Effectiveness and Safety of Ramipril Alone Compared With Telmisartan Alone and in Combination With Ramipril in Patients at High Risk for Cardiovascular Events. Patients Intolerant to Ramipril Were Entered in TRANSCEND, Telmisartan Compared to Placebo.

Summary

The Ongoing Telmisartan Alone and in combination wiht Ramipril Global Endpoint trial (ONTARGET): The primary objectives are to determine if (a) telmisartan 80mg daily and ramipril 10mg daily combination therapy is more effective in reducing the composite endpoint of Cardiovascular Death (CV) death, Myocardial infarction (MI), stroke or hospitalization for Congestive Heart Failure (CHF) compared with ramipril 10mg alone; and (b) telmisartan 80mg daily is at least as effective as (i.e. not less effective than) ramipril 10mg daily, on this endpoint. Telmisartan Randomised Assessment Study in Angiotension converting Enzyme inhibitor intolerant subjects with Cardiovascular Disease. (TRANSCEND): The primary objective of the study is to determine if treatment with telmisartan 80mg daily is superior to placebo reducing the composite endpoint of Cardiovascular Death (CV), Myocardial Infarction ( MI)I, stroke or hospitalization for Congestive Heart Failure (CHF) in patients who are intolerant to Angiotension Converting Enzyme inhibitors.

