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[European trial of PGE1 alpha cyclodextrin. Short-term vs. long-term therapy in intermittent claudication].

BACKGROUND: The efficacy, safety and cost of prostaglandin E1 (PGE1 alpha-ciclodestrina) 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 randomised, 20-week study. METHODS: The study has selected 120 patients (109 were included and 99 completed the study). The average total walking distance at inclusion was 65.5 +/- 8 m (range 20-109). Phase 1 was a 2-week run-in phase (no treatment) for both protocols. In LTP phase 2 was the main treatment phase. The treatment was performed with 2-hour infusions (60 micrograms PGE1 alpha-ciclodestrina, 5 days each week for 4 weeks. In phase 3 (4-week interval period) PGE1 alpha-ciclodestrina 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 two days with a 2-hour infusion (1st day: morning 20 micrograms, afternoon 40 micrograms; 2nd day 60 micrograms, morning and afternoon). The reduced dosage was used only at the first cycle to evaluate reduced tolerability or side effects. Full dosage (60 micrograms b.i.d.) was used for all other cycles. The same cycle was repeated at the beginning of weeks 4, 8, 12 (phase 3). The observation period was between weeks 12 and 20 (phase 4). For both protocols 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 plan was used in both groups. RESULTS: Intention-to-treat analysis indicated an increase in walking distance which improved at 4 weeks (101.5% in STP vs 78.3% in LTP), at 8 weeks (260.9% in STP vs 107.3% in LTP) and at 20 weeks (351% in STP vs 242% in LTP). Comparable increases in pain-free walking distance were observed in the two groups. No serious drug-related side effects were observed. Local, mild, adverse reactions were seen in 7% of the treated subjects in the LTP and 5% in the STP. The average cost of LTP was approximately 6.588 ECU; for STP the average costs was approximately 1881 ECU. The cost to achieve an improvement in walking distance of 1 m was 35.6 ECU with the LTP and 9.45 ECU with the STP (26% of the LTP cost; P < 0.02). For an average 100% increase in walking distance LTP cost was 1937 ECU vs 550 ECU with STP (P < 0.02). The cost of PGE1 alpha-ciclodestrina (including infusion and operative costs) was 25% of the total cost for LTP (24.9% for STP). CONCLUSION: In summary between-group-analysis favours STP considering walking distance and costs. Results indicate good efficacy and tolerability of PGE1 alpha-ciclodestrina treatment. With STP less time is spent in infusion and more can be spent in the exercise program. STP reduces costs, speeds up rehabilitation and may be used in a larger number of non-specialised units available to follow the protocol.

Alprostadil↗

Measuring the rate of change of haemodynamic response at the onset of exercise in normal limbs and those with intermittent claudication.

Patients with claudication have an inadequate haemodynamic response to exercise. Blood flow response will not only have a magnitude, but also a rate of change. There is scope for investigating these parameters, as manipulation of the factors which control them may benefit work to improve the treatment for claudication. This work compares the responses for patients with one normal limb and one with intermittent claudication. A custom-built ergometer allows unilateral, infragenicular plantar flexion exercise, whilst common femoral artery blood flow can be measured continuously by Duplex ultrasound. This apparatus was used to measure blood flow before, at the onset of and during a 5 W square-wave exercise stimulus in 15 patients. The claudicant group had a mean steady-state gain that was approximately half that of the normal group at around 170 ml min(-1) (p < 0.001) and a response time that was much shorter (p = 0.006). A mean response time of 21.0 +/- 1.4 s was achieved in claudicant limbs compared to 31.8 +/- 2.9 s in normals. However, the average rate of change of blood flow during this response time was estimated to still be greater for the normal group, at 431.7 +/- 47.1 ml min(-2), than for the claudicant group. The differences in magnitude and rate of change of limb blood flow response to exercise in claudicants were significant and may have implications for the treatment of claudication.

Adaptation, Physiological↗

Leg blood flow and long-term cardiovascular prognosis in men with typical and atypical intermittent claudication.

