Research output: Contribution to journal › Article › Academic › peer-review
Blood pressure-lowering effects of sulodexide depend on albuminuria severity: post hoc analysis of the sulodexide microalbuminuria and macroalbuminuria studies. / Olde Engberink, Rik H. G.; Heerspink, Hiddo J. L.; de Zeeuw, Dick et al.
In: British journal of clinical pharmacology, Vol. 82, No. 5, 2016, p. 1351-1357.Research output: Contribution to journal › Article › Academic › peer-review
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TY - JOUR
T1 - Blood pressure-lowering effects of sulodexide depend on albuminuria severity: post hoc analysis of the sulodexide microalbuminuria and macroalbuminuria studies
AU - Olde Engberink, Rik H. G.
AU - Heerspink, Hiddo J. L.
AU - de Zeeuw, Dick
AU - Vogt, Liffert
PY - 2016
Y1 - 2016
N2 - 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. 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. 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. 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
AB - 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. 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. 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. 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
U2 - 10.1111/bcp.13062
DO - 10.1111/bcp.13062
M3 - Article
C2 - 27412828
VL - 82
SP - 1351
EP - 1357
JO - British journal of clinical pharmacology
JF - British journal of clinical pharmacology
SN - 0306-5251
IS - 5
ER -
ID: 3282448