The efficacy and safety of a coumarin-/troxerutin-combination (SB-LOT) in patients with chronic venous insufficiency: a double blind placebo-controlled randomised study.

BACKGROUND: The objective was to evaluate the oedema-protective effect of a vasoactive drug (coumarin/troxerutin [SB-LOT]) plus compression stockings in patients suffering from chronic venous insufficiency after decongestion of the legs as recommended by the new guidelines. PATIENTS AND METHODS: 231 patients were randomly assigned medical compression stockings plus SB-LOT (90 mg coumarin and 540 mg troxerutin per day) or medical compression stockings plus placebo for the first 4 weeks and SB-LOT or placebo for the second 12 weeks of the study. The primary efficacy endpoint was the lower leg volume measured by well-established water plethysmometry. RESULTS: 226 patients were evaluated. After ceasing compression stockings, an edema protective effect was detected in the SB-LOT-group but not in the controls. Recurrence of leg volume increase was by 6.5 +/- 12.1 ml and by 36.7 +/- 12.1 ml in the SB-LOT and placebo group, respectively (p = 0.0402). The local complaint score and general aspects of quality of life were also superior for the SB-LOT-group (p = 0.0041). Significant differences were also observed with regard to clinical global impression and therapeutic effect. No serious adverse drug reaction or clinically relevant impairment of laboratory parameters occur. CONCLUSION: This study confirms the oedema-protective effect of SB-LOT in chronic venous insufficiency and provides a treatment option for patients who discontinue compression after a short time.

Findings of the Naftidrofuryl in Quality of Life (NIQOL) European study program.

BACKGROUND: We report in this paper the findings of a pooled analysis of 3 previously published studies undertaken in Germany, France and Belgium to assess the effects of naftidrofuryl on the quality of life of patients with intermittent claudication. METHODS: A total of 754 patients were randomised in the 3 studies, 709 of whom (358 naftidrofuryl, 351 placebo) were available for the primary intention-to-treat analysis. The primary outcome variable was the change in the disease-related limitation of the quality of life as measured by the CLAU-S questionnaire. This instrument which has been validated in an international study, comprises 47 questions covering 5 dimensions: "daily living", "pain", "social life", "disease specific anxiety" and "mood". RESULTS: A multivariate analysis of covariance adjusted for baseline values, study effect and first order study treatment interaction, demonstrated the global superiority of naftidrofuryl over placebo (p<0.001). A separate covariance analysis for the 5 dimensions showed highly significant differences for "daily living", "pain", "social life" and "mood" (all p<0.01). CONCLUSIONS: In conclusion, this pooled analysis has shown that naftidrofuryl can significantly improve the quality of life of patients with intermittent claudication. These findings, taken together with evidence from previous studies that it improves treadmill walking distances, suggest that naftidrofuryl can play a useful role in the treatment of this condition.

[Stage-adapted therapy concept in ascending thrombophlebitis]. / Stadiengerechtes Therapiekonzept bei aszendierender Varikophlebitis.

Varicophlebitis is the most frequent and important acute complication of a varicosed long and/or short saphenous vein. In view of the controversial discussion about the either conservative or surgical treatment, a clinically relevant classification of this syndrome appears useful: Stage I includes varicophlebitis without involvement of the respective junctional valve--in the groin or at the knee--and deep veins. While in Stage II the proximal part of the thrombus has reached the respective junctional valves of the long or short sapheneous vein, in Stage III it has entered the deep veins by means of these valves. In Stage IV the thrombus migrates via insufficient perforating veins into the deep system. Stages I and IV should be treated conservatively first, removal of the varicous veins should be performed after regression of the acute symptoms. Stages II and III should be considered an indication for urgent surgery. The surgical strategy consists of crossectomy, resection of the saphenous vein without stripping, radical excision of all varicous veins and ligature of insufficient perforating veins. In stage III the thrombectomy of the deep veins using the Fogarty-procedure must be carried out before any other measures are taken. In 1996 a total number of 40 limbs with ascending varicophlebitis (stage I = 16, stage II = 19, stage III = 5) was observed. 10 extremities (stage I = 2, stage II = 5, stage III = 3) underwent surgical treatment. 1 patient developed a deep infection of the groin, the average stay in hospital was 9 days.

[Angina abdominalis: duplex ultrasound diagnosis and percutaneous revascularization]. / Angina abdominalis: duplexsonographische Diagnostik und perkutane Revaskularisierung.

