Vascular legacy beyond blood pressure control: benefits of perindopril/indapamide combination in hypertensive patients with diabetes

Objectives: Much of the chronic care of patients with type 2 diabetes mellitus and hypertension involves the prevention of diabetic complications. Renin-angiotensin system inhibitors are recommended as first-line therapies because of their nephroprotective properties. Their combination with metabolically neutral diuretics is recommended to reduce blood pressure, morbidity and mortality. Our objective was to review the mechanisms by which the combination of the angiotensin-converting enzyme inhibitor, perindopril, and metabolically neutral thiazide-like diuretic, indapamide, targets the pathways involved in microvascular and macrovascular diabetic complications. Methods: For this narrative review, extensive literature searches were performed using PubMed/Medline. Articles published in English describing clinical trials and mechanism of action studies that were relevant to the treatment of patients with perindopril and/or indapamide were included. Results: Perindopril/indapamide treatment has been shown to reduce blood pressure and to have significant beneficial effects on arterial distensibility, kidney structure and function, and endothelial function. Recent data also suggests that perindopril may reduce the deleterious accumulation of advanced glycation end products in diabetic tissue. In the Action in Diabetes and Vascular Disease: Preterax and Diamicron MR Controlled Evaluation diabetes trial, perindopril/indapamide treatment significantly reduced the relative risk of microvascular and macrovascular events by 9%, cardiovascular mortality by 18%, and all-cause mortality by 14%. Interestingly, 6 years after the end of the double-blind period, follow-up data showed that the beneficial effects on mortality continued to be significant even though differences in blood pressure and glycated hemoglobin levels had not been significant for several years. Together this data suggests that treatment with perindopril/indapamide has microvascular and macrovascular effects that extend beyond blood pressure lowering and that this treatment might confer a long-lasting beneficial vascular legacy. Conclusion: Moving forward, understanding the pathophysiological bases of the effects that extend beyond those of blood pressure control will help us differentiate between anti-hypertensive choices.