The long-term recurrence risk of patients with unprovoked venous thromboembolism: an observational cohort study.

Essentials Long-term recurrence risk of venous thromboembolism (VTE) is uncertain. We performed a prospective cohort study of 839 patients with first unprovoked VTE. VTE recurrence risk is high, particularly in men with proximal thrombosis or pulmonary embolism. Sex and VTE site determine the recurrence risk and should be considered for patient counseling. SUMMARY: Background The long-term recurrence risk (ltRR) of venous thromboembolism (VTE) is uncertain. Objective To assess the ltRR of patients with first unprovoked VTE. Patients/methods Patients were classified into three categories: distal deep vein thrombosis (DVT), proximal DVT or pulmonary embolism (PE), that is, PE associated with DVT or isolated PE. Patients with major thrombophilia or antithrombotic therapy were excluded. The endpoint was recurrent symptomatic VTE. Results A total of 839 patients were followed for a median of 7.7 years. VTE recurred in 263 patients (31%). After 10 and 20 years, the cumulative ltRR was 32% (95% confidence interval [CI], 29-36) and 44% (95% CI, 38-49) with 3.9 (95% CI, 3.3-4.6) and 3.3 (95% CI, 2.7-4.0) events per 100 patient-years, respectively. The adjusted hazard ratio was 2.1 (95% CI, 1.4-3.2) and 2.1 (95% CI, 1.4-3.2) for patients with proximal DVT or PE compared with patients with distal DVT and was 2.1 (95% CI, 1.6-2.9) for men compared with women. At 10 years, 4.7 (95% CI, 3.8-5.8) events per 100 patient-years occurred in men with proximal DVT or PE, 2.4 (95% CI, 1.2-4.4) in men with distal DVT, 1.9 (95% CI, 1.2-2.8) in women with proximal DVT or PE and 0.9 (95% CI, 0.2-1.9) in women with distal DVT. Conclusion The ltRR of patients with first unprovoked VTE is high and dependent upon sex and VTE site.

Consensus Document on Intermittent Claudication from the Central European Vascular Forum (C.E.V.F.)-3rd revision (2013) with the sharing of the Mediterranean League of Angiology and Vascular Surgery, and the North Africa and Middle East Chapter of International Union of Angiology.

This paper is the review of the Consensus Document on Intermittent Claudication of the Central European Vascular Forum (CEVF), published in 2008, and and shared with the North Africa and Middle East Chapter of International Union of Angiology and the Mediterranean League of Angiology and Vascular Surgery. The Document presents suggestions for general practitioners and vascular specialists for more precise and appropriate management of PAD, particularly of intermittent claudication, and underlines the investigations that should be required by GPs and what the GP should expect from the vascular specialist (angiologist, vascular surgeon). The idea of the Faculty is to produce a short document, which is an easy reference in daily clinical practice, both for the GPs and vascular specialists.

Femoral stenting: what do the guidelines tell us.

Recommendations in guidelines should reflect current knowledge due to results of well-designed randomized clinical trials. However, one of the main problems with guidelines concerning revascularization in patients with peripheral arterial disease (PAD) is the lack of such clinical trials with a paucity of so called level I data. Furthermore, vascular interventions are practiced by physicians with different medical, surgical and radiologic speciality training background. An inter-society consensus statement by its very nature coalesces into one document the divergent experiences, interests and also interpretation of the literature by the participating parties, in our case mainly vascular surgeons and non-surgical interventionists. Therefore the recommendations in such international multi-societal consensus documents--such as the TASC document--are a compromise due to the necessity to be accepted by the different societies. Therefore often it remains difficult to follow such recommendations in clinical routine. A major problem of all guidelines is the problem of contemporaneity so that recent developments often cannot be included or discussed. Furthermore, in international guidelines no acknowledgement can be made of country- and/or center-specific differences.

Innovative technologies for SFA occlusions: drug coated balloons in SFA lesions.

The concept of using a balloon catheter to directly deliver an antiproliferative drug at the site of injury has become one of the most interesting technological developments in endovascular therapy. There have been important advances in knowledge concerning balloon-based drug delivery technologies during the last years, and different methods have been developed by different companies to coat the balloon with the antiproliferative agent. Currently there is a rapidly increasing clinical study program using drug coated balloons (DCB) in different locations and indications. There are four already finished randomized studies in patients with superficial femoral artery lesions investigating the efficacy of paclitaxel release by DCB, and all demonstrated significantly improved patency rates compared to balloon angioplasty with non coated balloons. DCB offer several advantages compared to drug eluting stents, since any stentless technology for improvement of longterm patency is preferable to overcome the drawbacks of stenting. This technology has demonstrated the capacity to have a significant impact on the practice of percutaneous cardiovascular interventions in the future.

