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Sarpogrelate, a 5-hT2A receptor antagonist in intermittent claudication. A phase II European study.

This was a multinational, multicentre, double-blind Phase II study in Europe to evaluate the efficacy and safety of two dose regimens (200 mg bid and 200 mg tid) of sarpogrelate (MCI-9042, 5-HT2A receptor antagonist) compared to placebo in patients with stable, moderately severe intermittent claudication. Following a single-blind placebo run-in period of 6 weeks, 364 (309 male and 55 female) patients (59.2 +/- 8.4 years, mean +/- SD) were randomized to receive sarpogrelate 200 mg bid, 200 mg tid or placebo for 24 weeks with a follow-up of 8 weeks. The primary objective was the increase of absolute claudication distance (ACD) at the end of treatment (week 24) compared to placebo. Analysis of covariance (ANCOVA) was performed on the log-transformed percentage of baseline ACD: loge(ACD/baseline). A responder analysis (defined as a > or = 50% improvement in ACD) was also performed. There was a marked training/placebo effect on the ACD which persisted up to 16 weeks. At 24 weeks the primary objective did not reach statistical significance (200mg bid vs placebo, p = 0.225; 200mg tid vs placebo, p = 0.580). In the responder analysis, 200 mg bid showed a statistically significant difference vs placebo (p = 0.035). In the exploratory analysis with completers (patients completing all treadmill tests), there was a statistical difference in ACD/baseline change for 200 mg bid (p = 0.035) and in the responder analysis for 200 mg tid (p = 0.044) at 24 weeks compared to placebo. Both treatments showed a carry-over effect for ACD during the 8-week follow-up (weeks 28-32). The treatment was well tolerated and no clinically significant safety concerns were reported. In conclusion, the study results confirm that sarpogrelate is well tolerated and although the primary endpoint failed to reach statistical significance, the responder analysis showed an increased absolute walking distance, which makes a further trial warranted, including a larger population, and possibly also a longer treatment period.

Adult↗

Assessment of intermittent claudication: a comparison of questionnaire, visual analogue scale and subjective estimate information with post-exercise ankle-brachial pressure index.

In order to assess two simple methods of evaluation of claudication, a standard questionnaire and visual analogue scale, a comparison was made between them and the post-exercise pressure index used as a gold standard. Fifty-eight consecutive stable claudicants were recruited to the study, 51/58 having arterial insufficiency according to post-exercise pressure measurements. Both methods appeared to correlate rather poorly with post-exercise pressures. Thus visual analogue scale cannot be used alone to assess walking tolerance but as it offers qualitative information it may be used to supplement pressure measurements in the assessment of incapacity caused by intermittent claudication.

Adult↗

Effects of OP-1206 alpha-CD on walking dysfunction in the rat neuropathic intermittent claudication model: comparison with nifedipine, ticlopidine and cilostazol.

The systemic treatment effects of OP-1206 alpha-CD (17S-20-dimethyl-trans-delta 2-PGE1 alpha-cyclodextrin clathrate), a prostaglandin E1 (PGE1) analogue, on walking dysfunction, spinal cord blood flow (SCBF) and skin blood flow (SKBF) were assessed in the rat neuropathic intermittent claudication (IC) model in comparison with nifedipine (dimethyl 1,4-dihydro-2,6-dimethyl-4-(2-nitrophenyl)-3,5-pyridinedicarboxylate), ticlopidine (5-[(2-chlorophenyl)methyl]-4,5,6,7-tetrahydrothieno[3,2-C]pyridine hydrochloride) and cilostazol (6-[4-(1-cyclohexyl-1H-tetrazol-5-yl)-butoxy]-3,4-dihydro-2(1H)-quinolinone). Two pieces of silicone rubber strips were placed in the lumbar (L4 and L6) epidural space in rats. After surgery, walking function was measured using a treadmill apparatus. SCBF and SKBF were measured using a laser-Doppler flow meter. Drugs were administered orally twice a day for 11 days from day 3 post-surgery. Treatment with OP-1206 alpha-CD significantly improved walking dysfunction on days 5, 7 and 14, and improved SCBF on day 14 post-surgery. SKBF remained unaffected. Treatment with nifedipine, ticlopidine or cilostazol had no significant effects on any of the parameters measured in this model. These data suggest that the therapeutic effect of OP-1206 alpha-CD is primarily mediated by the improved local SCBF at the territory of spinal stenosis and not due to improvement of peripheral perfusion and/or antiplatelet activity.

Alprostadil↗

[Ozone therapy and viscosity of blood and plasma, distance of intermittent claudication and certain biochemical plasma components in patients with occlusive arteriosclerosis of the lower limbs].

Blood and plasma viscosity, total lipids, triglycerides, total cholesterol, free fatty acids, fibrinogen, lipid-gram, and hematocrit were determined in 53 patients with occlusive arteriosclerosis in the lower limbs prior to and after ozone therapy. At the same time the distance of the intermittent claudication was measured. A significant prolongation of the distance walked painlessly, reduction in blood and plasma viscosity as well as the decrease in total cholesterol after therapy with ozone correlated with a decrease of the blood viscosity.

Aged↗

Platelets' glycoproteins and their ligands in patients with intermittent claudication.

