Journal Article

Renal outcomes with telmisartan, ramipril, or both, in people at high vascular risk (the ONTARGET study): a multicentre, randomised, double-blind, controlled trial

Chaithiraphan, Suphachai, Wang, Xingyu, Mann, Johannes FE, McQueen, Matthew, Dyal, Leanne, Maggioni, Aldo, Oto, Ali, Schumacher, Helmut, Teo, Koon K, Yusuf, Salim, Budaj, Andrzej, Keltai, Matyas, Schmieder, Roland E, Pogue, Janice, Piegas, Leopoldo S, Svendsen, Tage L, Dickstein, Kenneth, Metsärinne, Kaj, Parkhomenko, Alexander

2008

Overview

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. 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. 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. 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. Boehringer-Ingelheim.

• Publisher: Elsevier Ltd,Elsevier Limited
• Subject: ACE inhibitors / Aged / Angiotensin II Type 1 Receptor Blockers - administration & dosage / Angiotensin II Type 1 Receptor Blockers - adverse effects / Angiotensin II Type 1 Receptor Blockers - therapeutic use / Angiotensin-Converting Enzyme Inhibitors - administration & dosage / Angiotensin-Converting Enzyme Inhibitors - adverse effects / Angiotensin-Converting Enzyme Inhibitors - therapeutic use / Benzimidazoles - administration & dosage / Benzimidazoles - adverse effects / Benzimidazoles - therapeutic use / Benzoates - administration & dosage / Benzoates - adverse effects / Benzoates - therapeutic use / Cardiovascular Diseases - complications / Cardiovascular Diseases - drug therapy / Clinical trials / Creatinine - blood / Creatinine - urine / Diabetes Mellitus - drug therapy / Dialysis / Disease / Double-Blind Method / Drug Therapy, Combination / Drugs / Follow-Up Studies / Glomerular Filtration Rate - drug effects / Humans / Internal Medicine / Kidney - drug effects / Kidneys / Middle Aged / Proteinuria - chemically induced / Proteinuria - metabolism / Ramipril - administration & dosage / Ramipril - adverse effects / Ramipril - therapeutic use / Renal function / Risk / Studies / Urine / Vascular diseases