OBJECTIVES: To compare leg blood flow and the long-term cardiovascular prognosis in men with typical and atypical intermittent claudication (IC) according to Rose's questionnaire. METHODS: Leg blood flow during reactive hyperaemia was assessed at 55 years of age by calf plethysmography. Measurement of the systolic ankle-arm pressure index was used to assess the prevalence of peripheral arterial disease (PAD) at 68 years of age. Mortality and incidence of cardiac events is based on record linkage with regional and national registers. RESULTS: Twenty-one (3%) out of 700 men had typical IC at 55 years of age. Sixteen (76%) of these had normal plethysmography, with a mean peak flow (95% CI) of 24.6 (19.3-30.0) ml/min/100 ml. Peak flows were similar and normal in men with atypical IC (mean 22.5; 95% CI 21.3-23.6) and men having no pain (mean 23.8; 95% CI 23.1-24.4). Mortality rates were increased in men with typical IC but who had normal leg blood flow (49.5 deaths/1000 person years; p = 0.008), and men having atypical IC (35.3 deaths/1000 person years; p = 0.007) in comparison with men having no leg pain (27.4 deaths/1000 person years). This could not be accounted for by an increased cardiac event rate. The prevalence of PAD at 68 years of age was not increased in either of these two groups. CONCLUSIONS: Only 12% of subjects with exertional pain fulfilled all criteria for typical IC. Typical and atypical claudication in absence of objective evidence of PAD was associated with a reduced life expectancy, but not with an increased cardiovascular risk. To properly assess the prognosis, non-invasive assessment of PAD should be used in addition to questionnaires.

Aged↗

Hyperhomocyst(e)inaemia: an independent risk factor for intermittent claudication.

The aim of this study was to test the question of hyperhomocyst(e)inaemia as a risk factor for intermittent claudication (IC) independent of other important risk factors for peripheral atherosclerotic disease, such as smoking, hypertension, diabetes mellitus, hypercholesterolaemia, hypertriglyceridaemia, low levels of high-density-lipoprotein (HLD) cholesterol and age. The study population was recruited from an epidemiological study in Linköping County, Sweden, where all middle-aged men (n = 15,253, 45-69 years of age) were screened for IC. Seventy-eight subjects with verified IC and 98 healthy sex- and age-matched controls were randomly selected. Plasma levels of homocyst(e)ine (including the sum of free and bound forms of homocysteine and their disulphide oxidation products, homocystine, and homocysteine-cysteine mixed disulphide) were significantly higher (16.74 +/- 5.45 mumol l-1, mean value +/- SD, P = 0.0002) in IC subjects than in controls (13.80 +/- 3.21 mumol l-1), with 23% of the claudicants above the 95th percentile for controls. Stepwise logistic regression analysis revealed that the difference in plasma homocyst(e)ine was independent of the other above-mentioned risk factors. Moreover, the elevation of plasma homocyst(e)ine in claudicants was mainly confined to subjects with serum folate levels of less than or equal to 11.0 nmol l-1. The results suggest that folic acid supplementation should be tried in IC subjects with hyperhomocyst(e)inaemia.

Aged↗

The relationship between glycogen content of leg muscles and working capacity in patients with intermittent claudication.

The relationship between the glycogen content of the vastus lateralis muscle and the working duration was determined in 6 patients with intermittent claudication. The working duration was determined on a bicycle ergometer at a load of 450 kpm/min. Muscle glycogen was determined in percutaneous needle biopsy specimens. The resting glycogen content in the vastus muscle increased significantly after depletion of the stores by physical exercise followed by glucose feeding for 2 days. This increase was associated with an increased working duration. This improvement of the working duration connected with high muscle glycogen content was a temporary phenomenon. When the duration was measured shortly after exercise, i.e. after depletion of the glycogen stores it was reduced to the preexperimental level. The improved working duration associated with increased glycogen content of leg muscles did not seem to be related to the improved walking capacity in claudication patients after physical conditioning.

Aged↗

[Influence of interval training on the physical capacity and peripheral circulation in patients with intermittent claudication].