Timeline

Start

2001-11

Primary completion

2008-06

Completion

—

Publications

• Lee SF, Ramasundarahettige C, Gerstein HC, McIntyre WF, Eikelboom J, O'Donnell MJ, Zhou Y, Bangdiwala SI, Thabane L. Comparison of total event analysis and first event analysis in relation to heterogeneity in cardiovascular trials. BMC Med Res Methodol. 2025 Jun 9;25(1):159. doi: 10.1186/s12874-025-02593-3.
• Natale P, Palmer SC, Navaneethan SD, Craig JC, Strippoli GF. Angiotensin-converting-enzyme inhibitors and angiotensin receptor blockers for preventing the progression of diabetic kidney disease. Cochrane Database Syst Rev. 2024 Apr 29;4(4):CD006257. doi: 10.1002/14651858.CD006257.pub2.
• Haring B, Schumacher H, Mancia G, Teo KK, Lonn EM, Mahfoud F, Schmieder R, Mann JFE, Sliwa K, Yusuf S, Bohm M. Triglyceride-glucose index, low-density lipoprotein levels, and cardiovascular outcomes in chronic stable cardiovascular disease: results from the ONTARGET and TRANSCEND trials. Eur J Prev Cardiol. 2024 Feb 15;31(3):311-319. doi: 10.1093/eurjpc/zwad340.
• Cooper TE, Teng C, Tunnicliffe DJ, Cashmore BA, Strippoli GF. Angiotensin-converting enzyme inhibitors and angiotensin receptor blockers for adults with early (stage 1 to 3) non-diabetic chronic kidney disease. Cochrane Database Syst Rev. 2023 Jul 19;7(7):CD007751. doi: 10.1002/14651858.CD007751.pub3.
• Bohm M, Schumacher H, Werner C, Teo KK, Lonn EM, Mahfoud F, Speer T, Mancia G, Redon J, Schmieder RE, Sliwa K, Marx N, Weber MA, Laufs U, Williams B, Yusuf S, Mann JFE. Association between exercise frequency with renal and cardiovascular outcomes in diabetic and non-diabetic individuals at high cardiovascular risk. Cardiovasc Diabetol. 2022 Jan 20;21(1):12. doi: 10.1186/s12933-021-01429-w.
• Bohm M, Schumacher H, Teo KK, Lonn EM, Lauder L, Mancia G, Redon J, Schmieder RE, Sliwa K, Marx N, Weber MA, Williams B, Yusuf S, Mann JFE, Mahfoud F. Cardiovascular outcomes in patients at high cardiovascular risk with previous myocardial infarction or stroke. J Hypertens. 2021 Aug 1;39(8):1602-1610. doi: 10.1097/HJH.0000000000002822.
• Bohm M, Schumacher H, Teo KK, Lonn EM, Mahfoud F, Emrich I, Mancia G, Redon J, Schmieder RE, Sliwa K, Lehrke M, Marx N, Weber MA, Williams B, Yusuf S, Mann JFE. Renal outcomes and blood pressure patterns in diabetic and nondiabetic individuals at high cardiovascular risk. J Hypertens. 2021 Apr 1;39(4):766-774. doi: 10.1097/HJH.0000000000002697.
• Mancia G, Schumacher H, Bohm M, Mann JFE, Redon J, Facchetti R, Schmieder RE, Lonn EM, Teo KK, Yusuf S. Visit-to-visit blood pressure variability and renal outcomes: results from ONTARGET and TRANSCEND trials. J Hypertens. 2020 Oct;38(10):2050-2058. doi: 10.1097/HJH.0000000000002567.
• Dehghan M, Mente A, Rangarajan S, Mohan V, Lear S, Swaminathan S, Wielgosz A, Seron P, Avezum A, Lopez-Jaramillo P, Turbide G, Chifamba J, AlHabib KF, Mohammadifard N, Szuba A, Khatib R, Altuntas Y, Liu X, Iqbal R, Rosengren A, Yusuf R, Smuts M, Yusufali A, Li N, Diaz R, Yusoff K, Kaur M, Soman B, Ismail N, Gupta R, Dans A, Sheridan P, Teo K, Anand SS, Yusuf S. Association of egg intake with blood lipids, cardiovascular disease, and mortality in 177,000 people in 50 countries. Am J Clin Nutr. 2020 Apr 1;111(4):795-803. doi: 10.1093/ajcn/nqz348.
• Bohm M, Schumacher H, Teo KK, Lonn EM, Mahfoud F, Mann JFE, Mancia G, Redon J, Schmieder RE, Marx N, Sliwa K, Weber MA, Williams B, Yusuf S. Cardiovascular outcomes and achieved blood pressure in patients with and without diabetes at high cardiovascular risk. Eur Heart J. 2019 Jul 1;40(25):2032-2043. doi: 10.1093/eurheartj/ehz149.
