Effects of dual blockade of the renin-angiotensin system on renal and cardiovascular outcomes in type 2 diabetes with overt nephropathy and hypertension in the ORIENT: A post-hoc analysis (ORIENT-Hypertension)

Enyu Imai, Masakazu Haneda, Tetsu Yamasaki, Fumiaki Kobayashi, Atsushi Harada, Sadayoshi Ito, Juliana C.N. Chan, Hirofumi Makino

Research output: Contribution to journalArticle

18 Citations (Scopus)

Abstract

Combination therapy with angiotensin II receptor blockers and angiotensin-converting enzyme inhibitors (ACEIs) requires further evaluation in patients with diabetic nephropathy and hypertension. In a post hoc analysis of the Olmesartan Reducing Incidence of Endstage renal disease in diabetic Nephropathy Trial with hypertension, we examined the effects of olmesartan on renal and cardiovascular outcomes in the presence or absence of an ACEI. Among 563 patients randomized to receive either olmesartan (n=280) or placebo (n=283), 73.5% (n=414) received a concomitant ACEI. Compared with placebo, olmesartan significantly reduced proteinuria in both the ACEI-treated and non-ACEI-treated groups. The respective changes in the urinary protein creatinine ratio in the olmesartan-treated and placebo-treated groups were -32.6% and +21.1% without an ACEI (P=0.001) and -17.0% and +2.2% with an ACEI (P=0.028). In the olmesartan group, 115 patients developed primary renal outcomes (41.1%) compared with 129 (45.6%) in the placebo group (hazard ratio (HR): 0.97, P=0.787). The respective HRs in the ACEI-treated and non-ACEI-treated groups were 1.02 (P=0.891) and 0.84 (P=0.450). 40 olmesartan-treated patients (14.3%) and 53 placebo-treated patients (18.7%) developed secondary cardiovascular outcomes (HR: 0.65, P=0.042). The respective HRs in the ACEI-treated and non-ACEI-treated groups were 0.69 (P=0.129) and 0.51 (P=0.129). Olmesartan was well tolerated. Dual blockade treatment caused more hyperkalemia than monotherapy. In patients with diabetic nephropathy and hypertension, olmesartan significantly reduced proteinuria, independent of ACEI treatment and cardiovascular outcome but failed to show additional renal benefit compared with ACEI treatment alone. The cardiovascular benefit of dual treatment requires further evaluation.

Original languageEnglish
Pages (from-to)1051-1059
Number of pages9
JournalHypertension Research
Volume36
Issue number12
DOIs
Publication statusPublished - Dec 2013

Keywords

  • ACE inhibitor
  • diabetic nephropathy
  • olmesartan

ASJC Scopus subject areas

  • Internal Medicine
  • Physiology
  • Cardiology and Cardiovascular Medicine

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