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Liffert Vogt - One of the best experts on this subject based on the ideXlab platform.
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blood pressure lowering effects of Sulodexide depend on albuminuria severity post hoc analysis of the Sulodexide microalbuminuria and macroalbuminuria studies
British Journal of Clinical Pharmacology, 2016Co-Authors: Rik H.g. Olde Engberink, Hiddo J.l. Heerspink, Dick De Zeeuw, Liffert VogtAbstract:Aims It has been suggested that Sulodexide is able to lower blood pressure (BP). This may be attributed to its ability to restore the endothelial surface layer (ESL). As ESL perturbation is known to be related to the degree of kidney damage, we investigated whether albuminuria, reflecting ESL status, modified the BP-lowering potential of Sulodexide. Methods A post hoc analysis of the double-blind, randomized, placebo-controlled Sulodexide microalbuminuria (Sun-MICRO) and macroalbuminuria (Sun-MACRO) studies, including 1056 microalbuminuric and 843 macroalbuminuric subjects with type 2 diabetes receiving maximal tolerated renin–angiotensin-aldosterone system inhibitor therapy, was carried out. We compared the effect of placebo and Sulodexide on systolic BP (SBP) among albuminuria groups. Results Analysis of covariance, including data from both trials, showed that baseline urine albumin-to-creatinine ratio (UACR) was the only modifier of the SBP response (interaction with treatment P = 0.001). In subjects with an UACR >1000 mg g–1, Sulodexide lowered SBP by 4.6 mmHg [95% confidence interval (CI) 3.6, 5.6; P < 0.001] compared with placebo, whereas a 2.3 mmHg (95% CI 0.9,3.7; P = 0.001) reduction was seen in subjects with a UACR of 300–1000 mg g–1. Sulodexide did not lower SBP in subjects with a UACR <300 mg g–1 (−0.2 mmHg, 95% CI −0.8, 0.5; P = 0.60). SBP-lowering effects were not accompanied by changes in body weight. Conclusion The BP-reducing potency of Sulodexide is modified by the degree of albuminuria in subjects with type 2 diabetes. As ESL status deteriorates with increasing albuminuria and nephropathy severity, this suggests that ESL restoration may represent a new target for BP treatment in subjects with diabetic nephropathy.
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Blood pressure-lowering effects of Sulodexide depend on albuminuria severity: post hoc analysis of the Sulodexide microalbuminuria and macroalbuminuria studies.
British Journal of Clinical Pharmacology, 2016Co-Authors: Rik H.g. Olde Engberink, Hiddo J.l. Heerspink, Dick De Zeeuw, Liffert VogtAbstract:Aims It has been suggested that Sulodexide is able to lower blood pressure (BP). This may be attributed to its ability to restore the endothelial surface layer (ESL). As ESL perturbation is known to be related to the degree of kidney damage, we investigated whether albuminuria, reflecting ESL status, modified the BP-lowering potential of Sulodexide. Methods A post hoc analysis of the double-blind, randomized, placebo-controlled Sulodexide microalbuminuria (Sun-MICRO) and macroalbuminuria (Sun-MACRO) studies, including 1056 microalbuminuric and 843 macroalbuminuric subjects with type 2 diabetes receiving maximal tolerated renin–angiotensin-aldosterone system inhibitor therapy, was carried out. We compared the effect of placebo and Sulodexide on systolic BP (SBP) among albuminuria groups. Results Analysis of covariance, including data from both trials, showed that baseline urine albumin-to-creatinine ratio (UACR) was the only modifier of the SBP response (interaction with treatment P = 0.001). In subjects with an UACR >1000 mg g–1, Sulodexide lowered SBP by 4.6 mmHg [95% confidence interval (CI) 3.6, 5.6; P
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The renoprotective effects of Sulodexide.
Drug design development and therapy, 2016Co-Authors: Rik H.g. Olde Engberink, Liffert VogtAbstract:Dear editor In their meta-analysis, Li et al1 reported a renoprotective benefit of Sulodexide in patients with diabetic nephropathy. This was the first meta-analysis to evaluate the potential anti-albuminuric effects of Sulodexide in such patients. Albuminuria reduction with renin–angiotensin–aldosterone system inhibitors is known to beneficially affect renal outcome and represents, together with blood pressure control, the cornerstone of diabetic nephropathy treatment.2–6 As (residual) albuminuria is closely related with renal outcome and the reduction in albuminuria is linearly correlated with renoprotection, we need additional measures to reduce the burden of diabetic nephropathy.7 The meta-analysis of Li et al1 therefore addresses a very relevant topic. In the light of two large randomized, placebo-controlled, double-blind clinical trials that did not show any effect of Sulodexide on albuminuria, the results of this meta-analysis are surprising, especially since the majority (86%) of patients that were included in this meta-analysis were derived from these trials.8,9 We want to address some crucial points that may underlie these remarkable results. First, in their continuous outcome analysis, Li et al1 excluded the trial of Lewis et al8 for unknown reasons. In our opinion, no valid conclusions can be drawn without taking into account this trial, which represented more than a third of the patients who were included in the meta-analysis. Second, the authors assigned arbitrary weights to the other studies that were included in this analysis. For example, the well-designed, multicenter trial of Packham et al that included 1,248 patients with a mean follow-up of 11 months was assigned a 13% weight,9 while a 21.5% weight was assigned to a single-center trial that included just 36 patients with a follow-up of 3 weeks.10 The authors used a random-effects model and determined weight using the inverse variance method. However, it is unclear how the ratio of mean values and accompanying confidence intervals were calculated. The results of the study by Packham et al that were incorporated in this meta-analysis (log ratio of values 0.99, 95% confidence interval 0.68–1.44) do not seem to correspond with the data that were reported in the original paper (log ratio of values 0.97, 95% confidence interval 0.91–1.03).9 We think the authors should address more thoroughly how these treatment effects