Intestinal ischemia is still a challenge for clinicians and requires a close interdisciplinary cooperation between internist, surgeon and radiologist. In the last years the diagnosis and therapy, classically invasive and surgical, was supplemented by duplex ultrasound and percutaneous techniques like angioplasty and stenting. A 56 year-old man from Greece presented with epigastric pain, which was intensified by food ingestion. These symptoms were caused by a stenosis of the superior mesenteric artery, which was diagnosed by duplex sonography and angiography. No blood flow was detected in the inferior mesenteric and the celiac artery. Occlusion of one internal carotid artery made the patient a poor candidate for surgery. Therefore an interventional approach was chosen. A good result was achieved by angioplasty and stent implantation. On the day after the intervention oral food intake was possible without any pain. 18 months after the intervention the patient was free of abdominal symptoms. Therapy of mesenteric ischemia by percutaneous angioplasty and stenting is published only in case-reports and small series. Therefore the indication is mainly restricted to patients with a high risk for a surgical intervention.

Endoluminal repair of peripheral arterial aneurysms: 4-year experience with the cragg endopro system I.

PURPOSE: To assess the efficiency and long-term patency of the Cragg EndoPro System I in patients with peripheral arterial aneurysms. MATERIALS AND METHODS: In 10 patients, 13 stent-grafts were used to treat 15 arterial aneurysms. Aneurysms were located in the common iliac (n = 4), superficial femoral (n = 4), popliteal (n = 3), and subclavian arteries (n = 2), and in a femoropopliteal bypass-graft (n = 2). Follow-up ranged between 2 and 46 months (mean, 36 months). Examination included clinical status, color-coded duplex sonography, computed tomography angiography, and intra-arterial digital subtraction angiography (DSA). RESULTS: Technical success was achieved in all patients. Primary patency was four of four in iliac vessels and three of nine in non-iliac vessels; secondary patency in noniliac vessels was four of nine. Repairs included one local lysis, four percutaneous transluminal angioplasties, one surgical thrombectomy, and one bypass surgery. Stent wire disintegration was detected in one of four iliac stent-grafts and in seven of nine noniliac stent-grafts. In noniliac grafts, significant stenoses occurred in three of nine; occlusion occurred in five of nine. One complication at the iliac level was a vessel wall penetration at the proximal stent edge, with development of a new aneurysmal formation. No late endoleaks were found. CONCLUSION: Exclusion of peripheral arterial aneurysms with stent-grafts is feasible. Long-term results are excellent in iliac vessels. Mechanical weakness of the stent assembly and frequent re-stenoses or occlusions are significant drawbacks in noniliac vessels with low patency rates.

Influence of folic acid, pyridoxal phosphate and cobalamin on plasma homocyst(e)ine levels and the susceptibility of low-density lipoprotein to ex-vivo oxidation.

Mild hyperhomocyst(e)inaemia is a risk factor for atherosclerotic vascular disease. In-vitro studies have shown that autooxidation of homocyst(e)ine is accompanied by the generation of oxygen radicals. This may lead to oxidative modification of low-density lipoproteins (LDL) and promote atherosclerotic vascular lesions. In male patients with peripheral arterial occlusive disease we determined fasting and post methionine load homocyst(e)ine levels by high performance liquid chromatography and the susceptibility of their LDL particles to ex-vivo oxidation by continously measuring the conjugated diene production induced by incubation with copper ions. Oxidation resistance (expressed as lag time), maximal oxidation rate, and extent of oxidation (expressed of total diene production) of LDL from patients with normal or mildly elevated homocyst(e)ine levels did not differ significantly. Folic acid, pyridoxal phosphate and cobalamin supplementation significantly decreased plasma homocyst(e)ine levels in hyperhomocyst(e)inaemic patients. This went along with a significant decrease in the extent of LDL oxidation and additionally increased HDL-cholesterol levels. The clinical relevance of these findings for the long-term course of atherosclerotic vascular disorders has to be determined by intervention studies.

Naftidrofuryl can enhance the quality of life in patients with intermittent claudication.