Drug-eluting stents above the knee.

There are only very few trials concerning use of drug-eluting stents (DES) in the femoropopliteal segment. While earlier trials using a sirolimus-eluting polymer-coated stent and an everolimus-eluting stent failed to demonstrate improved mid-term patency compared with a bare-metal stent, the recently presented ­ however still unpublished - data with the Zilver PTX stent using a polymer-free paclitaxel coating are very promising. Before we can make definite conclusions and recommendations, we have to see longer-term follow-up data. A potential future improvement of local drug application for the necessary time span without the disadvantages of permanent stent implantation can be expected by the development of completely bioabsorbable DES.

Evidence of carotid atherosclerosis in orthopantomograms and the risk for future cardiovascular events.

BACKGROUND: Evidence of carotid atherosclerosis can be detected in 3 to 5% of orthopantomogram (OPG) investigations. The clinical impact of these findings is unknown. We investigated the association of OPG findings of carotid atherosclerosis with the occurrence of future cardiovascular adverse events. PATIENTS AND METHODS: We randomly selected 411 of 1268 participants with pre-existent cardiovascular disease from the prospective Inflammation in Carotid Arteries Risk for Arthrosclerosis Study (ICARAS) and assessed their OPGs for the presence of calcified atherosclerotic lesions or indirect signs of atherosclerosis, such as surgical clips or intravascular stents. The degree of carotid stenosis was measured by duplex ultrasound investigations. Patients were then followed for median 39 months (interquartile range 33 to 44 months) for the occurrence of major adverse cardiovascular events (MACE) including myocardial infarction, coronary revascularisation, stroke and death. RESULTS: We found no statistically significant association between the presence of carotid atherosclerosis detected on OPGs and the presence of a significant carotid stenosis (left carotid artery kappa=0.08; right carotid artery kappa=0.12), or the degree of carotid stenosis (P=0.20). Furthermore, the presence of OPG signs of carotid atherosclerosis was not statistically significant associated with future MACE (adjusted hazard ratio 0.92, 95% confidence interval 0.59 to 1.42; P=0.70). CONCLUSIONS: Evidence of carotid plaque revealed by OPGs in patients with previously known cardiovascular disease is no useful prognostic marker for MACE. Detection of carotid atherosclerosis by OPGs in these patients therefore has no clinical consequence.

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.

New stents for SFA.

Endovascular stent implantation was introduced to femoropopliteal procedures almost two decades ago. Initial results with balloon-expandable stainless steel stents and self expanding Elgiloy stents, however, were disappointing. In particular, recurrence rates after long-segment femoropopliteal stenting were rather high, in the range of 60% to 80% at 1 year. After years of stagnation, recent developments in femoropopliteal stent technology have been promising. Self-expanding nitinol stents have been evaluated in several prospective studies. Initial problems with stent fractures seem to be resolved using second-generation devices. The second generation of Nitinol stents have an enhanced flexibility particularly also in axial direction due to a reduction of cell interconnections and a more spiral orientation of the interconnections. However, until now there is no proof of any impact of the stent design on restenosis rate. Otherwise, stenting has been shown to be beneficial compared to balloon angioplasty especially in longer femoropopliteal lesions. The superior fracture resistance of the latest stent generation in combination with the production of long nitinol stents of up to 20 cm in length allow that more difficult and complex lesions can be treated endovascularly. The main unresolved problem with femoropopliteal stenting is the treatment of instent restenosis. Future concepts to further improve long-term patency after femoropopliteal stenting are therefore under investigation, including drug-eluting stents (DES), biodegradable stents, and coated stent-grafts. Stent grafts appear to be a viable option for the treatment of complex superficial femoral artery lesions, with comparable outcomes to prosthetic above-knee femoropopliteal bypass surgery. Concerning DES, we have to wait for the results of the ongoing studies.

Renal artery stenosis predicts adverse cardiovascular and renal outcome in patients with peripheral artery disease.

