoperative variables could be identified as predictors of mortality, an absolute mortality risk has not yet been determined and the decision to negate surgery should be individualized rather than taken on that basis only. Early diagnosis and treatment of symptomatic aneurysms would improve mortality figures and selective screening should be contemplated.

Primary aorto-oesophageal fistula due to oesophageal carcinoma. Report of a successfully managed case.

Aorto-oesophageal fistula is a rare but often fatal entity causing upper gastrointestinal bleeding. Amongst the different aetiologies described, the commonest is rupture of a thoracic aortic aneurysm into the oesophagus. This entity was first reported in 1818, and only recently have successfully treated cases been published. Other causes such as postoperative complications, tuberculosis and trauma are less common. Oesophageal malignancy perforating the aorta is a rarity. The authors describe a case of aortic perforation secondary to an oesophageal carcinoma, treated with initial success. The clinical onset was a massive upper gastrointestinal haemorrhage. The diagnosis, once the bleeding was controlled, was arrived at after CT-scanning and arteriography. A Dacron prosthesis was interposed into the descending thoracic aorta to restore aortic flow; later an oesophagectomy plus oesophagostomy and jejunostomy were carried out.

Captopril test and renal duplex scanning for the primary screening of renovascular disease.

To evaluate the utility of renal duplex scanning and the captopril test in the detection and functional assessment of renovascular disease, by comparing their results with those of angiography and captopril isotopic renography (CIR). Sixty hypertensive patients with aortoiliac disease and 16 with clinically suspected renovascular hypertension (RVH) were included. All the patients underwent renal duplex scanning prior to angiography. In addition, isotopic renograms and a determination of peripheral plasma renin activity (PRA) at baseline and 60 min after oral intake of 50 mg of captopril were both performed. A postcaptopril PRA > 5.7 ng/mL/h was considered as diagnostic of a positive captopril test. On the basis of the results of the angiography and isotopic renograms, all the patients were classified into three groups: group I (n = 33), essential hypertension (EHT); group II (n = 20), hypertension and angiographic RAS > 60% but negative CIR; and group III (n = 24), RAS > 60% and positive CIR. This last condition was considered as highly suspicious for RVH. Renal duplex scanning showed greater accuracy than captopril PRA or CIR for detecting RAS > 60% (groups II and III) with 87.3% versus 52.4% and 45.3% sensitivity (S), and 91.5% versus 84.4% and 92.8% specificity (Sp), respectively. The captopril test correctly identified 44 of 51 EHT patients (groups I and II) and 20 of 23 highly suspected of RVH (group III) with 87% S, 86.5% Sp, 74.1% PPV, and 93.6% NPV. Accuracy was further increased when a combined approach (renal duplex scanning and captopril test) was followed (82.6% S, 93.7% Sp, 86.4 PPV, and 91.8 NPV). In our study, renal duplex scanning was a useful screening method for detecting anatomical RAS. A combination of both renal duplex scanning and captopril test may be an appropriate approach to the primary screening for RVH, thereby permitting the selection of those patients indicated for angiography.

Value of Doppler parameters in the diagnosis of renal artery stenosis.

PURPOSE: Our purpose was to assess the accuracy and optimal threshold values of the Doppler parameters of the renal arteries and parenchyma for detecting renal artery stenosis (RAS) greater than 60% and occlusion. METHODS: Renal duplex ultrasonography and standard angiographic studies of the renal arteries were performed in 78 patients for comparative analysis. Three degrees of RAS were considered: less than 60%, greater than 60%, and occlusion. The following parameters of the Doppler wave were measured in the signal obtained from the main renal artery and interlobar arteries: peak systolic velocity (PSV), end-diastolic velocity, peripheral resistance index, acceleration time, acceleration index, and renal/aortic ratio (RAR). RESULTS: Logistic regression analysis identified the PSV in the renal artery as the best parameter to differentiate RAS less than 60% from RAS greater than 60%. Only when this parameter was excluded were the RAR and end-diastolic velocity in the renal artery the variables accepted as the best predictors. Receiver-operator curve analysis revealed a PSV in the main renal artery greater than 198 cm/sec and RAR greater than 3.3 as the best cutoff points for detecting RAS greater than 60%. A PSV above this threshold provided 87.3% sensitivity and 91.5% specificity. The RAR showed similar specificity (92.4% but a much lower sensitivity (76.4%). A kidney length less than 8.5 cm, in addition to an absent Doppler signal in renal parenchyma, was the best criterion to identify renal artery occlusion. On the basis of the above-mentioned criteria, renal duplex scanning correctly identified 86 of 94 cases of RAS less than 60%, 41 of 48 cases of RAS greater than 60%, and six of seven occlusions (kappa value = 0.8). CONCLUSION: These results suggest that the PSV in the renal artery is the best predicting Doppler parameter to detect RAS greater than 60%. A PSV greater than 198 cm/sec may be an appropriate cutoff point to diagnose this group of stenosis. The RAR did not add any predicting utility in this series. An absent Doppler signal in the renal parenchyma and a kidney length less than 8.5 cm were the best predictors of renal artery occlusion.

The role of the circle of Willis in carotid occlusion: assessment with phase contrast MR angiography and transcranial duplex.

PURPOSE: To study the collateral pathways recruited after occlusion of the internal carotid artery (ICA), and to evaluate its influence on the impairment of hemispheric blood flow supply and development of low flow infarcts. METHODS: 38 patients with ICA occlusion (18 asymptomatic; five transient ischaemic attacks; and 15 strokes) were included. Infarcts on cerebral MR scanning were categorised in order to differentiate patients with territorial infarcts or no lesion (group I; n = 22) from those with brain damage due to low flow (group II; n = 16). Patency and direction of flow in the communicating arteries were assessed by means of cine phase contrast MR angiography (PC-MRA). Flow velocity in the middle cerebral artery (MCA) was measured by means of transcranial Duplex (TCD). RESULTS: Cine PC-MRA revealed a reversed ophthalmic artery blood flow ipsilateral to the ICA occlusion in all except two patients in group I and one patient in group II (NS). Posterior to anterior flow in the ipsilateral posterior communicating artery (PCoA) was detected in 16 (73%) patients in group I and in 13 (81%) in group II (NS). In contrast, reversed blood flow in the ipsilateral A1 segment of the anterior cerebral artery, through a patent anterior communicating artery (ACoA), was identified in 19 (86%) patients of group I, vs. 7 (44%) of group II (p = 0.005). The relative risk of low-flow infarcts was significantly higher in those cases with non-functioning ACoA (odds ratio = 8.1; p < 0.05). TCD showed a lower peak systolic velocity (PSV) in the ipsilateral MCA than in the contralateral one (60 +/- 9 cm/s vs. 90 +/- 11 cm/s; p < 0.005). Those patients without crossed flow through the ACoA, showed an even lower PSV in the ipsilateral MCA (55 +/- 7 cm/s vs. 64 +/- 9 cm/s; p = 0.03). CONCLUSIONS: These data suggest that even though ICA occlusion may occur without cerebral damage, collateral blood supply is not enough to maintain normal hemispheric perfusion. The ACoA may be a key collateral pathway as a non-functioning ACoA is associated with an increased risk of developing low-flow infarcts.