title: Cardiovascular and renal outcomes with telmisartan, ramipril, or both in people at high renal risk: results from the ONTARGET and TRANSCEND studies.
abstract: BACKGROUND
  In the Ongoing Telmisartan Alone and in Combination With Ramipril Global End Point Trial (ONTARGET), dual therapy did not reduce cardiovascular or renal outcomes compared with either angiotensin-converting enzyme inhibitors or angiotensin receptor blockers alone. Previous controlled trials with angiotensin-converting enzyme inhibitors or angiotensin receptor blockers have demonstrated greater cardiovascular and renal benefit in people with renal risk. We hypothesized that dual therapy would be more effective than monotherapy in patients with low glomerular filtration rate and elevated albuminuria.
  
  
  RESULTS
  Post hoc analysis was performed of renal subgroups of dual therapy versus monotherapy for the ONTARGET study and angiotensin receptor blocker versus placebo for the Telmisartan Randomized Assessment Study in ACE Intolerant Subjects With Cardiovascular Disease (TRANSCEND). The studies featured hazard ratios by subgroups and Cox regression models with factors for treatment, subgroup, and interactions. The main cardiovascular outcome was the composite of cardiovascular death, myocardial infarction, stroke, or hospitalization for heart failure, and the main renal outcome was the composite of chronic dialysis or doubling of creatinine. In ONTARGET, there was no cardiovascular or renal benefit from dual over monotherapy in any subgroup, even with low glomerular filtration rate and/or elevated albuminuria. In TRANSCEND, in the comparison of angiotensin receptor blocker with placebo, there was a significant interaction for the main renal outcome (P = 0.01) in the direction of harm for patients with normoalbuminuria (0.37 versus 0.16 events per 100 patient-years; hazard ratio, 2.35; confidence interval, 1.33 to 4.15) but a trend to benefit with microalbuminuria (0.52 versus 0.89 events per 100 patient-years; hazard ratio, 0.60; confidence interval, 0.25 to 1.46) and macroalbuminuria (1.57 versus 2.60 events per 100 patient-years; hazard ratio, 0.71; confidence interval, 0.21 to 2.44).
  
  
  CONCLUSIONS
  This post hoc analysis does not support dual therapy over monotherapy in high-vascular risk patients with low glomerular filtration rate or albuminuria. This observation is a post hoc comparison and should be interpreted appropriately.
  
  
  BACKGROUND
  URL: http://clinicaltrials.gov Identifier: NCT00153101.
authors.affiliation: Division of Nephrology, Department of Medicine, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, Ontario, Canada. sheldon.tobe@sunnybrook.ca
authors.forename: Sheldon W
authors.initials: SW
authors.lastname: Tobe
authors.forename: Catherine M
authors.initials: CM
authors.lastname: Clase
authors.forename: Peggy
authors.initials: P
authors.lastname: Gao
authors.forename: Matthew
authors.initials: M
authors.lastname: McQueen
authors.forename: Anja
authors.initials: A
authors.lastname: Grosshennig
authors.forename: Xingyu
authors.initials: X
authors.lastname: Wang
authors.forename: Koon K
authors.initials: KK
authors.lastname: Teo
authors.forename: Salim
authors.initials: S
authors.lastname: Yusuf
authors.forename: Johannes F E
authors.initials: JF
authors.lastname: Mann
mesh_terms: D000368:Aged; D000419:Albuminuria / Q000188:drug therapy / Q000401:mortality; D057911:Angiotensin Receptor Antagonists / Q000009:adverse effects / Q000627:therapeutic use*; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D001562:Benzimidazoles / Q000009:adverse effects / Q000627:therapeutic use*; D001565:Benzoates / Q000009:adverse effects / Q000627:therapeutic use*; D003404:Creatinine / Q000097:blood / Q000652:urine; D004359:Drug Therapy, Combination; D005260:Female; D005919:Glomerular Filtration Rate / Q000187:drug effects; D006333:Heart Failure / Q000188:drug therapy* / Q000401:mortality; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D007676:Kidney Failure, Chronic / Q000188:drug therapy* / Q000401:mortality; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000188:drug therapy* / Q000401:mortality; D017257:Ramipril / Q000009:adverse effects / Q000627:therapeutic use*; D020521:Stroke / Q000188:drug therapy* / Q000401:mortality; D000077333:Telmisartan; D016896:Treatment Outcome
chemical_list: D057911:Angiotensin Receptor Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors; D001562:Benzimidazoles; D001565:Benzoates; D003404:Creatinine; D017257:Ramipril; D000077333:Telmisartan