Physical performance on treadmill and calf blood flow (venous occlusion plethysmography) were determined in 6 patients with symptoms of intermittent claudication before and after a 10-weeks period of intervall training. Arteriosclerotic occlusions of femoral artery were proved on arteriography in all cases. After training, a significant improvement of the claudication distance and the work performed on the treadmill on an average of 44% were stated, whereas nnd. The peripheral blood flow at rest and after 3 minutes circulatpressed as area under the blood flow curve during reactive hyperaemia) on an average of 54%. The benefits of a controlled home-training program as the necessity of investigation at maximal stress, when assessing the haemodynamic effects of physical training, are pointed out.

Aged↗

An evaluation of patients with severe intermittent claudication and the effect of treatment with naftidrofuryl.

A randomized placebo-controlled study was undertaken in 188 patients with severe intermittent claudication attending two vascular clinics in Manchester and Liverpool. After a 4-week run-in period, patients received active or placebo treatment for 24 weeks. Patients were assessed on a treadmill prior to the 4-week run-in period, at randomization, and at 8, 16, and 24 weeks. Outcome was measured in terms of change in pain-free walking distance, maximum walking distance, and pressure indices. In this severe claudication population, in which the patients presented with a mean pain-free walking distance of 60 m, an intention-to-treat analysis demonstrated that the outcome in the naftidrofuryl-treated group was significantly better than in the group receiving placebo (p = 0.045). Additionally, 7% of patients in the naftidrofuryl group deteriorated compared with 22% in the placebo group (p = 0.005). Of the various risk factors that were recorded during the study--smoking habits, the presence of hypertension, diabetes, obesity, and duration of illness--only duration of illness had a significant influence on outcome. Maximum walking distances alone were not significantly influenced by treatment, but the use of a combined index of pain-free walking distance, maximum walking distance, and pressure indices to record success or failure confirmed a significant treatment effect (p = 0.047). A higher incidence of minor gastrointestinal symptoms was recorded in the naftidrofuryl-treated group. Treatment with naftidrofuryl was shown to prevent or slow the deterioration observed in a group of patients with severe claudication over a 24-week period.

Adult↗

[A new clinical entity: "the algodystrophic intermittent claudication of the lower limbs syndrome" (author's transl)].

A new clinical entity is proposed by the authors, "the algodystrophic intermittent claudication of the lower limbs syndrome", characterised by diffuse pains in the foot, having neither a constrictive nature, nor a radicular distribution. The pain appears after walking a certain distance, forcing the patient to stop, and reappears when he starts to walk again. Bone isotopic examinations and repeated radiographic investigations should be conducted when confronted with such a clinical syndrome in order to confirm the diagnosis of algodystrophy. In view of the polymorphic nature of this affection, it is not surprising that new clinical aspects can still be described at the present time.

Arteritis↗

Personality factors as predictors of compliance with and the outcome of supervised self-care program for patients with intermittent claudication.

Personality factors related to the outcome of supervised self-care treatment program were studied in 56 patients with intermittent claudication. Psychological methods used were: structured interviews, the Rorschach Test, the Thematic Apperception Test, Beck's Depression Inventory, the Beth Israel Hospital Inventory of alexithymic behavior and Sauri's Creativity Inventory of psychic flexibility and adaptability. The patients who had no apparent signs of psychic disorders and were also capable of coping with disease-related psychic problems showed the best recovery. Alexithymic patients with a low level of psychic adaptability were likely to find the supportive relationship rewarding, but optimal recovery was not achieved. The results indicated that paranoid tendencies may be obstacles to a satisfying doctor-patient relationship and should be controlled.

Adult↗

Is it possible to reduce the risk of cardiovascular events in subjects suffering from intermittent claudication of the lower limbs?

