Effect of Telmisartan on Renal Outcomes

A Randomized Trial

  1. Johannes F.E. Mann, MD;
  2. Roland E. Schmieder, MD;
  3. Leanne Dyal, MSc;
  4. Matthew J. McQueen, MD;
  5. Helmut Schumacher, MD;
  6. Janice Pogue, PhD;
  7. Xingyu Wang, PhD;
  8. Jeffrey L. Probstfield, MD;
  9. Alvaro Avezum, MD, PhD;
  10. Ernesto Cardona-Munoz, PhD;
  11. Gilles R. Dagenais, MD;
  12. Rafael Diaz, MD;
  13. George Fodor, MD, PhD;
  14. Jean M. Maillon, MD;
  15. Lars Rydén, MD;
  16. Cheuk M. Yu, MD;
  17. Koon K. Teo, MD;
  18. Salim Yusuf, DPh, MD; and
  19. for the TRANSCEND (Telmisartan Randomised Assessment Study in ACE Intolerant Subjects with Cardiovascular Disease) Investigators
  1. From Schwabing General Hospital and KfH Kidney Center, Ludwig Maximilians University, Munich, Germany; Friedrich Alexander University, Erlangen, Germany; Population Health Research Institute, McMaster University, Hamilton, Ontario, Canada; Boehringer Ingelheim, Ingelheim, Germany; Beijing Hypertension League Institute, Beijing, China; University of Washington, Seattle, Washington; Dante Pazzanese Institute of Cardiology, São Paulo, Brazil; University of Guadalajara, Guadalajara, Mexico; Institute of Cardiology and Pneumology, Laval University and Hospital, Quebec, Quebec, Canada; University of Buenos Aires, Buenos Aires, Argentina; Heart Institute, University of Ottawa, Ottawa, Ontario, Canada; University of Grenoble, Grenoble, France; Karolinska Institutet, Stockholm, Sweden; and Prince of Wales Hospital, Chinese University of Hong Kong, Hong Kong, China.

    Abstract

    Background: Angiotensin-receptor blockers (ARBs) blunt progression of advanced diabetic nephropathy, but their long-term renal effects in other patients are not clear.

    Objective: To examine the long-term renal effects of telmisartan versus placebo in adults at high vascular risk.

    Design: Randomized trial. Patients were randomly assigned by a central automated system between November 2001 and May 2004 and were followed until March 2008. Participants and investigators were blinded to intervention status.

    Setting: Multicenter, multinational study.

    Patients: 5927 adults with known cardiovascular disease or diabetes with end-organ damage but without macroalbuminuria or heart failure who cannot tolerate angiotensin-converting enzyme inhibitors.

    Intervention: Telmisartan, 80 mg/d (n = 2954), or matching placebo (n = 2972) plus standard treatment for a mean of 56 months.

    Measurements: Composite renal outcome of dialysis or doubling of serum creatinine, changes in estimated glomerular filtration rate (GFR), and changes in albuminuria.

    Results: No important difference was found in the composite renal outcome with telmisartan (58 patients [1.96%]) versus placebo (46 patients [1.55%]) (hazard ratio, 1.29 [95% CI, 0.87 to 1.89]; P = 0.20). Among the telmisartan and placebo groups, 7 and 10 patients had dialysis and 56 and 36 patients had doubling of serum creatinine, respectively (hazard ratio, 1.59 [CI, 1.04 to 2.41]; P = 0.031). Albuminuria increased less with telmisartan than with placebo (32% [CI, 23% to 41%] vs. 63% [CI, 52% to 76%]; P < 0.001). Decreases in estimated GFR were greater with telmisartan than with placebo (mean change in estimated GFR, −3.2 mL/min per 1.73 m2 [SD, 18.3] vs. −0.26 mL/min per 1.73 m2 [SD, 18.0]; P < 0.001).

    Limitation: Only 17 participants had dialysis.

    Conclusion: In adults with vascular disease but without macroalbuminuria, the effects of telmisartan on major renal outcomes were similar to those of placebo.

    Primary Funding Source: Boehringer Ingelheim.

    Article and Author Information

    • Grant Support: By Boehringer Ingelheim. Dr. Yusuf is supported by a Chair of the Heart and Stroke Foundation of Ontario.

    • Potential Financial Conflicts of Interest: Employment: H. Schumacher (Boehringer Ingelheim [manufacturer of telmisartan]). Consultancies: J.F.E. Mann (Boehringer Ingelheim), R.E. Schmieder (Boehringer Ingelheim), G.R. Dagenais (Boehringer Ingelheim, Sanofi-Aventis), S. Yusuf (Boehringer Ingelheim, AstraZeneca, Sanofi-Aventis, Servier, Bristol-Myers Squibb, GlaxoSmithKline). Honoraria: J.F.E. Mann (Boehringer Ingelheim), R.E. Schmieder (Boehringer Ingelheim, Sanofi-Aventis, AstraZeneca, Novartis, Roche), A. Avezum (Boehringer Ingelheim), G.R. Dagenais (Boehringer Ingelheim, Sanofi-Aventis), R. Diaz (Boehringer Ingelheim, Sanofi-Aventis), L. Rydén (Boehringer Ingelheim, Sanofi-Aventis, AstraZeneca), K.K. Teo (Boehringer Ingelheim), S. Yusuf (Boehringer Ingelheim, AstraZeneca, Sanofi-Aventis, Servier, Bristol-Myers Squibb, GlaxoSmithKline). Expert testimony: G.R. Dagenais (Sanofi-Aventis). Grants received: J.F.E. Mann (Boehringer Ingelheim), R.E. Schmieder (Boehringer Ingelheim, Novartis), J.L. Probstfield (Boehringer Ingelheim), G.R. Dagenais (Sanofi-Aventis), L. Rydén (Swedish Heart-Lung Foundation, AFA Insurance, Karolinska Institutet, Sanofi-Aventis), K.K. Teo (Boehringer Ingelheim), S. Yusuf (Boehringer Ingelheim, AstraZeneca, Sanofi-Aventis, Servier, Bristol-Myers Squibb, GlaxoSmithKline).

