title: Renal outcomes with telmisartan, ramipril, or both, in people at high vascular risk (the ONTARGET study): a multicentre, randomised, double-blind, controlled trial.
abstract: BACKGROUND
  Angiotensin receptor blockers (ARB) and angiotensin converting enzyme (ACE) inhibitors are known to reduce proteinuria. Their combination might be more effective than either treatment alone, but long-term data for comparative changes in renal function are not available. We investigated the renal effects of ramipril (an ACE inhibitor), telmisartan (an ARB), and their combination in patients aged 55 years or older with established atherosclerotic vascular disease or with diabetes with end-organ damage.
  
  
  METHODS
  The trial ran from 2001 to 2007. After a 3-week run-in period, 25 620 participants were randomly assigned to ramipril 10 mg a day (n=8576), telmisartan 80 mg a day (n=8542), or to a combination of both drugs (n=8502; median follow-up was 56 months), and renal function and proteinuria were measured. The primary renal outcome was a composite of dialysis, doubling of serum creatinine, and death. Analysis was by intention to treat. This study is registered with ClinicalTrials.gov, number NCT00153101.
  
  
  RESULTS
  784 patients permanently discontinued randomised therapy during the trial because of hypotensive symptoms (406 on combination therapy, 149 on ramipril, and 229 on telmisartan). The number of events for the composite primary outcome was similar for telmisartan (n=1147 [13.4%]) and ramipril (1150 [13.5%]; hazard ratio [HR] 1.00, 95% CI 0.92-1.09), but was increased with combination therapy (1233 [14.5%]; HR 1.09, 1.01-1.18, p=0.037). The secondary renal outcome, dialysis or doubling of serum creatinine, was similar with telmisartan (189 [2.21%]) and ramipril (174 [2.03%]; HR 1.09, 0.89-1.34) and more frequent with combination therapy (212 [2.49%]: HR 1.24, 1.01-1.51, p=0.038). Estimated glomerular filtration rate (eGFR) declined least with ramipril compared with telmisartan (-2.82 [SD 17.2] mL/min/1.73 m(2)vs -4.12 [17.4], p<0.0001) or combination therapy (-6.11 [17.9], p<0.0001). The increase in urinary albumin excretion was less with telmisartan (p=0.004) or with combination therapy (p=0.001) than with ramipril.
  
  
  CONCLUSIONS
  In people at high vascular risk, telmisartan's effects on major renal outcomes are similar to ramipril. Although combination therapy reduces proteinuria to a greater extent than monotherapy, overall it worsens major renal outcomes.
authors: Schwabing General Hospital, and KfH Kidney Centre, Ludwig Maximilians University Munchen, Germany.
authors: Johannes F E
authors: JF
authors: Mann
authors: Roland E
authors: RE
authors: Schmieder
authors: Matthew
authors: M
authors: McQueen
authors: Leanne
authors: L
authors: Dyal
authors: Helmut
authors: H
authors: Schumacher
authors: Janice
authors: J
authors: Pogue
authors: Xingyu
authors: X
authors: Wang
authors: Aldo
authors: A
authors: Maggioni
authors: Andrzej
authors: A
authors: Budaj
authors: Suphachai
authors: S
authors: Chaithiraphan
authors: Kenneth
authors: K
authors: Dickstein
authors: Matyas
authors: M
authors: Keltai
authors: Kaj
authors: K
authors: Metsärinne
authors: Ali
authors: A
authors: Oto
authors: Alexander
authors: A
authors: Parkhomenko
authors: Leopoldo S
authors: LS
authors: Piegas
authors: Tage L
authors: TL
authors: Svendsen
authors: Koon K
authors: KK
authors: Teo
authors: Salim
authors: S
authors: Yusuf
mesh_terms: D000368:Aged; D047228:Angiotensin II Type 1 Receptor Blockers / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D001562:Benzimidazoles / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D001565:Benzoates / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D002318:Cardiovascular Diseases / Q000150:complications / Q000188:drug therapy*; D003404:Creatinine / Q000097:blood / Q000652:urine; D003920:Diabetes Mellitus / Q000188:drug therapy*; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D005500:Follow-Up Studies; D005919:Glomerular Filtration Rate / Q000187:drug effects; D006801:Humans; D007668:Kidney / Q000187:drug effects*; D008875:Middle Aged; D011507:Proteinuria / Q000139:chemically induced* / Q000378:metabolism; D017257:Ramipril / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D000077333:Telmisartan
chemical_list: D047228:Angiotensin II Type 1 Receptor Blockers; D000806:Angiotensin-Converting Enzyme Inhibitors; D001562:Benzimidazoles; D001565:Benzoates; D003404:Creatinine; D017257:Ramipril; D000077333:Telmisartan