This study meta-analysed randomized, double-blind, placebo controlled trials in patients with intermittent claudication of the lower limbs comparing ticlopidine to placebo in order to test the hypothesis that the drug, a pure antiplatelet agent, is able to reduce the incidence of thrombotic cardio-vascular events on atherosclerotic arteries in these patients. A highly significant reduction, from 9% to 3% (p ranging from 0.006 to 0.002), was observed for fatal or non-fatal cardio-vascular events in a total of 611 patients (301 with ticlopidine, 310 with placebo). The duration of follow-up ranged from 6 to 12 months. Side-effects, defined as withdrawal from study medication for any reason but death, cardio-vascular events or cancer, were 2.4 times more frequent in the ticlopidine treated patients as compared to placebo. We concluded that in this high risk population, prevention of cardio-vascular events is likely to be effective.

Cardiovascular Diseases↗

Leg blood flow in intermittent claudication--a comparison between non insulin dependent diabetics and non diabetics.

The influence of diabetes on leg blood flow in intermittent claudication has been assessed by comparing the systolic arm-ankle pressure gradient at rest and resistance to blood flow during reactive hyperemia in patients with non-insulin dependent diabetes and non-diabetic controls. Cases and controls were matched for age and sex. Smoking habits, blood pressure, and blood lipids didn't differ in the two groups. Diabetes was associated with a higher resistance to blood flow during reactive hyperemia and a greater arm-ankle pressure gradient at rest. Resistance to blood flow during reactive hyperemia was in the non-diabetics strongly correlated to the arm-ankle pressure gradient at rest (r = 0.84). Corresponding correlation coefficient was in diabetics 0.04. In one of four diabetic legs a high resistance to blood flow during reactive hyperemia didn't correspond to a big arm-ankle pressure gradient. The results in this study support the concept of both macro- and microvascular disease in diabetes.

Adolescent↗

[Cystic adventitial degeneration of the popliteal artery; an unexpected cause of intermittent claudication].

Three men, aged 48, 44 and 51 years, were referred to the vascular surgery outpatient clinic because of acute intermittent claudication in one leg. The first patient had no medical history and no vascular risk factors, the second patient was receiving drug treatment for hypercholesterolaemia and diabetes mellitus and the third patient smoked. After additional radiological diagnostics, cystic adventitial degeneration of the popliteal artery was diagnosed in all patients. All 3 patients were operated. Only circumferential resection of the cystic adventitia and the outer layer of the media, so-called exarteriectomy, was performed in the second patient. The other 2 patients underwent resection of the affected popliteal artery followed by an autologous vein graft. The post-operative course was uncomplicated. The diagnosis of cystic adventitial degeneration was confirmed histopathologically. Cystic adventitial degeneration is localised only in the popliteal artery in 85-90% of cases. It is probably caused by incorporation of mesenchymal cells in the wall of the popliteal artery during embryogenesis. The disease is often progressive and, if left untreated, may lead to critical ischaemia due to arterial occlusion. Surgical intervention is therefore necessary, with exarteriectomy as the preferred technique, especially because the patients are often young.

Adult↗

Effect of propionyl-L-carnitine on quality of life in intermittent claudication.

A double-blind, dose titration study was designed to assess the efficacy of propionyl-L-carnitine in intermittent claudication. The effect on walking capacity was described in a previous article. This study reports on the effect on quality of life, assessed by the McMaster Health Index Questionnaire (MHIQ). After 24 weeks of treatment, the global MHIQ score did not show any difference from baseline in patients randomized to placebo (n = 102). Conversely, it increased from 0.59 +/- 0.12 to 0.64 +/- 0.12 in those taking propionyl-L-carnitine (n = 85). Analysis of variance showed a significant difference between treatments (p = 0.018). Stepwise multiple regression analysis identified baseline maximal walking capacity (cutoff point 250 m) as a predictor of treatment outcome. In patients walking < 250 m, propionyl-L-carnitine significantly improved physical function (p = 0.027), emotional function (p = 0.002), and global MHIQ score (p = 0.002) compared with placebo. Also, for maximal walking capacity, group difference significantly favored propionyl-L-carnitine (p = 0.009). In patients with baseline maximal walking capacity > or = 250 m, propionyl-L-carnitine did not affect the MHIQ scores, nor improve walking performance. These data indicate that propionyl-L-carnitine exerts beneficial effects on quality of life and walking performance in patients with more severely limited walking capacity.