were calculated and provide data of these calculations for each study. Both the addition of the trial by Lewis et al8 and adequate assignment of weights may have a significant impact on the outcome and conclusions of this analysis. In a second analysis, the authors assessed the treatment success of Sulodexide as a binary outcome. The results of this analysis may raise some concern. First, the authors incorrectly reported that 37 patients participated in the Sulodexide group of the study by Dedov et al,10 while only 18 patients were included. Second, it is unclear how the authors calculated the proportion of patients reaching this binary outcome. For instance, Dedov et al stated that “17 of the 18 Sulodexide-treated patients showed a trend toward a decrease in AER”.10 This is inconsistent with the proportion of 100% that reached the binary outcome according to Li et al.1 In general, such proportions cannot be extracted from the average albuminuria changes that are often reported in studies. The authors should therefore provide more insight and data of their calculations of this binary outcome. Third, out of three Sulodexide doses that were investigated by Gambaro et al,11 the authors chose to only include the highest and most effective dose. Lower Sulodexide doses were no predefined reason for exclusion. It remains unclear why these groups were not taken into account. Finally, the characteristics of the included studies were represented incorrectly in their baseline table (eg, the average amount of proteinuria was not 24.5 and 38.9 g/d in the studies of Dedov et al10 and Gambaro et al,11 respectively). Finally, in their discussion section, the authors came up with different mechanisms that may be responsible for the renoprotective effects of Sulodexide that were observed in their meta-analysis.1 Besides kidney-specific effects of Sulodexide, so far overlooked systemic blood pressure effects of Sulodexide have recently been reported.12 Considering that blood pressure regulation is the basis for renoprotective therapy, Sulodexide-induced blood pressure effects are of influence. Indeed, these blood pressure effects were shown to correlate well with changes in albuminuria.12 Improved blood pressure control by Sulodexide may therefore contribute to the anti-albuminuric characteristics of this agent. Without entering the debate whether Sulodexide should be further investigated for a possible renoprotective effect, the authors should revise their analysis and adjust their conclusions accordingly.
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the blood pressure lowering potential of Sulodexide a systematic review and meta analysis
British Journal of Clinical Pharmacology, 2015Co-Authors: Rik H.g. Olde Engberink, Hiddo J.l. Heerspink, Dick De Zeeuw, Nienke M G Rorije, Bertjan H Van Den Born, Liffert VogtAbstract:AIMS Sulodexide is a highly purified mixture of glycosaminoglycans that has been studied for its anti-albuminuric potential. Considering the effects of glycosaminoglycans on endothelial function and sodium homeostasis, we hypothesized that Sulodexide may lower blood pressure (BP). In this meta-analysis, we therefore investigated the antihypertensive effects of Sulodexide treatment. METHODS We selected randomized controlled trials that investigated Sulodexide treatment of at least 4 weeks and measured BP at baseline and after treatment. Two reviewers independently extracted data on study design, risk of bias, population characteristics and outcome measures. In addition, we contacted authors and pharmaceutical companies to provide missing data. RESULTS Eight studies, totalling 3019 subjects (mean follow-up 4.4 months) were included. Mean age was 61 years and mean baseline BP was 135/75 mmHg. Compared with control treatment, Sulodexide resulted in a significant systolic (2.2 mmHg [95% CI 0.3, 4.1], P = 0.02) and diastolic BP reduction (1.7 mmHg [95% CI 0.6, 2.9], P = 0.004). Hypertensive patients displayed the largest systolic BP and diastolic BP reductions (10.2/5.4 mmHg, P <0.001). Higher baseline systolic and diastolic BP were significantly associated with larger systolic (r(2) = 0.83, P <0.001) and diastolic BP (r(2) = 0.41, P = 0.02) reductions after Sulodexide treatment. In addition, systolic (r(2) = 0.41, P = 0.03) and diastolic BP reductions (r(2) = 0.60, P = 0.005) were significantly associated with albuminuria reduction. CONCLUSION Our data suggest that Sulodexide treatment results in a significant BP reduction, especially in hypertensive subjects. This indicates that endothelial glycosaminoglycans might be an independent therapy target in cardiovascular disease. Future studies should further address the BP lowering potential of Sulodexide.
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The blood pressure lowering potential of Sulodexide - a systematic review and meta-analysis
British journal of clinical pharmacology, 2015Co-Authors: Rik H.g. Olde Engberink, Hiddo J.l. Heerspink, Dick De Zeeuw, Nienke M G Rorije, Bertjan H Van Den Born, Liffert VogtAbstract:AIMS Sulodexide is a highly purified mixture of glycosaminoglycans that has been studied for its anti-albuminuric potential. Considering the effects of glycosaminoglycans on endothelial function and sodium homeostasis, we hypothesized that Sulodexide may lower blood pressure (BP). In this meta-analysis, we therefore investigated the antihypertensive effects of Sulodexide treatment. METHODS We selected randomized controlled trials that investigated Sulodexide treatment of at least 4 weeks and measured BP at baseline and after treatment. Two reviewers independently extracted data on study design, risk of bias, population characteristics and outcome measures. In addition, we contacted authors and pharmaceutical companies to provide missing data. RESULTS Eight studies, totalling 3019 subjects (mean follow-up 4.4 months) were included. Mean age was 61 years and mean baseline BP was 135/75 mmHg. Compared with control treatment, Sulodexide resulted in a significant systolic (2.2 mmHg [95% CI 0.3, 4.1], P = 0.02) and diastolic BP reduction (1.7 mmHg [95% CI 0.6, 2.9], P = 0.004). Hypertensive patients displayed the largest systolic BP and diastolic BP reductions (10.2/5.4 mmHg, P
Rik H.g. Olde Engberink - One of the best experts on this subject based on the ideXlab platform.