BACKGROUND: Patients with symptomatic peripheral artery disease (PAD) are considered cardiovascular high-risk patients. Our aim was to investigate whether incidental renal artery stenosis (RAS) increases the risk for adverse cardiovascular and renal outcomes in these patients. MATERIALS AND METHODS: We prospectively enrolled 487 consecutive patients admitted for revascularization of symptomatic PAD and performed a renal overview angiogram categorizing RAS as absent (0-29%), moderate (30-59%) and severe (>or= 60%) respectively. Clinical follow-up was for median 15 months (IQR 12-22) for the occurrence of major adverse events [MAE: composite of death, myocardial infarction (MI), stroke, percutaneous coronary intervention, coronary bypass surgery, amputation and kidney failure]. Glomerular filtration rates (GFR) were obtained at 12 months to quantify the course of renal function. RESULTS: A severe RAS was found in 76 patients (15.6%). Overall MAE occurred in 121 patients (24.8%), the composite endpoint of MI, stroke, amputation and death occurred in 101 patients (20.7%). Patients with a severe RAS had a 1.87-fold increased adjusted risk for MAE (95% CI 1.12-3.12, P = 0.017), a 2.51-fold increased adjusted risk for occurrence of the composite endpoint of MI, stroke, amputation and death (95% CI 1.45-4.34, P = 0.001) and a 2.93-fold increased risk for death (95% CI 1.41-6.08, P = 0.004), compared to those of patients without RAS respectively. We observed a significant association between the decrease of GFR over the 12-month follow-up period and the severity of RAS by multivariable analysis (P = 0.044). CONCLUSION: Severe RAS in patients with symptomatic PAD is an independent predictor of major adverse cardiovascular events, adverse renal outcome and mortality.

Critical limb ischaemia.

Critical limb ischaemia (CLI) is a manifestation of peripheral arterial disease (PAD) that describes patients with chronic ischaemic rest pain, or patients with ischaemic skin lesions, either ulcers or gangrene. The clinical diagnosis of CLI should be confirmed by haemodynamic parameters such as the ankle- or toe systolic pressure. The estimated annual incidence of CLI ranges between 500 and 1 000 new cases per 1 million, with diabetes being the most important risk factor. CLI is also a marker for mostly generalized and severe atherosclerosis, and therefore the prognosis of patients is poor concerning overall survival. The primary goals of treatment in patients with CLI are to relieve ischaemic pain, heal ulcers, prevent limb loss, improve patient function and quality of life and prolong overall survival. Any kind of revascularization should be done whenever technically possible, and therefore most patients should be referred to a vascular center. Furthermore, in patients with CLI a multidisciplinary approach is recommended to control pain, cardiovascular risk factors and other co-morbid disease. In patients with CLI not eligible for arterial revascularization, prostanoids are the only vasoactive drugs with proven efficacy. The safety and efficacy of the various forms of therapeutic angiogenesis still have to be proven before one can conclude on its role as an additional limb saving strategy.

Matching carotid anatomy with carotid stents.

Carotid artery stenting (CAS) has emerged as a promising minimal invasive treatment alternative to carotid arterectomy for patients with symptomatic and asymptomatic carotid artery stenosis. Complication rates of CAS continuously decreased during recent years. Operator experience and technical improvements equally contributed to the improved safety of the procedure. Today, devices specifically designed to fit the requirements of carotid interventions are available and allow a lesion-tailored interventional strategy. The choice of stents seems to play an important role in achieving optimal outcomes with the endovascular technique. Basically, three major types of stents are currently available: open cell nitinol stents, closed cell nitinol stents, and closed cell Elgiloy stents. The concept of cell design has implications on plaque coverage, but also on mechanical properties of the devices and conformation to carotid anatomy. The present review discusses the concept of lesion-tailored stenting to optimize early and late outcomes after CAS.

Peripheral arterial occlusive disease.

This article updates the diagnostic and therapeutic management of patients with peripheral arterial disease.

Non-randomized, prospective, multi-centre evaluation of the ABSOLUTE .035 peripheral self-expanding stent system for occluded or stenotic superficial femoral or proximal popliteal arteries (ASSESS Trial): acute and 30-day results.