Aged↗

The effect of superficial femoral artery occlusion on the outcome of aortofemoral bypass for intermittent claudication.

This study was undertaken to evaluate the effects of untreated superficial femoral artery occlusion in patients undergoing aortofemoral bypass for intermittent claudication. In 56 patients at a mean follow-up time of 3.3 years, graft patency, treadmill walking tolerance, and ankle systolic pressure indices (ASPI) were compared in two groups of limbs: those with a patent superficial femoral artery and those with that vessel occluded. There was a high graft patency rate with no significant difference between the two groups. In limbs with a patent superficial femoral artery, 86% were completely relieved of claudication. However, in limbs with an occluded superficial femoral artery, only 26% were relieved of claudication. In limbs with a patent superficial femoral artery, the mean postoperative ASPI was 0.87 (SE +/- 0.22) compared with 0.61 (SD +/- 0.17) in limbs with an occluded superficial femoral artery. These results indicate that, in patients with combined superficial femoral artery occlusion and aortoiliac disease, revascularizing the deep femoral artery by aortofemoral grafting often does not achieve relief of claudication. There is a need for more effective hemodynamic discrimination of the relative contribution of proximal and distal occlusions.

Aorta, Abdominal↗

Exercise: the best therapy for intermittent claudication?

The prophylactic value of physical activity for arteriosclerotic diseases is generally accepted. Regular exercise is also the most effective therapy for intermittent claudication although drug treatment is more popular in general practice. Recent findings show that exercise and drug treatments complement each other.

Arterial Occlusive Diseases↗

Continuous electrocardiography recording at examination of walking capacity in patients with intermittent claudication.

A treadmill test with increasing "walk-work" load and continuous electrocardiographic monitoring has been used in 245 patients with intermittent claudication. It was found that many patients underestimated their walking capacity. No good correlation was obtained between the observed walking capacity and the systolic blood pressure in the toes. Pathological electrocardiograms were found at rest in 36 per cent of the patients. Additional pathological ecg-reactions indicative for ischaemic heart disease appeared during the tests in 34 percent of the patients. Around 10 per cent of the tests had to be interrupted because of threatening ecg changes.

Aged↗

Ticlopidine in the treatment of intermittent claudication: a 21-month double-blind trial.

After a 3-month, single-blind, run-in period, 151 patients with intermittent claudication were randomly allocated to receive the antiplatelet agent ticlopidine (250 mg twice per day) or an identical placebo. One hundred and twenty patients completed the double-blind phase of the trial, which lasted 21 months. The primary analysis was performed according to the "intention-to-treat principle" in all 151 enrolled patients. There was, continuing on from the third month after randomization, a progressive and sustained improvement of the pain-free and maximum walking distances in the two treatment groups that was significantly greater in the ticlopidine group. The ankle-arm systolic blood pressure ratio at rest and after exercise increased in a significant manner in the ticlopidine group only. In a secondary analysis, with exclusion of 25 patients because of protocol violations at selection, consistently significant differences in favor of the ticlopidine group were still observed for maximum walking distance and systolic ankle-arm blood pressure ratio, both at rest and after exercise. No major side effects were reported in the treated group. It is concluded that long-term treatment with ticlopidine improves walking ability and ankle systolic blood pressure in patients with claudication.

Blood Pressure↗

[Effects of the Tibetan herbal preparation Padma 28 in intermittent claudication].

In a placebo-controlled double blind study the effect of Padma 28, a Tibetan herbal prescription, on patients with intermittent claudication was investigated. After two weeks without vasoactive therapy 23 patients were treated by Padma 28 and 20 by placebo. The patients had a disease history of at least 8 months, a steady state for symptoms (maximum walking distance below 250 m), and were distributed randomly in the two groups. After 16 weeks the patients treated with Padma 28 exhibited on standardized ergometry an increase of some 100% (p less than 0.01) in the maximum as well as painfree walking distance. The control patients showed increases of 21% in maximum (p less than 0.05 as compared to Padma 28), and 46% in painfree walking distance. The drug was well tolerated and no drop-out ensued because of side effects.

Clinical Trials as Topic↗