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blood pressure lowering effects of Sulodexide depend on albuminuria severity post hoc analysis of the Sulodexide microalbuminuria and macroalbuminuria studies
British Journal of Clinical Pharmacology, 2016Co-Authors: Rik H.g. Olde Engberink, Hiddo J.l. Heerspink, Dick De Zeeuw, Liffert VogtAbstract:Aims It has been suggested that Sulodexide is able to lower blood pressure (BP). This may be attributed to its ability to restore the endothelial surface layer (ESL). As ESL perturbation is known to be related to the degree of kidney damage, we investigated whether albuminuria, reflecting ESL status, modified the BP-lowering potential of Sulodexide. Methods A post hoc analysis of the double-blind, randomized, placebo-controlled Sulodexide microalbuminuria (Sun-MICRO) and macroalbuminuria (Sun-MACRO) studies, including 1056 microalbuminuric and 843 macroalbuminuric subjects with type 2 diabetes receiving maximal tolerated renin–angiotensin-aldosterone system inhibitor therapy, was carried out. We compared the effect of placebo and Sulodexide on systolic BP (SBP) among albuminuria groups. Results Analysis of covariance, including data from both trials, showed that baseline urine albumin-to-creatinine ratio (UACR) was the only modifier of the SBP response (interaction with treatment P = 0.001). In subjects with an UACR >1000 mg g–1, Sulodexide lowered SBP by 4.6 mmHg [95% confidence interval (CI) 3.6, 5.6; P < 0.001] compared with placebo, whereas a 2.3 mmHg (95% CI 0.9,3.7; P = 0.001) reduction was seen in subjects with a UACR of 300–1000 mg g–1. Sulodexide did not lower SBP in subjects with a UACR <300 mg g–1 (−0.2 mmHg, 95% CI −0.8, 0.5; P = 0.60). SBP-lowering effects were not accompanied by changes in body weight. Conclusion The BP-reducing potency of Sulodexide is modified by the degree of albuminuria in subjects with type 2 diabetes. As ESL status deteriorates with increasing albuminuria and nephropathy severity, this suggests that ESL restoration may represent a new target for BP treatment in subjects with diabetic nephropathy.
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Blood pressure-lowering effects of Sulodexide depend on albuminuria severity: post hoc analysis of the Sulodexide microalbuminuria and macroalbuminuria studies.
British Journal of Clinical Pharmacology, 2016Co-Authors: Rik H.g. Olde Engberink, Hiddo J.l. Heerspink, Dick De Zeeuw, Liffert VogtAbstract:Aims It has been suggested that Sulodexide is able to lower blood pressure (BP). This may be attributed to its ability to restore the endothelial surface layer (ESL). As ESL perturbation is known to be related to the degree of kidney damage, we investigated whether albuminuria, reflecting ESL status, modified the BP-lowering potential of Sulodexide. Methods A post hoc analysis of the double-blind, randomized, placebo-controlled Sulodexide microalbuminuria (Sun-MICRO) and macroalbuminuria (Sun-MACRO) studies, including 1056 microalbuminuric and 843 macroalbuminuric subjects with type 2 diabetes receiving maximal tolerated renin–angiotensin-aldosterone system inhibitor therapy, was carried out. We compared the effect of placebo and Sulodexide on systolic BP (SBP) among albuminuria groups. Results Analysis of covariance, including data from both trials, showed that baseline urine albumin-to-creatinine ratio (UACR) was the only modifier of the SBP response (interaction with treatment P = 0.001). In subjects with an UACR >1000 mg g–1, Sulodexide lowered SBP by 4.6 mmHg [95% confidence interval (CI) 3.6, 5.6; P
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The renoprotective effects of Sulodexide.