• Bohm M, Schumacher H, Teo KK, Lonn EM, Mahfoud F, Ukena C, Mann JFE, Mancia G, Redon J, Schmieder RE, Sliwa K, Marx N, Weber MA, Williams B, Yusuf S. Resting heart rate and cardiovascular outcomes in diabetic and non-diabetic individuals at high cardiovascular risk analysis from the ONTARGET/TRANSCEND trials. Eur Heart J. 2020 Jan 7;41(2):231-238. doi: 10.1093/eurheartj/ehy808.
• Bohm M, Schumacher H, Teo KK, Lonn EM, Mahfoud F, Mann JFE, Mancia G, Redon J, Schmieder RE, Sliwa K, Weber MA, Williams B, Yusuf S. Achieved blood pressure and cardiovascular outcomes in high-risk patients: results from ONTARGET and TRANSCEND trials. Lancet. 2017 Jun 3;389(10085):2226-2237. doi: 10.1016/S0140-6736(17)30754-7. Epub 2017 Apr 5.
• Dunkler D, Kohl M, Teo KK, Heinze G, Dehghan M, Clase CM, Gao P, Yusuf S, Mann JF, Oberbauer R. Dietary risk factors for incidence or progression of chronic kidney disease in individuals with type 2 diabetes in the European Union. Nephrol Dial Transplant. 2015 Aug;30 Suppl 4:iv76-85. doi: 10.1093/ndt/gfv086.
• Bohm M, Schumacher H, Leong D, Mancia G, Unger T, Schmieder R, Custodis F, Diener HC, Laufs U, Lonn E, Sliwa K, Teo K, Fagard R, Redon J, Sleight P, Anderson C, O'Donnell M, Yusuf S. Systolic blood pressure variation and mean heart rate is associated with cognitive dysfunction in patients with high cardiovascular risk. Hypertension. 2015 Mar;65(3):651-61. doi: 10.1161/HYPERTENSIONAHA.114.04568. Epub 2015 Jan 12.
• Verdecchia P, Reboldi G, Angeli F, Trimarco B, Mancia G, Pogue J, Gao P, Sleight P, Teo K, Yusuf S. Systolic and diastolic blood pressure changes in relation with myocardial infarction and stroke in patients with coronary artery disease. Hypertension. 2015 Jan;65(1):108-14. doi: 10.1161/HYPERTENSIONAHA.114.04310. Epub 2014 Oct 20.
• Lonn EM, Rambihar S, Gao P, Custodis FF, Sliwa K, Teo KK, Yusuf S, Bohm M. Heart rate is associated with increased risk of major cardiovascular events, cardiovascular and all-cause death in patients with stable chronic cardiovascular disease: an analysis of ONTARGET/TRANSCEND. Clin Res Cardiol. 2014 Feb;103(2):149-59. doi: 10.1007/s00392-013-0644-4. Epub 2013 Dec 20.
• Heerspink HJ, Gao P, de Zeeuw D, Clase C, Dagenais GR, Sleight P, Lonn E, Teo KT, Yusuf S, Mann JF. The effect of ramipril and telmisartan on serum potassium and its association with cardiovascular and renal events: results from the ONTARGET trial. Eur J Prev Cardiol. 2014 Mar;21(3):299-309. doi: 10.1177/2047487313510678. Epub 2013 Nov 4.
• Dunkler D, Dehghan M, Teo KK, Heinze G, Gao P, Kohl M, Clase CM, Mann JF, Yusuf S, Oberbauer R; ONTARGET Investigators. Diet and kidney disease in high-risk individuals with type 2 diabetes mellitus. JAMA Intern Med. 2013 Oct 14;173(18):1682-92. doi: 10.1001/jamainternmed.2013.9051.
• Bohm M, Schumacher H, Laufs U, Sleight P, Schmieder R, Unger T, Teo K, Yusuf S. Effects of nonpersistence with medication on outcomes in high-risk patients with cardiovascular disease. Am Heart J. 2013 Aug;166(2):306-314.e7. doi: 10.1016/j.ahj.2013.04.016. Epub 2013 Jun 24.
• Dehghan M, Mente A, Teo KK, Gao P, Sleight P, Dagenais G, Avezum A, Probstfield JL, Dans T, Yusuf S; Ongoing Telmisartan Alone and in Combination With Ramipril Global End Point Trial (ONTARGET)/Telmisartan Randomized Assessment Study in ACEI Intolerant Subjects With Cardiovascular Disease (TRANSCEND) Trial Investigators. Relationship between healthy diet and risk of cardiovascular disease among patients on drug therapies for secondary prevention: a prospective cohort study of 31 546 high-risk individuals from 40 countries. Circulation. 2012 Dec 4;126(23):2705-12. doi: 10.1161/CIRCULATIONAHA.112.103234.
