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Cited by 236Chronic Kidney Disease and DiabetesBlood Pressure and Hypertension StudiesRenin-Angiotensin System Studies

Effects of olmesartan on renal and cardiovascular outcomes in type 2 diabetes with overt nephropathy: a multicentre, randomised, placebo-controlled study

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for the ORIENT study investigators, Imai, E., Chan, J. C. N., Ito, S., Yamasaki, T., Kobayashi, F., Haneda, M., Makino, H.·2011·Diabetologia
DOI 10.1007/s00125-011-2325-zPMC PMC3210358
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Abstract

AIMS/HYPOTHESIS: The renal and cardiovascular protective effects of angiotensin receptor blocker (ARB) remain controversial in type 2 diabetic patients treated with a contemporary regimen including an angiotensin converting enzyme inhibitor (ACEI). METHODS: We examined the effects of olmesartan, an ARB, on primary composite outcome of doubling of serum creatinine, endstage renal disease and death in type 2 diabetic patients with overt nephropathy. Secondary outcome included composite cardiovascular outcomes, changes in renal function and proteinuria. Randomisation and allocation to trial group were carried out by a central computer system. Participants, caregivers, the people carrying out examinations and people assessing the outcomes were blinded to group assignment. RESULTS: Five hundred and seventy-seven (377 Japanese, 200 Chinese) patients treated with antihypertensive therapy (73.5% [n = 424] received concomitant ACEI), were given either once-daily olmesartan (10-40 mg) (n = 288) or placebo (n = 289) over 3.2 ± 0.6 years (mean±SD). In the olmesartan group, 116 developed the primary outcome (41.1%) compared with 129 (45.4%) in the placebo group (HR 0.97, 95% CI 0.75, 1.24; p = 0.791). Olmesartan significantly decreased blood pressure, proteinuria and rate of change of reciprocal serum creatinine. Cardiovascular death was higher in the olmesartan group than the placebo group (ten vs three cases), whereas major adverse cardiovascular events (cardiovascular death plus non-fatal stroke and myocardial infarction) and all-cause death were similar between the two groups (major adverse cardiovascular events 18 vs 21 cases, all-cause deaths; 19 vs 20 cases). Hyperkalaemia was more frequent in the olmesartan group than the placebo group (9.2% vs 5.3%). CONCLUSIONS/INTERPRETATION: Olmesartan was well tolerated but did not improve renal outcome on top of ACEI. TRIAL REGISTRATION: ClinicalTrials.gov NCT00141453.

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  • Prior trials of dual renin-angiotensin system blockade have failed to show cardiovascular or kidney protection among patients with CKD and type 2 diabetes.

    “Prior trials of dual renin–angiotensin system blockade have failed to show cardiovascular or kidney protection among patients with CKD and type 2 diabetes”

    From Cardiovascular and kidney outcomes with finerenone in patients with type 2 diabetes and chronic kidney disease: the FIDELITY pooled analysis (2022) · cites this paper as [26]

    The Conclusion reports no further improvement in renal outcomes with olmesartan in patients with type 2 diabetes and overt nephropathy, most of whom also received an ACE inhibitor. But the Results report a nonsignificant cardiovascular effect in the primary analysis and a benefit in a post hoc adjusted analysis. The Discussion also describes prior combination-therapy trials as mixed, not uniformly unsuccessful. The blanket claim about cardiovascular and kidney protection therefore overstates the paper. (LLM, conf=0.88)

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  • Discontinuation of the trial regimen due to hyperkalemia in this trial was markedly lower than in trials of dual RAS blockade (4.8% with combination therapy with a direct renin inhibitor and an ACE inhibitor or ARB and 9.2% with dual ACE inhibitor and ARB therapy).

    “markedly lower than in trials of dual RAS blockade (4.8% with combination therapy with a direct renin inhibitor and an ACE inhibitor or ARB 20 and 9.2% with dual ACE inhibitor and ARB therapy 22 )”

    From Effect of finerenone on chronic kidney disease outcomes in type 2 diabetes (2020) · cites this paper as [22]

    The Discussion section, “Safety of olmesartan in patients treated with ACEI” (page unavailable), reports hyperkalaemia in 9.2% of the olmesartan group versus 5.3% of the placebo group. It separately says approximately 20% discontinued because of adverse events. It does not identify 9.2% as the rate of discontinuation due to hyperkalaemia or as a rate specifically among patients receiving both an ACE inhibitor and an ARB. (LLM, conf=0.85)

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  • Previous kidney-outcome trials involving patients with CKD and type 2 diabetes targeting dual RAS blockade have shown a lack of efficacy and increased risk, including increased incidences of acute kidney injury, hypotension, and hyperkalemia.

    “Previous kidney-outcome trials that involved patients with CKD and type 2 diabetes targeting dual RAS blockade have shown a lack of efficacy and increased risk (including increased incidences of acute kidney injury, hypotension, and hyperkalemia) [20][21][22]”

    From Effect of finerenone on chronic kidney disease outcomes in type 2 diabetes (2020) · cites this paper as [22]

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  • Hemodynamic effects were also seen in trials of dual RAS blockade that did not show efficacy, which implicates other mechanisms.