Drug design development and therapy, 2016Co-Authors: Rik H.g. Olde Engberink, Liffert VogtAbstract:Dear editor In their meta-analysis, Li et al1 reported a renoprotective benefit of Sulodexide in patients with diabetic nephropathy. This was the first meta-analysis to evaluate the potential anti-albuminuric effects of Sulodexide in such patients. Albuminuria reduction with renin–angiotensin–aldosterone system inhibitors is known to beneficially affect renal outcome and represents, together with blood pressure control, the cornerstone of diabetic nephropathy treatment.2–6 As (residual) albuminuria is closely related with renal outcome and the reduction in albuminuria is linearly correlated with renoprotection, we need additional measures to reduce the burden of diabetic nephropathy.7 The meta-analysis of Li et al1 therefore addresses a very relevant topic. In the light of two large randomized, placebo-controlled, double-blind clinical trials that did not show any effect of Sulodexide on albuminuria, the results of this meta-analysis are surprising, especially since the majority (86%) of patients that were included in this meta-analysis were derived from these trials.8,9 We want to address some crucial points that may underlie these remarkable results. First, in their continuous outcome analysis, Li et al1 excluded the trial of Lewis et al8 for unknown reasons. In our opinion, no valid conclusions can be drawn without taking into account this trial, which represented more than a third of the patients who were included in the meta-analysis. Second, the authors assigned arbitrary weights to the other studies that were included in this analysis. For example, the well-designed, multicenter trial of Packham et al that included 1,248 patients with a mean follow-up of 11 months was assigned a 13% weight,9 while a 21.5% weight was assigned to a single-center trial that included just 36 patients with a follow-up of 3 weeks.10 The authors used a random-effects model and determined weight using the inverse variance method. However, it is unclear how the ratio of mean values and accompanying confidence intervals were calculated. The results of the study by Packham et al that were incorporated in this meta-analysis (log ratio of values 0.99, 95% confidence interval 0.68–1.44) do not seem to correspond with the data that were reported in the original paper (log ratio of values 0.97, 95% confidence interval 0.91–1.03).9 We think the authors should address more thoroughly how these treatment effects were calculated and provide data of these calculations for each study. Both the addition of the trial by Lewis et al8 and adequate assignment of weights may have a significant impact on the outcome and conclusions of this analysis. In a second analysis, the authors assessed the treatment success of Sulodexide as a binary outcome. The results of this analysis may raise some concern. First, the authors incorrectly reported that 37 patients participated in the Sulodexide group of the study by Dedov et al,10 while only 18 patients were included. Second, it is unclear how the authors calculated the proportion of patients reaching this binary outcome. For instance, Dedov et al stated that “17 of the 18 Sulodexide-treated patients showed a trend toward a decrease in AER”.10 This is inconsistent with the proportion of 100% that reached the binary outcome according to Li et al.1 In general, such proportions cannot be extracted from the average albuminuria changes that are often reported in studies. The authors should therefore provide more insight and data of their calculations of this binary outcome. Third, out of three Sulodexide doses that were investigated by Gambaro et al,11 the authors chose to only include the highest and most effective dose. Lower Sulodexide doses were no predefined reason for exclusion. It remains unclear why these groups were not taken into account. Finally, the characteristics of the included studies were represented incorrectly in their baseline table (eg, the average amount of proteinuria was not 24.5 and 38.9 g/d in the studies of Dedov et al10 and Gambaro et al,11 respectively). Finally, in their discussion section, the authors came up with different mechanisms that may be responsible for the renoprotective effects of Sulodexide that were observed in their meta-analysis.1 Besides kidney-specific effects of Sulodexide, so far overlooked systemic blood pressure effects of Sulodexide have recently been reported.12 Considering that blood pressure regulation is the basis for renoprotective therapy, Sulodexide-induced blood pressure effects are of influence. Indeed, these blood pressure effects were shown to correlate well with changes in albuminuria.12 Improved blood pressure control by Sulodexide may therefore contribute to the anti-albuminuric characteristics of this agent. Without entering the debate whether Sulodexide should be further investigated for a possible renoprotective effect, the authors should revise their analysis and adjust their conclusions accordingly.
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the blood pressure lowering potential of Sulodexide a systematic review and meta analysis
British Journal of Clinical Pharmacology, 2015Co-Authors: Rik H.g. Olde Engberink, Hiddo J.l. Heerspink, Dick De Zeeuw, Nienke M G Rorije, Bertjan H Van Den Born, Liffert VogtAbstract:AIMS Sulodexide is a highly purified mixture of glycosaminoglycans that has been studied for its anti-albuminuric potential. Considering the effects of glycosaminoglycans on endothelial function and sodium homeostasis, we hypothesized that Sulodexide may lower blood pressure (BP). In this meta-analysis, we therefore investigated the antihypertensive effects of Sulodexide treatment. METHODS We selected randomized controlled trials that investigated Sulodexide treatment of at least 4 weeks and measured BP at baseline and after treatment. Two reviewers independently extracted data on study design, risk of bias, population characteristics and outcome measures. In addition, we contacted authors and pharmaceutical companies to provide missing data. RESULTS Eight studies, totalling 3019 subjects (mean follow-up 4.4 months) were included. Mean age was 61 years and mean baseline BP was 135/75 mmHg. Compared with control treatment, Sulodexide resulted in a significant systolic (2.2 mmHg [95% CI 0.3, 4.1], P = 0.02) and diastolic BP reduction (1.7 mmHg [95% CI 0.6, 2.9], P = 0.004). Hypertensive patients displayed the largest systolic BP and diastolic BP reductions (10.2/5.4 mmHg, P <0.001). Higher baseline systolic and diastolic BP were significantly associated with larger systolic (r(2) = 0.83, P <0.001) and diastolic BP (r(2) = 0.41, P = 0.02) reductions after Sulodexide treatment. In addition, systolic (r(2) = 0.41, P = 0.03) and diastolic BP reductions (r(2) = 0.60, P = 0.005) were significantly associated with albuminuria reduction. CONCLUSION Our data suggest that Sulodexide treatment results in a significant BP reduction, especially in hypertensive subjects. This indicates that endothelial glycosaminoglycans might be an independent therapy target in cardiovascular disease. Future studies should further address the BP lowering potential of Sulodexide.