BACKGROUND: Using a disease specific questionnaire, the CLAU-S, we undertook a double blind, placebo controlled study in patients with intermittent claudication to determine whether the increase in the pain-free walking distance, previously demonstrated with naftidrofuryl, is reflected as an improvement in the patients' quality of life. PATIENTS AND METHODS: 287 patients, with stable intermittent claudication for at least 3 months were entered into the study. Following an initial one month placebo run-in, patients were randomised to either naftidrofuryl, at a dosage of 200 mg three times daily, or matching placebo, for 6 months. All patients completed the self-administered CLAU-S questionnaire which is divided into 6 dimensions, before the start of treatment, at 3 and 6 months. Statistical analysis was undertaken on an intention-to-treat (ITT) basis which included all patients know to have taken at least one dose of the drug and to have provided key data on at least one occasion after baseline. For each of the CLAU-S dimensions the two groups were compared with respect to difference between the initial and final values. RESULTS: 255 patients (133 naftidrofuryl, 122 placebo) were eligible for the ITT analysis. Significant improvements, in favour of the active medication, were seen for the dimensions "daily living", "pain", "disease specific anxiety" and "mood". A multivariate analysis of covariance, which took into account such factors as initial score, age and sex confirmed the global superiority of naftidrofuryl (p = 0.004). CONCLUSIONS: In this placebo controlled study, using a disease specific questionnaire, naftidrofuryl has been shown to significantly improve several aspects of the quality of life of patients with intermittent claudication.

[Carotid bruit: what should be done? Color duplex ultrasound indicates if operation is necessary]. / Karotisgeräusch: was tun? Farbduplex-Sono verrät, ob eine Operation notwendig ist.

Carotid bruits need to be investigated without delay. The best imaging procedure available is color-coded duplex ultrasonography in the hands of an experienced examiner. Intra-arterial digital subtraction angiography should be used only when a surgical option appears indicated and the surgeon requests it prior to the operation. Determination of the intima/media thickness with the aid of the B scan provides good prognostic information. In the case of higher-grade stenoses with corresponding symptomatology, carotid surgery is indicated. Before carrying out such operations, however, the patient's risk and the surgery-related risk of a stroke or some other event occurring must be carefully weighed, one against the other, with the results achieved by the surgeon in this area being a major factor.

[Venous thrombosis--a diagnostic and therapeutic challenge]. / Venöse Thrombosen--eine diagnostische und therapeutische Herausforderung.

PURPOSE: Venous thrombosis and embolism has been the target of intensive investigation in recent years. The growing importance of mortality and morbidity due to venous thromboembolism led to new diagnostic and therapeutic tools. The clinical diagnosis may be misleading and both false-negative and false-positive diagnoses are common, when only clinical signs and symptoms are considered. METHODS: A major problem in the care of the patient is to establish the correct diagnosis. Studies show, that only Venography or Duplexsonography can clearify diagnosis. Risk factors for venous thromboembolism, propability calculations and consensus recommendations for diagnosis and therapy are presented. RESULTS: Diagnosis. Diagnosis of deep vein thrombosis must be established by Duplexultrasound and/or venography. Special situations may need further investigation by CT-scan or NMR-tomography. No single clinical sign or combination of signs give enough sensitivity and specificity. In patients with thromboembolism without clear etiology, hypercoagulability, neoplasms, compression syndroms, vascultides and other conditions have to be excluded. THERAPY: Heparins are the standard-therapy. Low-molecular weight heparins may have some benefits over standard heparins in terms of side effects and handling. Coumarin therapy can be started immediately, if no invasive procedures are necessary and have to be continued for 4-12 months, in recurred events and/or hypercoagulability even life-long. Thrombolysis is restricted to very few patients (patients under the age of 50 with large thrombosis not older than 3-7 days and no contraindications). Surgical thrombectomy is even more restricted. Compression therapy should be obligatory in all patients with thromboembolism. CONCLUSIONS: Thromboembolism is mainly a diagnostic challenge. The immediate start of the appropriate treatment may reduce embolism and thrombus formation, induce recanalisation and prevent post-thrombotic syndrom.

Blue toe syndrome after initiation of low-dose oral anticoagulation.

Cholesterol emboli are a known complication after arterial catheterization, arterial surgery, and after lysis with plasminogen activators. The clinical presentation of cholesterol emboli is variable ranging from a localized blue toe syndrome to a multisystem disease. The purpose of this case report is to report on a patient with blue toe syndrome and livedo reticularis occuring two months after initiation of low-dose oral anticoagulation with phenproucomon. The non-invasive studies revealed an infrarenal abdominal aneurysma lined by a thin wall thrombus as a potential source of cholesterol emboli. The patient had a benign course with resolution of toe pain after a period of four weeks, without development of an ulceration. The case report demonstrates that cholesterol emboli may also occur in patients treated with low-dose oral anticoagulation and no previous arterial catheterization.

