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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.

british journal of clinical pharmacology

Blood pressure‐lowering effects of sulodexide depend on albuminuria severity:  post hoc  analysis of the sulodexide microalbuminuria and macroalbuminuria studies