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The blood pressure lowering potential of Sulodexide - a systematic review and meta-analysis
British journal of clinical pharmacology, 2015Co-Authors: Rik H.g. Olde Engberink, Hiddo J.l. Heerspink, Dick De Zeeuw, Nienke M G Rorije, Bertjan H Van Den Born, Liffert VogtAbstract:AIMS Sulodexide is a highly purified mixture of glycosaminoglycans that has been studied for its anti-albuminuric potential. Considering the effects of glycosaminoglycans on endothelial function and sodium homeostasis, we hypothesized that Sulodexide may lower blood pressure (BP). In this meta-analysis, we therefore investigated the antihypertensive effects of Sulodexide treatment. METHODS We selected randomized controlled trials that investigated Sulodexide treatment of at least 4 weeks and measured BP at baseline and after treatment. Two reviewers independently extracted data on study design, risk of bias, population characteristics and outcome measures. In addition, we contacted authors and pharmaceutical companies to provide missing data. RESULTS Eight studies, totalling 3019 subjects (mean follow-up 4.4 months) were included. Mean age was 61 years and mean baseline BP was 135/75 mmHg. Compared with control treatment, Sulodexide resulted in a significant systolic (2.2 mmHg [95% CI 0.3, 4.1], P = 0.02) and diastolic BP reduction (1.7 mmHg [95% CI 0.6, 2.9], P = 0.004). Hypertensive patients displayed the largest systolic BP and diastolic BP reductions (10.2/5.4 mmHg, P
Hiddo J.l. Heerspink - One of the best experts on this subject based on the ideXlab platform.
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blood pressure lowering effects of Sulodexide depend on albuminuria severity post hoc analysis of the Sulodexide microalbuminuria and macroalbuminuria studies
British Journal of Clinical Pharmacology, 2016Co-Authors: Rik H.g. Olde Engberink, Hiddo J.l. Heerspink, Dick De Zeeuw, Liffert VogtAbstract:Aims It has been suggested that Sulodexide is able to lower blood pressure (BP). This may be attributed to its ability to restore the endothelial surface layer (ESL). As ESL perturbation is known to be related to the degree of kidney damage, we investigated whether albuminuria, reflecting ESL status, modified the BP-lowering potential of Sulodexide. Methods A post hoc analysis of the double-blind, randomized, placebo-controlled Sulodexide microalbuminuria (Sun-MICRO) and macroalbuminuria (Sun-MACRO) studies, including 1056 microalbuminuric and 843 macroalbuminuric subjects with type 2 diabetes receiving maximal tolerated renin–angiotensin-aldosterone system inhibitor therapy, was carried out. We compared the effect of placebo and Sulodexide on systolic BP (SBP) among albuminuria groups. Results Analysis of covariance, including data from both trials, showed that baseline urine albumin-to-creatinine ratio (UACR) was the only modifier of the SBP response (interaction with treatment P = 0.001). In subjects with an UACR >1000 mg g–1, Sulodexide lowered SBP by 4.6 mmHg [95% confidence interval (CI) 3.6, 5.6; P < 0.001] compared with placebo, whereas a 2.3 mmHg (95% CI 0.9,3.7; P = 0.001) reduction was seen in subjects with a UACR of 300–1000 mg g–1. Sulodexide did not lower SBP in subjects with a UACR <300 mg g–1 (−0.2 mmHg, 95% CI −0.8, 0.5; P = 0.60). SBP-lowering effects were not accompanied by changes in body weight. Conclusion The BP-reducing potency of Sulodexide is modified by the degree of albuminuria in subjects with type 2 diabetes. As ESL status deteriorates with increasing albuminuria and nephropathy severity, this suggests that ESL restoration may represent a new target for BP treatment in subjects with diabetic nephropathy.
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Blood pressure-lowering effects of Sulodexide depend on albuminuria severity: post hoc analysis of the Sulodexide microalbuminuria and macroalbuminuria studies.
British Journal of Clinical Pharmacology, 2016Co-Authors: Rik H.g. Olde Engberink, Hiddo J.l. Heerspink, Dick De Zeeuw, Liffert VogtAbstract:Aims It has been suggested that Sulodexide is able to lower blood pressure (BP). This may be attributed to its ability to restore the endothelial surface layer (ESL). As ESL perturbation is known to be related to the degree of kidney damage, we investigated whether albuminuria, reflecting ESL status, modified the BP-lowering potential of Sulodexide. Methods A post hoc analysis of the double-blind, randomized, placebo-controlled Sulodexide microalbuminuria (Sun-MICRO) and macroalbuminuria (Sun-MACRO) studies, including 1056 microalbuminuric and 843 macroalbuminuric subjects with type 2 diabetes receiving maximal tolerated renin–angiotensin-aldosterone system inhibitor therapy, was carried out. We compared the effect of placebo and Sulodexide on systolic BP (SBP) among albuminuria groups. Results Analysis of covariance, including data from both trials, showed that baseline urine albumin-to-creatinine ratio (UACR) was the only modifier of the SBP response (interaction with treatment P = 0.001). In subjects with an UACR >1000 mg g–1, Sulodexide lowered SBP by 4.6 mmHg [95% confidence interval (CI) 3.6, 5.6; P
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the blood pressure lowering potential of Sulodexide a systematic review and meta analysis