• Barzilay JI, Gao P, Clase CM, Mente A, Mann JF, Sleight P, Yusuf S, Teo KK; OnTARGET/TRANSCEND Investigators. Albuminuria and rapid loss of GFR and risk of new hip and pelvic fractures. Clin J Am Soc Nephrol. 2013 Feb;8(2):233-40. doi: 10.2215/CJN.06640712. Epub 2012 Nov 26.
• Kappert K, Bohm M, Schmieder R, Schumacher H, Teo K, Yusuf S, Sleight P, Unger T; ONTARGET/TRANSCEND Investigators. Impact of sex on cardiovascular outcome in patients at high cardiovascular risk: analysis of the Telmisartan Randomized Assessment Study in ACE-Intolerant Subjects With Cardiovascular Disease (TRANSCEND) and the Ongoing Telmisartan Alone and in Combination With Ramipril Global End Point Trial (ONTARGET). Circulation. 2012 Aug 21;126(8):934-41. doi: 10.1161/CIRCULATIONAHA.111.086660. Epub 2012 Jul 24.
• Neumann I, Grassi B. [Critically appraised article]. Rev Med Chil. 2012 Jan;140(1):117-20. Epub 2012 Apr 12. Spanish.
• Verdecchia P, Dagenais G, Healey J, Gao P, Dans AL, Chazova I, Binbrek AS, Iacobellis G, Ferreira R, Holwerda N, Karatzas N, Keltai M, Mancia G, Sleight P, Teo K, Yusuf S; Ongoing Telmisartan Alone and in Combination With Ramipril Global Endpoint TrialTelmisartan Randomized AssessmeNt Study in ACE iNtolerant subjects with cardiovascular Disease Investigators. Blood pressure and other determinants of new-onset atrial fibrillation in patients at high cardiovascular risk in the Ongoing Telmisartan Alone and in Combination With Ramipril Global Endpoint Trial/Telmisartan Randomized AssessmeNt Study in ACE iNtolerant subjects with cardiovascular Disease studies. J Hypertens. 2012 May;30(5):1004-14. doi: 10.1097/HJH.0b013e3283522a51.
• Redon J, Mancia G, Sleight P, Schumacher H, Gao P, Pogue J, Fagard R, Verdecchia P, Weber M, Bohm M, Williams B, Yusoff K, Teo K, Yusuf S; ONTARGET Investigators. Safety and efficacy of low blood pressures among patients with diabetes: subgroup analyses from the ONTARGET (ONgoing Telmisartan Alone and in combination with Ramipril Global Endpoint Trial). J Am Coll Cardiol. 2012 Jan 3;59(1):74-83. doi: 10.1016/j.jacc.2011.09.040.
• Mancia G, Schumacher H, Redon J, Verdecchia P, Schmieder R, Jennings G, Yusoff K, Ryden L, Liu GL, Teo K, Sleight P, Yusuf S. Blood pressure targets recommended by guidelines and incidence of cardiovascular and renal events in the Ongoing Telmisartan Alone and in Combination With Ramipril Global Endpoint Trial (ONTARGET). Circulation. 2011 Oct 18;124(16):1727-36. doi: 10.1161/CIRCULATIONAHA.110.008870. Epub 2011 Sep 26.
• Barzilay JI, Gao P, Ryden L, Schumacher H, Probstfield J, Commerford P, Dans A, Ferreira R, Keltai M, Paolasso E, Yusuf S, Teo K; TRANSCEND Investigators. Effects of telmisartan on glucose levels in people at high risk for cardiovascular disease but free from diabetes: the TRANSCEND study. Diabetes Care. 2011 Sep;34(9):1902-7. doi: 10.2337/dc11-0545. Epub 2011 Jul 25.
• Tobe SW, Clase CM, Gao P, McQueen M, Grosshennig A, Wang X, Teo KK, Yusuf S, Mann JF; ONTARGET and TRANSCEND Investigators. Cardiovascular and renal outcomes with telmisartan, ramipril, or both in people at high renal risk: results from the ONTARGET and TRANSCEND studies. Circulation. 2011 Mar 15;123(10):1098-107. doi: 10.1161/CIRCULATIONAHA.110.964171. Epub 2011 Feb 28.
