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      Sulodexide improves pain-free walking distance in patients with lower extremity peripheral arterial disease: A systematic review and meta-analysis

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          Abstract

          Peripheral arterial disease is associated with very high cardiovascular risk. The main symptom is intermittent claudication, which strongly affects the quality of life. Therefore, treatment goals in peripheral arterial disease consist of the reduction of cardiovascular events and the relief of symptoms. An increase in pain-free walking distance, evaluated based on the Initial Claudication Distance, was also a strong positive prognostic factor in patients with peripheral arterial disease. Our objective was to reassess whether sulodexide is effective in improving Initial Claudication Distance. For this, we searched the literature according to the PRISMA checklist for double blind clinical trials assessing the improvement in the Initial Claudication Distance after 90 days of standard therapeutic regimen with sulodexide in adult patients with peripheral arterial disease. We found and assessed for bias in 11 studies eligible for review and meta-analysis. Data extracted from those studies favoured the sulodexide group, showing an overall difference in Initial Claudication Distance of +68.9 (CI 95%; ± 11.9 m) at the end of treatment (p < 0.001). According to this review, sulodexide is effective in improving Initial Claudication Distance and consequently the quality of life in patients with peripheral arterial disease. Further studies are needed to assess the effects of this drug on disease progression in asymptomatic patients with peripheral arterial disease.

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          Most cited references64

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          Rivaroxaban with or without aspirin in patients with stable peripheral or carotid artery disease: an international, randomised, double-blind, placebo-controlled trial

          Patients with peripheral artery disease have an increased risk of cardiovascular morbidity and mortality. Antiplatelet agents are widely used to reduce these complications.
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            Peripheral arterial disease in the elderly: The Rotterdam Study.

            To assess the age- and sex-specific prevalence of peripheral arterial disease (PAD) and intermittent claudication (IC) in an elderly population, we performed a population-based study in 7715 subjects (40% men, 60% women) aged 55 years and over. The presence of PAD and IC was determined by measuring the ankle-arm systolic blood pressure index (AAI) and by means of the World Health Organization/Rose questionnaire, respectively. PAD was considered present when the AAI was <0.90 in either leg. The prevalence of PAD was 19.1% (95% confidence interval, 18.1% to 20.0%): 16.9% in men and 20.5% in women. Symptoms of IC were reported by 1.6% (95% confidence interval, 1.3% to 1.9%) of the study population (2.2% in men, 1.2% in women). Of those with PAD, 6.3% reported symptoms of IC (8.7% in men, 4.9% in women), whereas in 68.9% of those with IC an AAI below 0.90 was found. Subjects with an AAI <0.90 were more likely to be smokers, to have hypertension, and to have symptomatic or asymptomatic cardiovascular disease compared with subjects with an AAI of 0.90 or higher. The authors conclude that the prevalence of PAD in the elderly is high whereas the prevalence of IC is rather low, although both prevalences clearly increase with advancing age. The vast majority of PAD patients reports no symptoms of IC.
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              Randomized trial of the effects of cholesterol-lowering with simvastatin on peripheral vascular and other major vascular outcomes in 20,536 people with peripheral arterial disease and other high-risk conditions.

              (2007)
              The Heart Protection Study (HPS) provides an opportunity to assess directly the effects of cholesterol-lowering therapy on major vascular events (defined as myocardial infarction, coronary death, stroke, or revascularization) in patients with peripheral arterial disease (PAD). In addition, the effects on peripheral vascular events (ie, non-coronary revascularization, aneurysm repairs, major amputations or PAD deaths) can be assessed. 6748 UK adults with PAD and 13,788 other high-risk participants were randomly allocated to receive 40 mg simvastatin daily or matching placebo, yielding an average LDL cholesterol difference of 1.0 mmol/L (39 mg/dL) during a mean of 5 years. For participants with PAD, allocation to simvastatin was associated with a highly significant 22% (95% CI 15-29) relative reduction in the rate of first major vascular event following randomisation (895 [26.4%] simvastatin-allocated vs 1101 [32.7%] placebo-allocated; P < .0001), which was similar to that seen among the other high-risk participants. The absolute reduction in first major vascular event was 63 (SE 11) per 1000 patients with PAD and 50 (SE 7) per 1000 without pre-existing PAD. Overall, among all participants, there was a 16% (5-25) relative reduction in the rate of first peripheral vascular event following randomisation (479 [4.7%] simvastatin vs 561 [5.5%] placebo), largely irrespective of baseline LDL cholesterol and other factors. This effect chiefly reflects a 20% (8-31) relative reduction in non-coronary revascularization procedures (334 [3.3%] vs 415 [4.0%]; P = .002). HPS demonstrates the benefits of cholesterol-lowering statin therapy in patients with PAD, regardless of their presenting cholesterol levels and other presenting features. Allocation to 40 mg simvastatin daily reduces the rate of first major vascular events by about one-quarter, and that of peripheral vascular events by about one-sixth, with large absolute benefits seen in participants with PAD because of their high vascular risk. Consequently, statin therapy should be considered routinely for all patients with PAD.
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                Author and article information

                Journal
                JRSM Cardiovasc Dis
                JRSM Cardiovasc Dis
                CVD
                spcvd
                JRSM Cardiovascular Disease
                SAGE Publications (Sage UK: London, England )
                2048-0040
                14 February 2020
                Jan-Dec 2020
                : 9
                : 2048004020907002
                Affiliations
                [1 ]EuroGenLab, Bologna, Italy
                [2 ]Department of Paediatrics, AUSL della Romagna, Ospedale Morgagni-Pierantoni, Forlì, Italy
                [3 ]Discipline of Cardiology, Clinical Emergency Hospital Bucharest, University of Medicine and Pharmacy “Carol Davila”, Bucharest, Romania
                [4 ]Department of Cardiology, ATS Sardegna, Italy
                [5 ]Discipline of Internal Medicine and Cardiology, University Emergency Hospital Bucharest, University of Medicine and Pharmacy “Carol Davila”, Bucharest, Romania
                Author notes
                [*]Oana Florentina Gheorghe-Fronea, Discipline of Cardiology, Clinical Emergency Hospital Bucharest, University of Medicine and Pharmacy “Carol Davila”, Calea Floreasca nr. 8, Sector 1, Bucharest, Romania. Email: dr.fronea79@ 123456gmail.com
                Author information
                https://orcid.org/0000-0002-1074-6979
                Article
                10.1177_2048004020907002
                10.1177/2048004020907002
                7025427
                060d23d9-486d-4deb-9b19-d0da63345d62
                © The Author(s) 2020

                Creative Commons Non Commercial CC BY-NC: This article is distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 License ( https://creativecommons.org/licenses/by-nc/4.0/) which permits non-commercial use, reproduction and distribution of the work without further permission provided the original work is attributed as specified on the SAGE and Open Access pages ( https://us.sagepub.com/en-us/nam/open-access-at-sage).

                History
                : 23 June 2019
                : 22 December 2019
                : 7 January 2020
                Funding
                Funded by: alfa sigma;
                Categories
                Review Article
                Custom metadata
                January-December 2020
                ts2

                peripheral arterial disease,lower extremity arterial disease,drug therapy,intermittent claudication,meta-analysis,walking distance

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