Effects of Folic Acid Therapy on the New-Onset Proteinuria in Chinese Hypertensive Patients: A Post Hoc Analysis of the Renal Substudy of CSPPT (China Stroke Primary Prevention Trial).

UNLABELLED: We aimed to test the hypothesis that treatment with enalapril and folic acid is more effective in preventing new-onset proteinuria than enalapril alone among hypertensive patients. This is a post hoc analysis of the renal substudy of the CSPPT (China Stroke Primary Prevention Trial). A total of 13 071 eligible participants without proteinuria were randomized to receive a double-blind daily treatment of a single tablet containing 10-mg enalapril and 0.8-mg folic acid (n=6511) or 10-mg enalapril alone (n=6560). The primary outcome was new-onset proteinuria, defined as a urine dipstick reading of ≥1+ at the exit visit. Secondary outcomes included a composite of the primary outcome and all-cause death and the annual rate of estimated glomerular filtration rate decline. After a median 4.4 years of treatment, the primary event occurred in 213 (3.9%) and 188 (3.5%) participants, respectively, in the enalapril and the enalapril-folic acid group (odds ratio, 0.90; 95% confidence interval, 0.74-1.11). However, among participants with diabetes mellitus at baseline, folic acid therapy resulted in a significant reduction in the risk for the primary event (3.7% in the enalapril-folic acid group versus 7.4% in the enalapril group; odds ratio, 0.48; 95% confidence interval, 0.29-0.81) and the composite event (odds ratio, 0.62; 95% confidence interval, 0.42-0.92) and a 55% slower annual rate of estimated glomerular filtration rate decline (0.5% versus 1.1% per year; P=0.002). Among those without diabetes mellitus at baseline, there were no between-group differences in all the outcomes. In conclusion, enalapril-folic acid therapy, compared with enalapril alone, significantly reduced the development of proteinuria in diabetic patients with hypertension.

CLINICAL TRIAL REGISTRATION: URL: http://www.ClinicalTrials.gov. Unique identifier: NCT00794885.