British Journal of Clinical Pharmacology, 2015Co-Authors: Rik H.g. Olde Engberink, Hiddo J.l. Heerspink, Dick De Zeeuw, Nienke M G Rorije, Bertjan H Van Den Born, Liffert VogtAbstract:AIMS Sulodexide is a highly purified mixture of glycosaminoglycans that has been studied for its anti-albuminuric potential. Considering the effects of glycosaminoglycans on endothelial function and sodium homeostasis, we hypothesized that Sulodexide may lower blood pressure (BP). In this meta-analysis, we therefore investigated the antihypertensive effects of Sulodexide treatment. METHODS We selected randomized controlled trials that investigated Sulodexide treatment of at least 4 weeks and measured BP at baseline and after treatment. Two reviewers independently extracted data on study design, risk of bias, population characteristics and outcome measures. In addition, we contacted authors and pharmaceutical companies to provide missing data. RESULTS Eight studies, totalling 3019 subjects (mean follow-up 4.4 months) were included. Mean age was 61 years and mean baseline BP was 135/75 mmHg. Compared with control treatment, Sulodexide resulted in a significant systolic (2.2 mmHg [95% CI 0.3, 4.1], P = 0.02) and diastolic BP reduction (1.7 mmHg [95% CI 0.6, 2.9], P = 0.004). Hypertensive patients displayed the largest systolic BP and diastolic BP reductions (10.2/5.4 mmHg, P <0.001). Higher baseline systolic and diastolic BP were significantly associated with larger systolic (r(2) = 0.83, P <0.001) and diastolic BP (r(2) = 0.41, P = 0.02) reductions after Sulodexide treatment. In addition, systolic (r(2) = 0.41, P = 0.03) and diastolic BP reductions (r(2) = 0.60, P = 0.005) were significantly associated with albuminuria reduction. CONCLUSION Our data suggest that Sulodexide treatment results in a significant BP reduction, especially in hypertensive subjects. This indicates that endothelial glycosaminoglycans might be an independent therapy target in cardiovascular disease. Future studies should further address the BP lowering potential of Sulodexide.
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The blood pressure lowering potential of Sulodexide - a systematic review and meta-analysis
British journal of clinical pharmacology, 2015Co-Authors: Rik H.g. Olde Engberink, Hiddo J.l. Heerspink, Dick De Zeeuw, Nienke M G Rorije, Bertjan H Van Den Born, Liffert VogtAbstract:AIMS Sulodexide is a highly purified mixture of glycosaminoglycans that has been studied for its anti-albuminuric potential. Considering the effects of glycosaminoglycans on endothelial function and sodium homeostasis, we hypothesized that Sulodexide may lower blood pressure (BP). In this meta-analysis, we therefore investigated the antihypertensive effects of Sulodexide treatment. METHODS We selected randomized controlled trials that investigated Sulodexide treatment of at least 4 weeks and measured BP at baseline and after treatment. Two reviewers independently extracted data on study design, risk of bias, population characteristics and outcome measures. In addition, we contacted authors and pharmaceutical companies to provide missing data. RESULTS Eight studies, totalling 3019 subjects (mean follow-up 4.4 months) were included. Mean age was 61 years and mean baseline BP was 135/75 mmHg. Compared with control treatment, Sulodexide resulted in a significant systolic (2.2 mmHg [95% CI 0.3, 4.1], P = 0.02) and diastolic BP reduction (1.7 mmHg [95% CI 0.6, 2.9], P = 0.004). Hypertensive patients displayed the largest systolic BP and diastolic BP reductions (10.2/5.4 mmHg, P
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Sulodexide Fails to Demonstrate Renoprotection in Overt Type 2 Diabetic Nephropathy
Journal of the American Society of Nephrology : JASN, 2011Co-Authors: David K Packham, Hiddo J.l. Heerspink, Anne T Reutens, Julia B Lewis, Itamar Raz, Richard D Rohde, Rory Wolfe, Tomas Berl, Sarah E Ivory, Thomas B. WiegmannAbstract: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.
Tae Sun Park - One of the best experts on this subject based on the ideXlab platform.
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Sulodexide prevents peripheral nerve damage in streptozotocin induced diabetic rats
European Journal of Pharmacology, 2012Co-Authors: Heung Yong Jin, Kyung Ae Lee, Sun Kyung Song, Wei Jing Liu, Ji Hae Choi, Chang Ho Song, Hong Sun Baek, Tae Sun ParkAbstract:We investigated whether Sulodexide has additional protective effects against peripheral nerve damage caused by microvascular dysfunction in a rat model of diabetes. Female Sprague-Dawley (SD) rats were divided into the following 4 groups (n=7-9/group): Normal, Normal+Sulodexide (Sulodexide 10mg/kg), diabetic group, and diabetic+Sulodexide (Sulodexide 10mg/kg). We assessed current perception threshold, skin blood flow, superoxide dismutase, and proteinuria in experimental rats after oral administration of Sulodexide for 20 weeks. We also performed morphometric analysis of sciatic nerves and intraepidermal nerve fibers of the foot. Superoxide dismutase activity in the blood and sciatic nerve were increased significantly after Sulodexide treatment in the diabetic group. Current perception threshold was reduced at 2000 Hz (633.3 ± 24.15 vs 741.2 ± 23.5 μA, P<0.05) and skin blood flow was improved (10.90 ± 0.67 vs 8.85 ± 0.49 TPU, P<0.05) in the diabetic+Sulodexide group compared with the diabetic group. The mean myelinated axon area was significantly larger (56.6 ± 2.2 vs 49.8 ± 2.7 μm(2), P<0.05) and the intraepidermal nerve fiber density was significantly less reduced (6.27 ± 0.24 vs 5.40 ± 0.25/mm, P<0.05) in the diabetic+Sulodexide group compared to the diabetic group. Our results demonstrate that Sulodexide exhibits protective effects against peripheral nerve damage in a rat experimental model of diabetes. Therefore, these findings suggest that Sulodexide is a potential new therapeutic agent for diabetic peripheral neuropathy.
