{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,28]],"date-time":"2026-08-28T23:36:13Z","timestamp":1787960173958,"version":"build-2784847793"},"reference-count":39,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"10","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Circulation"],"published-print":{"date-parts":[[2011,3,15]]},"abstract":"<jats:sec>\n            <jats:title>Background\u2014<\/jats:title>\n            <jats:p>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.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Methods and Results\u2014<\/jats:title>\n            <jats:p>\n              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 (\n              <jats:italic>P<\/jats:italic>\n              =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).\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusions\u2014<\/jats:title>\n            <jats:p>This post hoc analysis does not support dual therapy over monotherapy in high\u2013vascular risk patients with low glomerular filtration rate or albuminuria. This observation is a post hoc comparison and should be interpreted appropriately.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Clinical Trial Registration\u2014<\/jats:title>\n            <jats:p>\n              URL:\n              <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"uri\" xlink:href=\"http:\/\/clinicaltrials.gov\">http:\/\/clinicaltrials.gov<\/jats:ext-link>\n              Identifier: NCT00153101.\n            <\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/circulationaha.110.964171","type":"journal-article","created":{"date-parts":[[2011,3,1]],"date-time":"2011-03-01T21:11:39Z","timestamp":1299013899000},"page":"1098-1107","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":126,"title":["Cardiovascular and Renal Outcomes With Telmisartan, Ramipril, or Both in People at High Renal Risk"],"prefix":"10.1161","volume":"123","author":[{"given":"Sheldon W.","family":"Tobe","sequence":"first","affiliation":[{"name":"From the Division of Nephrology, Department of Medicine, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, Ontario, Canada (S.W.T.); Departments of Medicine and Clinical Epidemiology and Biostatistics (C.M.C.), Population Health Research Institute (P.G., M.M., K.K.T., S.Y.), and Department of Pathology and Molecular Medicine (M.M.), McMaster University, Hamilton, Ontario, Canada; Schwabing General Hospital and KfH Kidney Center, Munich, and Department of Medicine, Friedrich..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Catherine M.","family":"Clase","sequence":"additional","affiliation":[{"name":"From the Division of Nephrology, Department of Medicine, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, Ontario, Canada (S.W.T.); Departments of Medicine and Clinical Epidemiology and Biostatistics (C.M.C.), Population Health Research Institute (P.G., M.M., K.K.T., S.Y.), and Department of Pathology and Molecular Medicine (M.M.), McMaster University, Hamilton, Ontario, Canada; Schwabing General Hospital and KfH Kidney Center, Munich, and Department of Medicine, Friedrich..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peggy","family":"Gao","sequence":"additional","affiliation":[{"name":"From the Division of Nephrology, Department of Medicine, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, Ontario, Canada (S.W.T.); Departments of Medicine and Clinical Epidemiology and Biostatistics (C.M.C.), Population Health Research Institute (P.G., M.M., K.K.T., S.Y.), and Department of Pathology and Molecular Medicine (M.M.), McMaster University, Hamilton, Ontario, Canada; Schwabing General Hospital and KfH Kidney Center, Munich, and Department of Medicine, Friedrich..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew","family":"McQueen","sequence":"additional","affiliation":[{"name":"From the Division of Nephrology, Department of Medicine, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, Ontario, Canada (S.W.T.); Departments of Medicine and Clinical Epidemiology and Biostatistics (C.M.C.), Population Health Research Institute (P.G., M.M., K.K.T., S.Y.), and Department of Pathology and Molecular Medicine (M.M.), McMaster University, Hamilton, Ontario, Canada; Schwabing General Hospital and KfH Kidney Center, Munich, and Department of Medicine, Friedrich..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anja","family":"Grosshennig","sequence":"additional","affiliation":[{"name":"From the Division of Nephrology, Department of Medicine, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, Ontario, Canada (S.W.T.); Departments of Medicine and Clinical Epidemiology and Biostatistics (C.M.C.), Population Health Research Institute (P.G., M.M., K.K.T., S.Y.), and Department of Pathology and Molecular Medicine (M.M.), McMaster University, Hamilton, Ontario, Canada; Schwabing General Hospital and KfH Kidney Center, Munich, and Department of Medicine, Friedrich..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xingyu","family":"Wang","sequence":"additional","affiliation":[{"name":"From the Division of Nephrology, Department of Medicine, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, Ontario, Canada (S.W.T.); Departments of Medicine and Clinical Epidemiology and Biostatistics (C.M.C.), Population Health Research Institute (P.G., M.M., K.K.T., S.Y.), and Department of Pathology and Molecular Medicine (M.M.), McMaster University, Hamilton, Ontario, Canada; Schwabing General Hospital and KfH Kidney Center, Munich, and Department of Medicine, Friedrich..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Koon K.","family":"Teo","sequence":"additional","affiliation":[{"name":"From the Division of Nephrology, Department of Medicine, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, Ontario, Canada (S.W.T.); Departments of Medicine and Clinical Epidemiology and Biostatistics (C.M.C.), Population Health Research Institute (P.G., M.M., K.K.T., S.Y.), and Department of Pathology and Molecular Medicine (M.M.), McMaster University, Hamilton, Ontario, Canada; Schwabing General Hospital and KfH Kidney Center, Munich, and Department of Medicine, Friedrich..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Salim","family":"Yusuf","sequence":"additional","affiliation":[{"name":"From the Division of Nephrology, Department of Medicine, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, Ontario, Canada (S.W.T.); Departments of Medicine and Clinical Epidemiology and Biostatistics (C.M.C.), Population Health Research Institute (P.G., M.M., K.K.T., S.Y.), and Department of Pathology and Molecular Medicine (M.M.), McMaster University, Hamilton, Ontario, Canada; Schwabing General Hospital and KfH Kidney Center, Munich, and Department of Medicine, Friedrich..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Johannes F.E.","family":"Mann","sequence":"additional","affiliation":[{"name":"From the Division of Nephrology, Department of Medicine, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, Ontario, Canada (S.W.T.); 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