BACKGROUND: Platelet thrombi play critical role in pathogenesis of cardiovascular complications in atherosclerotic peripheral arterial disease (PAOD). The aim of this study was to evaluate the concentration of platelets GP IIb/IIIa, GP I b/IX and plasma levels of their ligands (fibrinogen and vWF) and their relation to other atherosclerotic risk factors in the patients with intermittent claudication secondary to PAOD. METHODS: Consecutive patients of the University Vascular Clinic were studied: 64 claudicants and 38 controls were enrolled. The concentration of platelets GPII b/IIIa and GP Ib/IX was estimated by ELISA method using monoclonal antibody against GPII b/IIIa (CD41a) and GPI b/IX (CD42a Immunotech). Plasma levels of vWF, fibrinogen, and platelets were measured by routine METHODS RESULTS: Plasma vWF (145+/-41%), fibrinogen (3.8+/-1 g/l) and platelet concentration of GP Ib/IX (121.1+/-23.39), GPIIb/IIIa (117.9 6 +/-32.7%), as well as plasma lipids and uric acid were statistically higher in claudicants than in controls (vWF: 103+/-42%, fibrinogen: 2.9+/-0.5 g/l, GP Ib/IX: 100+/-16.9%, GP IIb/IIIa: 100+/-29.4%). We have observed statistically higher concentration of GP IIb/IIIa and GP Ib/IX in smoking patients than in non-smoking patients with PAOD and significant correlation between the concentration of GP Ib/IX and GP IIb/IIIa and plasma fibrinogen in patients with PAOD and controls. CONCLUSIONS: Our results demonstrate higher platelet concentration of GP Ib/IX,GP IIb/IIIa and elevated plasma levels of ligands for platelets receptors-fibrinogen and vWF in patients with PAOD. This prothrombotic conditions may explain increased cardiovascular morbidity and mortality in this patient's group.

Adult↗

Episodic intermittent claudication associated with a Baker's cyst.

Baker first described synovial cysts in the leg in connection with diseases of the knee joint. Whilst the majority are asymptomatic, some present as a localised swelling behind the knee, and others either compress the popliteal vein or rupture and can be misdiagnosed as deep vein thrombosis; transmitted pulsation through the cyst can suggest the presence of a popliteal aneurysm. This paper documents a case of intermittent claudication of the lower limb secondary to compression of the popliteal artery by a Baker's cyst.

Constriction, Pathologic↗

Intermittent claudication of the hand after creation of an arteriovenous fistula in the forearm.

Eighty-five patients were followed up at least 1 year after creation of an arteriovenous fistula in the forearm. The anastomosis was side-to-side in 33 patients, end-to-side in 33 and end-to-end in 19. Trophic lesions were not observed. Intermittent claudication of the hand was more frequent in patients with a side-to-side arteriovenous fistula (42 percent) than in those with end-to-side (21 percent) or end-to-end fistulas (16 percent). Clinical and x-ray studies indicate that two different mechanisms are responsible for cramping pains: arterial steal phenomenon and venous hypertension. Their relative importance depends on multiple hemodynamic factors that may vary with time.

Adolescent↗

The comprehensiveness of Medline and Embase computer searches. Searches for controlled trials of homoeopathy, ascorbic acid for common cold and ginkgo biloba for cerebral insufficiency and intermittent claudication.

OBJECTIVE: To assess the comprehensiveness of Medline and Embase computer searches for controlled trials. DESIGN: Comparison of articles found after an exhaustive search of the literature with the yield of a Medline or Embase search. This was performed for controlled clinical trials on the efficacy of three interventions: homoeopathy, ascorbic acid for common cold, and ginkgo biloba for intermittent claudication and cerebral insufficiency. The number of controlled trials found by exhaustive search of the literature was 107, 61 and 45, respectively. RESULTS: For homoeopathy, ascorbic acid and ginkgo the proportion of all trials found by Medline was 17%, 36% and 31% respectively and for Embase 13%, 25% and 58% respectively. After checking of the references in the Medline articles 44%, 79% and 76% of all trials were identified. After checking of the references in the Embase articles 42%, 72% and 93% of all trials were identified. About 20% of the articles was not correctly indexed. Of the best trials 68%, 91% and 83% could be found with Medline and 55%, 82% and 92% of the best trials were identified through Embase. CONCLUSIONS: For the topics mentioned, Medline and Embase searches are sufficient to get an impression of the evidence from controlled trials, but only if references in the articles are followed for further evidence. If one wants to get a more complete picture, additional search strategies make sense. Of course, this picture may be different for other topics.

Abstracting and Indexing↗

[Philosophy of the treatment of intermittent claudication].

Everything points to the prime importance of good health habits and the prevention of risk factors. Long-term medication has only a limited and still questionable impact. Surgery will never be proposed straight off, but only if the claudication is persistent and troublesome in an active individual. Lumbar sympathectomy always provides a degree of improvement and entails a minimal risk. There is no secondary deterioration. Yet in cases of associated phlebites, it can aggravate trophic skin problems. Reconstructive surgery gives far better immediate results but at the price of increased risk and a secondary deterioration that makes difficult repeat operations necessary. It is thus necessary to be very careful in using surgery to deal with intermittent claudications.

Humans↗