    “hemodynamic effects were also seen in trials of dual RAS blockade that did not show efficacy, [20][21][22] which implicates other mechanisms.”

    From Effect of finerenone on chronic kidney disease outcomes in type 2 diabetes (2020) · cites this paper as [22]

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Research works printed but not linked: 19

  1. [2]Lam TH Liu LJ Janus ED Lam KSL Hedley AJ Fibrinogen, other cardiovascular risk factors and diabetes mellitus in Hong Kong Chinese: a community with high prevalence of type 2 diabetes mellitus and impaired glucose tolerance Diabetic Med 2000 17 798 806 10.1046/j.1464-5491.2000.00384.x 11131105 · DOI
  2. [6]Lui SF Ho YW Chau KF Leung CB Choy BY Hong Kong Renal Registry 1995–1999 Hong Kong J Nephrol 1999 1 53 60 10.1016/S1561-5413(09)60020-X · DOI
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  4. [8]Bakris GL Williams M Dworkin L Preserving renal function in adults with hypertension and diabetes: a consensus approach. National Kidney Foundation Hypertension and Diabetes Executive Committees Working Group Am J Kidney Dis 2000 36 646 661 10.1053/ajkd.2000.16225 10977801 · DOI
  5. [10]Lewis EJ Hunsicker LG Clarke WR Renoprotective effect of the angiotensin-receptor antagonist irbesartan in patients with nephropathy due to type 2 diabetes N Engl J Med 2001 345 851 860 10.1056/NEJMoa011303 11565517 · DOI · Paper page
  6. [11]Chan JC Wat NM So WY Renin angiotensin aldosterone system blockade and renal disease in patients with type 2 diabetes. An Asian perspective from the RENAAL Study Diabetes Care 2004 27 874 879 10.2337/diacare.27.4.874 15047641 · DOI
  7. [12]Kurokawa K Chan JC Cooper ME Keane WF Shahinfar S Zhang Z Renin angiotensin aldosterone system blockade and renal disease in patients with type 2 diabetes: a subanalysis of Japanese patients from the RENAAL Study Clin Exp Nephrol 2006 10 193 200 10.1007/s10157-006-0427-6 17009077 · DOI
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  10. [16]Imai E Ito S Haneda M Chan JC Makino H Olmesartan Reducing Incidence of Endstage Renal Disease in Diabetic Nephropathy Trial (ORIENT): rationale and study design Hypertens Res 2006 29 703 709 10.1291/hypres.29.703 17249526 · DOI
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Authors
for the ORIENT study investigators, Imai, E., Chan, J. C. N., Ito, S., Yamasaki, T., Kobayashi, F., Haneda, M., & Makino, H.
Affiliations
  • Nagoya University (JP)
  • Chinese University of Hong Kong (HK)
  • Tohoku University (JP)
  • Daiichi-Sankyo (Japan) (JP)
  • Asahikawa Medical University (JP)
  • Okayama University (JP)
Corresponding author
  • Imai, E.
  • Chan, J. C. N.
ORCID
Venue
Diabetologia
Publisher
Springer Science and Business Media LLC
Published
2011-10-13
Volume
54
Issue
12
Pages
2978-2986
ISSN
  • 0012-186X (ISSN-L)
  • 1432-0428
DOI
10.1007/s00125-011-2325-z
PMC
PMC3210358
OpenAlex
W2047335781
Cited by
236
References
7
Citations by year
2026: 4 · 2025: 4 · 2024: 13 · 2023: 12 · 2022: 18 · 2021: 13 · 2020: 17 · 2019: 9 · 2018: 17 · 2017: 18 · 2016: 16 · 2015: 24 · 2014: 22 · 2013: 24 · 2012: 23
FWCI
17.38
Type
journal article
Language
en
Open access
Licence
cc-by-nc
Locations
  • Diabetologia (publishedVersion, cc-by-nc)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by-nc)
  • PubMed Central (publishedVersion, cc-by-nc)
  • PubMed (publishedVersion)
Funders
Daiichi Sankyo Europe
Topics
  • Health Sciences › Medicine › Nephrology › Chronic Kidney Disease and Diabetes
  • Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Blood Pressure and Hypertension Studies
  • Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Renin-Angiotensin System Studies
Keywords
olmesartan, type 2 diabetes, diabetic nephropathy, angiotensin receptor blockers, ACE inhibitors, renal protection, cardiovascular outcomes, proteinuria, hyperkalemia, end-stage renal disease, cardiovascular mortality, antihypertensive therapy
MeSH terms
Antihypertensive Agents, Cardiovascular Diseases, Creatinine, Diabetes Mellitus, Type 2, Diabetic Nephropathies, Drug Therapy, Combination, Female, Humans, Hyperkalemia, Hypertension, Imidazoles, Kidney Failure, Chronic, Male, Middle Aged, Proteinuria, Tetrazoles, Treatment Outcome, Stroke, Asian People, Angiotensin II Type 1 Receptor Blockers

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