    • Reproducible Research Statement: Study protocol: Outlined elsewhere (8) and available from Dr. Teo (e-mail, teok{at}mcmaster.ca). Statistical code and data set: Not available.

    • Requests for Single Reprints: ONTARGET Office, McMaster University, Hamilton General Hospital, 237 Barton Street East, Hamilton, Ontario L8L 2X2, Canada; e-mail ontarget{at}phri.ca.

    • Current Author Addresses: Dr. Mann: Schwabing General Hospital, KfH Kidney Center, Ludwig Maximilians University, Kolner Platz 1, DE-80804 Munich, Germany.

    • Dr. Schmieder: Department of Nephrology and Hypertension, Friedrich Alexander University, DE-91054 Erlangen, Germany.

    • Ms. Dyal and Drs. Pogue, Teo, and Yusuf: Population Health Research Institute, McMaster University, 237 Barton Street East, Hamilton, Ontario L8L 2X2, Canada.

    • Dr. McQueen: Pathology and Molecular Medicine, McMaster University and Population Health Research Institute, 237 Barton Street East, Hamilton Ontario L8L 2X2, Canada.

    • Dr. Schumacher: Boehringer Ingelheim, DE-55091 Ingelheim, Germany.

    • Dr. Wang: Beijing Hypertension League Institute, Beijing, China.

    • Dr. Probstfield: Department of Medicine, University of Washington, Seattle, Washington.

    • Dr. Avezum: Dante Pazzanese Institute of Cardiology, São Paulo, Brazil.

    • Dr. Cardona-Munoz: Department of Physiology, University of Guadalajara, Guadalajara, Mexico.

    • Dr. Dagenais: Institute of Cardiology and Pneumology, Laval University and Hospital, Quebec, Quebec, Canada.

    • Dr. Diaz: Department of Medicine, University of Buenos Aires, Buenos Aires, Argentina.

    • Dr. Fodor: Heart Institute, University of Ottawa, Ottawa, Ontario, Canada.

    • Dr. Maillon: University of Grenoble, Grenoble, France.

    • Dr. Rydén: Cardiology Unit, Department of Medicine, Karolinska Institutet, Stockholm, Sweden.

    • Dr. Yu: Division of Cardiology, Prince of Wales Hospital, Chinese University of Hong Kong, Hong Kong, China.

    • Author Contributions: Conception and design: J.F.E. Mann, R.E. Schmieder, H. Schumacher, J. Pogue, E. Cardona-Munoz, L. Rydén, K.K. Teo, S. Yusuf.

    • Analysis and interpretation of the data: J.F.E. Mann, R.E. Schmieder, L. Dyal, J. Pogue, A. Avezum, E. Cardona-Munoz, G.R. Dagenais, L. Rydén, C.M. Yu, K.K. Teo, S. Yusuf.

    • Drafting of the article: J.F.E. Mann, E. Cardona-Munoz, L. Rydén, C.M. Yu.

    • Critical revision of the article for important intellectual content: J.F.E. Mann, R.E. Schmieder, M.J. McQueen, J.L. Probstfield, A. Avezum, E. Cardona-Munoz, G.R. Dagenais, G. Fodor, C.M. Yu, K.K. Teo, S. Yusuf.

    • Final approval of the article: J.F.E. Mann, R.E. Schmieder, J. Pogue, J.L. Probstfield, A. Avezum, E. Cardona-Munoz, G.R. Dagenais, R. Diaz, G. Fodor, J.M. Maillon, L. Rydén, C.M. Yu, K.K. Teo, S. Yusuf.

    • Provision of study materials or patients: M.J. McQueen, E. Cardona-Munoz, C.M. Yu.

    • Statistical expertise: L. Dyal, H. Schumacher, J. Pogue.

    • Obtaining of funding: J.F.E. Mann, S. Yusuf.

    • Administrative, technical, or logistic support: M.J. McQueen, J. Pogue, J.L. Probstfield, L. Rydén, K.K. Teo.

    • Collection and assembly of data: J.F.E. Mann, L. Dyal, J. Pogue, X. Wang, J.L. Probstfield, E. Cardona-Munoz, G.R. Dagenais, G. Fodor, C.M. Yu, S. Yusuf.

    • ClinicalTrials.gov registration number: NCT00153101.

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