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Sulodexide prevents peripheral nerve damage in streptozotocin induced diabetic rats.
European journal of pharmacology, 2011Co-Authors: Heung Yong Jin, Kyung Ae Lee, Sun Kyung Song, Wei Jing Liu, Ji Hae Choi, Chang Ho Song, Hong Sun Baek, Tae Sun ParkAbstract:We investigated whether Sulodexide has additional protective effects against peripheral nerve damage caused by microvascular dysfunction in a rat model of diabetes. Female Sprague-Dawley (SD) rats were divided into the following 4 groups (n=7-9/group): Normal, Normal+Sulodexide (Sulodexide 10mg/kg), diabetic group, and diabetic+Sulodexide (Sulodexide 10mg/kg). We assessed current perception threshold, skin blood flow, superoxide dismutase, and proteinuria in experimental rats after oral administration of Sulodexide for 20 weeks. We also performed morphometric analysis of sciatic nerves and intraepidermal nerve fibers of the foot. Superoxide dismutase activity in the blood and sciatic nerve were increased significantly after Sulodexide treatment in the diabetic group. Current perception threshold was reduced at 2000 Hz (633.3 ± 24.15 vs 741.2 ± 23.5 μA, P
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blood pressure lowering effects of Sulodexide depend on albuminuria severity post hoc analysis of the Sulodexide microalbuminuria and macroalbuminuria studies
British Journal of Clinical Pharmacology, 2016Co-Authors: Rik H.g. Olde Engberink, Hiddo J.l. Heerspink, Dick De Zeeuw, Liffert VogtAbstract:Aims It has been suggested that Sulodexide is able to lower blood pressure (BP). This may be attributed to its ability to restore the endothelial surface layer (ESL). As ESL perturbation is known to be related to the degree of kidney damage, we investigated whether albuminuria, reflecting ESL status, modified the BP-lowering potential of Sulodexide. Methods A post hoc analysis of the double-blind, randomized, placebo-controlled Sulodexide microalbuminuria (Sun-MICRO) and macroalbuminuria (Sun-MACRO) studies, including 1056 microalbuminuric and 843 macroalbuminuric subjects with type 2 diabetes receiving maximal tolerated renin–angiotensin-aldosterone system inhibitor therapy, was carried out. We compared the effect of placebo and Sulodexide on systolic BP (SBP) among albuminuria groups. Results Analysis of covariance, including data from both trials, showed that baseline urine albumin-to-creatinine ratio (UACR) was the only modifier of the SBP response (interaction with treatment P = 0.001). In subjects with an UACR >1000 mg g–1, Sulodexide lowered SBP by 4.6 mmHg [95% confidence interval (CI) 3.6, 5.6; P < 0.001] compared with placebo, whereas a 2.3 mmHg (95% CI 0.9,3.7; P = 0.001) reduction was seen in subjects with a UACR of 300–1000 mg g–1. Sulodexide did not lower SBP in subjects with a UACR <300 mg g–1 (−0.2 mmHg, 95% CI −0.8, 0.5; P = 0.60). SBP-lowering effects were not accompanied by changes in body weight. Conclusion The BP-reducing potency of Sulodexide is modified by the degree of albuminuria in subjects with type 2 diabetes. As ESL status deteriorates with increasing albuminuria and nephropathy severity, this suggests that ESL restoration may represent a new target for BP treatment in subjects with diabetic nephropathy.
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Blood pressure-lowering effects of Sulodexide depend on albuminuria severity: post hoc analysis of the Sulodexide microalbuminuria and macroalbuminuria studies.