AIM: The aim of the paper was to investigate the performance of the ABSOLUTE .035 Peripheral Self-Expanding Stent System in preventing restenosis of superficial femoral or proximal popliteal arteries. Due to a lack of large controlled trials proving its long-term durability femoropopliteal artery stenting is still a matter of debate. In this paper we report the study design, the acute and short-term results of a prospective European registry on the treatment of TASC B and C femoropopliteal lesions with the use of the ABSOLUTE stent. METHODS: This prospective, non-randomized, multi-centre study enrolled 122 patients with symptomatic peripheral occlusive disease at 14 sites in Europe. Patients were included with obstructed femoropopliteal arteries. Key inclusion criteria were de novo lesions > or = 4.0 mm and < or = 7.0 mm in diameter, and > or = 40 mm and < or = 200 mm in length. Single target vessel treatment had to be performed with a maximum of three stents. RESULTS: Mean target lesion length was 108 +/- 44 mm (range 22.2 to 200 mm) and mean reference vessel diameter 4.6 +/- 0.8 mm by quantitative angiography; 71% of the lesions analyzable by quantitative angiography (QA) had total occlusions. A total of 227 stents were implanted, 224 of which were deployed successfully (98.7%). Mean percentage of diameter stenosis was reduced from 90.9 +/- 15.5 % (range 41.3 to 100) to 19.0 +/- 8.4% (range 2.3 to 41.5). Device and procedural success were 83.6% each whereas technical success reached 100%. Sixteen lesions had a > or = 30% residual stenosis post-procedure, 6 of them (37.5%) rated as being calcified. Eleven patients experienced major complications (9.1%) and 6 patients experienced minor complications (5%) within 30 days. Duplex ultrasound based 1-month restenosis rate was 9.3%. Target lesion revascularization (TLR) and target vessel revascularization (TVR) rates were 0.8% and 1.7%, respectively and amputation rate was 0.8%. Mean ankle-brachial index (ABI) at rest and after exercise increased significantly from baseline to 30 days follow-up by 0.63 +/- 0.20 to 0.94 +/- 0.17 and from 0.44 +/- 0.23 to 0.85 +/- 0.21, respectively (P<0.001 each). CONCLUSION: The treatment of TASC B and C femoro-popliteal lesions with use of the ABSOLUTE stent is safe and feasible. Short-term follow-up documents persistent improvement of hemodynamics. The 6- and 12-month data have to be awaited for further conclusions:

Endovascular stent implantation for treatment of peripheral artery disease.

Endovascular stent implantation is a rapidly emerging technology for treatment of arterial obstructions in the entire circulation. During recent years, several randomized studies evaluated the effects of stenting in lower limb arteries. We herein provide an overview on data of trials in the iliac and femoropopliteal vessel area discussing the benefits and limitations of endovascular stents. In the iliac arteries, midterm and long-term data from one randomized trial including analysis on patency, clinical outcomes, cost-effectiveness and quality of life indicate that balloon angioplasty with selective stenting remains the therapy of choice for endovascular revascularization. In the femoropopliteal arteries, balloon-expanding stents were not superior to balloon angioplasty for treatment of short lesions, and self-expanding nitinol stents also failed to show a beneficial effect in short lesions below 5 cm. However, including longer lesions, one randomized trial indicated a beneficial effect of nitinol stents in lesions with a median length around 10-12 cm. Further studies and longer follow-up intervals are needed to confirm these data. Meanwhile, balloon angioplasty with optional stenting also remains the recommended endovascular approach for the femoropopliteal segment.

Influence and interaction of diabetes and lipoprotein (a) serum levels on mortality of patients with peripheral artery disease.

BACKGROUND: Diabetes mellitus is a risk factor for early complications and mortality in patients with peripheral artery disease. Lipoprotein (a) [Lp(a)] is also suggested to be a marker of increased cardiovascular risk. We investigated the association and interaction between diabetes mellitus, lipoprotein(a) and mortality in high risk patients with peripheral artery disease (PAD). METHODS: We studied 700 consecutive patients [median age 73 years, interquartile range (IQR) 62-80, 393 male (56%)] with PAD from a registry database. Atherothrombotic risk factors (diabetes, smoking, hyperlipidaemia, arterial hypertension) and Lp(a) serum levels were recorded. We used stratified multivariate Cox proportional hazard analyses to assess the mortality risk at a given patient's age with respect to the presence of diabetes and Lp(a) serum levels (in tertiles). RESULTS: Patients with Lp(a) levels above 36 mg dL(-1) (highest tertile) and insulin-dependent type II diabetes had a 3.01-fold increased adjusted risk for death (95% confidence interval 1.28-6.64, P = 0.011) compared to patients without diabetes or patients with non-insulin-dependent type II diabetes. In patients with Lp(a) serum levels below 36 mg dL(-1) (lower and middle tertile), diabetes mellitus was not associated with an increased risk for death. CONCLUSION: Insulin-dependent type II diabetes mellitus seems to be associated with an increased risk for mortality in PAD patients with Lp(a) serum levels above 36 mg dL(-1). PAD patients with non-insulin-dependent type II diabetes, and patients with diabetes and Lp(a) levels below 36 mg dL(-1) showed survival rates comparable to PAD patients without diabetes.