Low-dose iloprost infusions compared to the standard dose in patients with peripheral arterial occlusive disease Fontaine stage IV. DAWID Study Group.

BACKGROUND: Intravenous iloprost, titrated from 0.5 up to 2.0 ng/kg/min has been shown in patients with PAOD III/IV to significantly improve healing of trophic lesions, relief of rest pain, and reduce the rate of major amputation or death at 6 months as compared to placebo. The effect is considered related to improvement of the microcirculation. The aim of the present trial was to identify an optimum dose regarding treatment response and tolerability, by studying 4 doses of 25, 50, 75 and 100 micrograms iloprost daily. PATIENTS AND METHODS: 302 patients with PAOD IV were randomised via a double-blind fashion to one of the 4 doses. The primary endpoint was the responder rate at end of treatment. Responders were defined as patients with very good or good global efficacy, as judged by lesion healing and pain relief. Side effects were documented and a pre-defined benefit/risk index was calculated. RESULTS: No dose-dependency of iloprost regarding primary or secondary endpoints was observed. The rate of responders ranged between 48.7-53.5%. Side effects, mainly related to vasodilation, increased dose-dependently (p < 0.001, chi 2-test), with a significant decrease of the benefit/risk index from 2.19 +/- 1.19 to 1.64 +/- 0.97 (p = 0.012, ANOVA). Responders had a better outcome at 6 months than non-responders (2.6 fold higher rate of major amputation or death; life table analysis). CONCLUSIONS: It is concluded that iloprost should be titrated to the optimum rather than maximum tolerated dose, since a higher incidence of side effects not associated with an increased treatment response was observed at higher doses.

Improvement in the quality of life after i.v. PGE1 therapy for intermittent claudication.

BACKGROUND: Increasingly and justifiably, clinical studies are now being expected to investigate the influence of therapeutic measures also on the quality of life of the patient. PATIENTS AND METHODS: Since no data on the variability of changes in the quality of life of the patient following PGE1 treatment are so far available, the initial investigation was designed as an uncontrolled pilot study. 104 patients (median age 64.5 years) with a maximum of walking distance on the treadmill (3 km/12%) of 50-250 m were included and given a daily intravenous infusion of 60 micrograms PGE1 (Prostavasin) over a period of 4 weeks excluding weekends. This was followed by a treatment-free follow-up period of 3 months. Changes in the quality of life were recorded with both the newly developed disease-specific questionnaire PAVK-86, and the generic questionnaire SF 36; in addition, the pain-free and maximum walking distances on the treadmill were also established prior to and immediately following treatment, as also at the end of the follow-up period. RESULTS: The quality of life was significantly improved in all dimensions (functional status, complaints, pain, mood, anxiety, social life, treatment expectations) in addition to a marked increase in the median pain-free walking distance from 77 to 108 m (p < 0.001) and the maximum walking distance from 118 to 171 m (p < 0.001). At the end of the 3-month observation period, the improvement was essentially still demonstrable. CONCLUSION: The study has shown for the first time that treatment with intravenous PGE1 brings about not only the already known increase in the walking distance, but also a clinically relevant and significant improvement in the patient's quality of life.

Efficacy of a new prostaglandin E1 regimen in outpatients with severe intermittent claudication: results of a multicenter placebo-controlled double-blind trial.

For the first time efficacy and safety of a new prostaglandin E1 (PGE1) regimen in the treatment of intermittent claudication were evaluated in a randomized, double-blind, placebo-controlled multicenter clinical trial. The study involved 213 outpatients with a maximum walking distance of 50 to 200 m measured on the treadmill (3 km/hr, 12% grade). After a 2-week run-in phase they received a 2-hour intravenous infusion of 60 micrograms PGE1 or placebo 5 days a week for 4 weeks. It was followed by a 4-week interval treatment with the same medication administered only twice a week. Patients were monitored for 3 months when they received no study medication. In the PGE1 group the intention-to-treat analysis (n = 208) revealed an increase in walking distance after 4 weeks of 75% (placebo, 43%). At the end of the interval treatment the walking distance had improved to 101% (placebo, 60%). The results remained virtually constant during follow-up (PGE1, 104%, placebo, 63%). Between-group comparisons showed significant differences in favor of PGE1 for all three time points of measurement (p < 0.05, p < 0.01, and p < 0.05). PGE1 was well tolerated; the rate of adverse reactions related to the treatment was 12.8% (placebo, 7.7%). In summary, these results show that the new PGE1 regimen is effective and safe in the treatment of outpatients with intermittent claudication.