Impact of the Angiotensin II Receptor Antagonist, Losartan, on Myocardial Fibrosis in Patients with End-Stage Renal Disease: Assessment by Ultrasonic Integrated Backscatter and Biochemical Markers

Myocardial fibrosis commonly occurs in patients with end-stage renal disease (ESRD) and has proven to be an important predictor for cardiovascular events. In experimental settings, angiotensin II type 1 receptor (AT1-R) antagonists have been shown to have anti-fibrotic effects on the myocardium independent of their antihypertensive effects. In this study, to investigate whether the AT1-R antagonist losartan would have such anti-fibrotic effects in patients, we administered losartan or, for purpose of comparison, the angiotensin-converting enzyme enalapril or Ca2+-antagonist amlodipine to patients with ESRD. Thirty-nine ESRD patients with hypertension were randomly assigned to receive losartan (n=13), enalapril (n=13), or amlodipine (n=13). Ultrasonic integrated backscatter (IBS) and serological markers of collagen type I synthesis and degradation were used to assess the degree of myocardial fibrosis just before and after 6 months of treatment. There were no significant differences in antihypertensive effects among the three agents. In the enalapril- and amlodipine-treated groups, the mean calibrated IBS values increased significantly after 6 months of treatment (enalapril: -31.6 +/- 1.3 to -29.4 +/- 1.2 dB, p=0.011; amlodipine: -30.6 +/- 1.4 to -27.2 +/- 1.2 dB, p=0.012). However, the mean calibrated IBS values in the losartan-treated group did not increase after 6 months of treatment (-31.2 +/- 1.7 to -31.3 +/- 1.4 dB, p=0.88). The ratio of the serum concentration of procollagen type I carboxy-terminal peptide to the serum concentration of collagen type I pyridinoline cross-linked carboxy-terminal telopeptide was significantly reduced in the losartan-treated group (42.6 +/- 4.6 to 34.4 +/- 3.6, p=0.038). The present study indicates that losartan more effectively suppresses myocardial fibrosis in patients with ESRD than does enalapril or amlodipine despite a comparable antihypertensive effect among the three drugs.