IPO-V2: A prospective, multicenter, randomized, comparative clinical investigation of the effects of sulodexide in preventing cardiovascular accidents in the first year after acute myocardial infarction

Condorelli, M; Chiariello, Massimo; Dagianti, A; Penco, María; Volta, Sergio Dalla; Pengo, Vittorio; Schivazappa, L; Mattioli, Giorgio; Mattioli, Anna Vittoria; Brusoni, B; Trotta, E.; Bignamini, A

doi:10.1016/0735-1097(94)90498-7

Cited by 54 publications

(36 citation statements)

References 26 publications

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“…Finally, heparin-like GAGs may modulate the procoagulant properties of endothelial cells through the increase of HS at the endothelial membrane level [19]. That these GAG activities may have therapeutic relevance in cardiovascular disease is supported by the reduction in total mortality, reinfarction rate and mural thrombus formation observed in patients treated with sulodexide after acute myocardial infarction [41].…”

Section: Perspectivesmentioning

confidence: 75%

Glycosaminoglycan therapy for long-term diabetic complications?

1998

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Long-term complications are the most important cause of mortality of diabetic patiens in western countries and diabetic nephropathy has emerged as a major determinant of end-stage renal failure [1]. Moreover, patients with diabetes mellitus have a high probability of developing acute cardiovascular disease, in particular myocardial infarction and cerebrovascular stroke which are the cause of death in nearly 80 % of this population [2]. Although data from the Diabetes Control and Complications Trial establish that hyperglycaemia has a central role in diabetic complications, strict metabolic control can be difficult to achieve. The search for new and ancillary approaches to diabetic complications is therefore warranted and understanding the distal pathway of glucose toxicity assumes clinical and therapeutical significance. Thus, evidence has been provided [3,4] that the alterations of the glycosaminoglycan (GAG) structure and metabolism may be of major importance for the development of diabetic complications. The aim of this article is to stress the hypothesis that GAGs might play an important role in the pathogenesis of late diabetic complications and that their treatment may be useful in several of these complications. GAG structure and functionGAGs are highly glycosylated and sulphated glycoproteins, consisting of dimeric repeated units containing an uronic acid (iduronic or glucuronic acid) and an aminosugar (glucosamine or galattosamine) [5]. These molecules are widely distributed in the body and prominent in extracellular matrices [5].Three major classes of GAGs have been described: a predominant large chondroitin sulphate, a small dermatan sulphate and a polydisperse heparan sulphate (HS) [5]. GAGs are vital in maintaining the structural integrity of the tissue and studies have shown that basement membranes contain HS in the form of a proteoglycan unique to that tissue [5]. HS forms anionic sites in this matrix and are thought to restrict the passage of proteins through the basement membrane [5]. GAG metabolism and diabetes mellitusIn diabetic patients, the increased macromolecular permeability within the glomeruli that precedes the onset of established renal lesions and the increased vascular permeability to albumin seem to be related to structural alterations in the macromolecular pathway, i. e. the extracellular matrix, between the endothelial cells [4]. The nature of this alteration may be related to the loss of negatively charged molecules of extracellular matrix and of the endothelium, among which HS is highly represented. A number of reports indicate that HS metabolism is impaired in diabetes and this is responsible for the extracellular matrix negative charge loss [4]. HS is a strongly negatively charged molecule that is structurally similar to heparin but its base polymer has a lower degree of processing (sulphation, epimerization) (Fig. 1). The HS chain imparts a negative charge to the basement membrane and determines the molecular charge permselectivity of the glomerular basement membrane [4]. Th...

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Section: Perspectivesmentioning

confidence: 75%

Glycosaminoglycan therapy for long-term diabetic complications?

1998

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“…Furthermore, sulodexide has other pharmacological effects potentially useful in the diabetic patients, subject to a high probability of developing acute cardiovascular diseases: anti-thrombotic activity, decrease of oxidative stress, hypolipidemic effect, prevention of glucose toxicity, suppression of cellular inflammation and anti-atheromatous effects [6]. Several clinical studies demonstrated sulodexide efficacy in patients, diabetic and not diabetic, affected by vascular diseases associated with a thrombotic risk: peripheral occlusive arterial diseases [29,30], prevention of recurrent deep venous thrombosis [31,32], diabetic retinopathy [33], diabetic foot [34,35], cerebrovascular [36,37] and cardiovascular diseases [38,39] and management of chronic venous disease, including the more severe and complicated cases such as venous ulcers [40][41][42].…”

Section: Discussionmentioning

confidence: 99%

A Clinical Experience on Sulodexide in the Treatment of Patients with Diabetic Nephropathy

Dakhli¹,

Khedher²,

Zidi³

et al. 2017

J Nephrol Ther

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“…There has been no report of altered hemostasis concomitant with sulodexide use in these settings. [36][37][38] The chemical content of sulodexide is characteristic of heparin compounds, and the sulfate content, sulfate/carbonyl ratios, and in vitro antifactor Xa activity reported to the US Food and Drug Administration (FDA) for sulodexide are well within the required ranges. 39 However, differences between glycosaminoglycan formulations between the drug used in previous studies and that used in this study cannot be ruled out.…”

Section: Discussionmentioning

confidence: 99%

Sulodexide Fails to Demonstrate Renoprotection in Overt Type 2 Diabetic Nephropathy

Packham

Wolfe

Reutens

et al. 2012

Journal of the American Society of Nephrology

161

137

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Sulodexide, a mixture of naturally occurring glycosaminoglycan polysaccharide components, has been reported to reduce albuminuria in patients with diabetes, but it is unknown whether it is renoprotective. This study reports the results from the randomized, double-blind, placebo-controlled, sulodexide macroalbuminuria (Sun-MACRO) trial, which evaluated the renoprotective effects of sulodexide in patients with type 2 diabetes, renal impairment, and significant proteinuria (.900 mg/d) already receiving maximal therapy with angiotensin II receptor blockers. The primary end point was a composite of a doubling of baseline serum creatinine, development of ESRD, or serum creatinine $6.0 mg/dl. We planned to enroll 2240 patients over approximately 24 months but terminated the study after enrolling 1248 patients. After 1029 person-years of follow-up, we did not detect any significant differences between sulodexide and placebo; the primary composite end point occurred in 26 and 30 patients in the sulodexide and placebo groups, respectively. Side effect profiles were similar for both groups. In conclusion, these data do not suggest a renoprotective benefit of sulodexide in patients with type 2 diabetes, renal impairment, and macroalbuminuria.

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IPO-V2: A prospective, multicenter, randomized, comparative clinical investigation of the effects of sulodexide in preventing cardiovascular accidents in the first year after acute myocardial infarction

Abstract: The study provides evidence that long-term therapy with sulodexide started early after an episode of acute myocardial infarction is associated with reductions in total mortality, rate of reinfarction and mural thrombus formation.

Cited by 54 publications

References 26 publications

Glycosaminoglycan therapy for long-term diabetic complications?

Glycosaminoglycan therapy for long-term diabetic complications?

A Clinical Experience on Sulodexide in the Treatment of Patients with Diabetic Nephropathy

Sulodexide Fails to Demonstrate Renoprotection in Overt Type 2 Diabetic Nephropathy

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