The Shiga Microalbuminuria Reduction Trial (SMART) showed the advantage of ARB over CCB beyond the blood pressure (BP)-lowering effect in reducing microalbuminuria. To further assess the impact of BP control or renin-angiotensin system inhibition on microalbuminuria, the SMART patients were re-analyzed. Hypertensive patients with type 2 diabetes and microalbuminuria were randomly assigned to valsartan or amlodipine treatment groups for 24 weeks. Target blood pressure was set at <130/80 mmHg. Changes in the urinary albumin creatinine ratio (ACR) from baseline were assessed in the valsartan monotherapy (VM) group (n=33), the amlodipine monotherapy (AM) group (n=36), the concomitant valsartan and angiotensin-converting enzyme inhibitor group (VA) (n=33), and the concomitant amlodipine and angiotensin-converting enzyme inhibitor (AA) group (n=38). At the end of the study, mean BP was not different among the four treatment groups. The changes in ACR from baseline to the end of the treatment period in VM, AM, VA, and AA were -36%, +30%, -26%, and +8%, respectively. The dissociation between the anti-albuminuric and antihypertensive effects of valsartan or amlodipine was observed in the respective monotherapy groups. In the AA group, however, a significant positive relationship was found between the changes in ACR and those in systolic BP. In conclusion, RAS inhibitors may be necessary in order for calcium channel blockers to have an effect on microalbuminuria. Therefore, RAS inhibitors are first-line drugs for hypertensive patients with type 2 diabetes and microalbuminuria.
Trial registration: ClinicalTrials.gov NCT00202618.