British Journal of Clinical Pharmacology, 2016Co-Authors: Rik H.g. Olde Engberink, Hiddo J.l. Heerspink, Dick De Zeeuw, Liffert VogtAbstract:Aims It has been suggested that Sulodexide is able to lower blood pressure (BP). This may be attributed to its ability to restore the endothelial surface layer (ESL). As ESL perturbation is known to be related to the degree of kidney damage, we investigated whether albuminuria, reflecting ESL status, modified the BP-lowering potential of Sulodexide. Methods A post hoc analysis of the double-blind, randomized, placebo-controlled Sulodexide microalbuminuria (Sun-MICRO) and macroalbuminuria (Sun-MACRO) studies, including 1056 microalbuminuric and 843 macroalbuminuric subjects with type 2 diabetes receiving maximal tolerated renin–angiotensin-aldosterone system inhibitor therapy, was carried out. We compared the effect of placebo and Sulodexide on systolic BP (SBP) among albuminuria groups. Results Analysis of covariance, including data from both trials, showed that baseline urine albumin-to-creatinine ratio (UACR) was the only modifier of the SBP response (interaction with treatment P = 0.001). In subjects with an UACR >1000 mg g–1, Sulodexide lowered SBP by 4.6 mmHg [95% confidence interval (CI) 3.6, 5.6; P
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the blood pressure lowering potential of Sulodexide a systematic review and meta analysis
British Journal of Clinical Pharmacology, 2015Co-Authors: Rik H.g. Olde Engberink, Hiddo J.l. Heerspink, Dick De Zeeuw, Nienke M G Rorije, Bertjan H Van Den Born, Liffert VogtAbstract:AIMS Sulodexide is a highly purified mixture of glycosaminoglycans that has been studied for its anti-albuminuric potential. Considering the effects of glycosaminoglycans on endothelial function and sodium homeostasis, we hypothesized that Sulodexide may lower blood pressure (BP). In this meta-analysis, we therefore investigated the antihypertensive effects of Sulodexide treatment. METHODS We selected randomized controlled trials that investigated Sulodexide treatment of at least 4 weeks and measured BP at baseline and after treatment. Two reviewers independently extracted data on study design, risk of bias, population characteristics and outcome measures. In addition, we contacted authors and pharmaceutical companies to provide missing data. RESULTS Eight studies, totalling 3019 subjects (mean follow-up 4.4 months) were included. Mean age was 61 years and mean baseline BP was 135/75 mmHg. Compared with control treatment, Sulodexide resulted in a significant systolic (2.2 mmHg [95% CI 0.3, 4.1], P = 0.02) and diastolic BP reduction (1.7 mmHg [95% CI 0.6, 2.9], P = 0.004). Hypertensive patients displayed the largest systolic BP and diastolic BP reductions (10.2/5.4 mmHg, P <0.001). Higher baseline systolic and diastolic BP were significantly associated with larger systolic (r(2) = 0.83, P <0.001) and diastolic BP (r(2) = 0.41, P = 0.02) reductions after Sulodexide treatment. In addition, systolic (r(2) = 0.41, P = 0.03) and diastolic BP reductions (r(2) = 0.60, P = 0.005) were significantly associated with albuminuria reduction. CONCLUSION Our data suggest that Sulodexide treatment results in a significant BP reduction, especially in hypertensive subjects. This indicates that endothelial glycosaminoglycans might be an independent therapy target in cardiovascular disease. Future studies should further address the BP lowering potential of Sulodexide.
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The blood pressure lowering potential of Sulodexide - a systematic review and meta-analysis
British journal of clinical pharmacology, 2015Co-Authors: Rik H.g. Olde Engberink, Hiddo J.l. Heerspink, Dick De Zeeuw, Nienke M G Rorije, Bertjan H Van Den Born, Liffert VogtAbstract:AIMS Sulodexide is a highly purified mixture of glycosaminoglycans that has been studied for its anti-albuminuric potential. Considering the effects of glycosaminoglycans on endothelial function and sodium homeostasis, we hypothesized that Sulodexide may lower blood pressure (BP). In this meta-analysis, we therefore investigated the antihypertensive effects of Sulodexide treatment. METHODS We selected randomized controlled trials that investigated Sulodexide treatment of at least 4 weeks and measured BP at baseline and after treatment. Two reviewers independently extracted data on study design, risk of bias, population characteristics and outcome measures. In addition, we contacted authors and pharmaceutical companies to provide missing data. RESULTS Eight studies, totalling 3019 subjects (mean follow-up 4.4 months) were included. Mean age was 61 years and mean baseline BP was 135/75 mmHg. Compared with control treatment, Sulodexide resulted in a significant systolic (2.2 mmHg [95% CI 0.3, 4.1], P = 0.02) and diastolic BP reduction (1.7 mmHg [95% CI 0.6, 2.9], P = 0.004). Hypertensive patients displayed the largest systolic BP and diastolic BP reductions (10.2/5.4 mmHg, P
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Sulodexide for Kidney Protection in Type 2 Diabetes Patients With Microalbuminuria: A Randomized Controlled Trial
American journal of kidney diseases : the official journal of the National Kidney Foundation, 2011Co-Authors: Edmund J. Lewis, Hiddo J.l. Heerspink, Dick De Zeeuw, Tom Greene, Julia B Lewis, Richard D Rohde, Lawrence G Hunsicker, Tomas Berl, Marc A. Pohl, Robert C. AtkinsAbstract:Background Sulodexide, a heterogenous group of sulfated glycosaminoglycans, includes low-molecular-weight heparin (∼80% ± 8%), high-molecular-weight heparin (∼5% ± 3%), and dermatan (∼20% ± 8%), with a mean molecular weight of ∼9 kDa. The drug is absorbed orally and has no anticoagulant effect in the doses used. Small preliminary studies consistently showed Sulodexide to be associated with decreased albuminuria in patients with diabetes. Study Design We conducted a multicenter placebo-controlled double-blinded study to determine the effect of Sulodexide on urine albumin excretion in patients with type 2 diabetic nephropathy. Setting & Participants Patients with type 2 diabetes and urine albumin-creatinine ratios (ACRs) of 35-200 mg/g in men and 45-200 mg/g in women were enrolled. Serum creatinine level was Intervention The study drug was Sulodexide, 200 mg/d. Outcome & Measurements The primary end point was normoalbuminuria (ACR 25%) or 50% decrease in baseline ACR. Results In 1,056 randomly assigned patients with a mean baseline ACR of 107.8 ± 83.7 mg/g, comparing the Sulodexide versus placebo groups, the primary end point was achieved in 16.5% versus 18.4%; normoalbuminuria, in 7.9% versus 6.1%; and a 50% decrease in albuminuria, in 15.4% versus 17.6%. The relative probability of any given change in albuminuria was identical in both groups. Limitations We were unable to determine whether the administered Sulodexide was absorbed from the gastrointestinal tract. Conclusion Sulodexide failed to decrease urine albumin excretion in patients with type 2 diabetic nephropathy and microalbuminuria.