• Barzilay JI, Gao P, O'Donnell M, Mann JF, Anderson C, Fagard R, Probstfield J, Dagenais GR, Teo K, Yusuf S; ONTARGET and TRANSCEND Investigators. Albuminuria and decline in cognitive function: The ONTARGET/TRANSCEND studies. Arch Intern Med. 2011 Jan 24;171(2):142-50. doi: 10.1001/archinternmed.2010.502.
• Dans AL, Teo K, Gao P, Chen JH, Jae-Hyung K, Yusoff K, Chaithiraphan S, Zhu J, Lisheng L, Yusuf S; Ongoing Telmisartan Alone and in Combination with Ramipril Global Endpoint Trial Investigators. In a subgroup of high-risk Asians, telmisartan was non-inferior to ramipril and better tolerated in the prevention of cardiovascular events. PLoS One. 2010 Dec 21;5(12):e13694. doi: 10.1371/journal.pone.0013694.
• Anderson C, Teo K, Gao P, Arima H, Dans A, Unger T, Commerford P, Dyal L, Schumacher H, Pogue J, Paolasso E, Holwerda N, Chazova I, Binbrek A, Young J, Yusuf S; ONTARGET and TRANSCEND Investigators. Renin-angiotensin system blockade and cognitive function in patients at high risk of cardiovascular disease: analysis of data from the ONTARGET and TRANSCEND studies. Lancet Neurol. 2011 Jan;10(1):43-53. doi: 10.1016/S1474-4422(10)70250-7. Epub 2010 Oct 25.
• Bohm M, Baumhakel M, Teo K, Sleight P, Probstfield J, Gao P, Mann JF, Diaz R, Dagenais GR, Jennings GL, Liu L, Jansky P, Yusuf S; ONTARGET/TRANSCEND Erectile Dysfunction Substudy Investigators. Erectile dysfunction predicts cardiovascular events in high-risk patients receiving telmisartan, ramipril, or both: The ONgoing Telmisartan Alone and in combination with Ramipril Global Endpoint Trial/Telmisartan Randomized AssessmeNt Study in ACE iNtolerant subjects with cardiovascular Disease (ONTARGET/TRANSCEND) Trials. Circulation. 2010 Mar 30;121(12):1439-46. doi: 10.1161/CIRCULATIONAHA.109.864199. Epub 2010 Mar 15.
• Verdecchia P, Sleight P, Mancia G, Fagard R, Trimarco B, Schmieder RE, Kim JH, Jennings G, Jansky P, Chen JH, Liu L, Gao P, Probstfield J, Teo K, Yusuf S; ONTARGET/TRANSCEND Investigators. Effects of telmisartan, ramipril, and their combination on left ventricular hypertrophy in individuals at high vascular risk in the Ongoing Telmisartan Alone and in Combination With Ramipril Global End Point Trial and the Telmisartan Randomized Assessment Study in ACE Intolerant Subjects With Cardiovascular Disease. Circulation. 2009 Oct 6;120(14):1380-9. doi: 10.1161/CIRCULATIONAHA.109.865774. Epub 2009 Sep 21.
• Sleight P, Redon J, Verdecchia P, Mancia G, Gao P, Fagard R, Schumacher H, Weber M, Bohm M, Williams B, Pogue J, Koon T, Yusuf S; ONTARGET investigators. Prognostic value of blood pressure in patients with high vascular risk in the Ongoing Telmisartan Alone and in combination with Ramipril Global Endpoint Trial study. J Hypertens. 2009 Jul;27(7):1360-9. doi: 10.1097/HJH.0b013e32832d7370.
• Mann JF, Schmieder RE, Dyal L, McQueen MJ, Schumacher H, Pogue J, Wang X, Probstfield JL, Avezum A, Cardona-Munoz E, Dagenais GR, Diaz R, Fodor G, Maillon JM, Ryden L, Yu CM, Teo KK, Yusuf S; TRANSCEND (Telmisartan Randomised Assessment Study in ACE Intolerant Subjects with Cardiovascular Disease) Investigators. Effect of telmisartan on renal outcomes: a randomized trial. Ann Intern Med. 2009 Jul 7;151(1):1-10, W1-2. doi: 10.7326/0003-4819-151-1-200907070-00122. Epub 2009 May 18.
• Telmisartan Randomised AssessmeNt Study in ACE iNtolerant subjects with cardiovascular Disease (TRANSCEND) Investigators; Yusuf S, Teo K, Anderson C, Pogue J, Dyal L, Copland I, Schumacher H, Dagenais G, Sleight P. Effects of the angiotensin-receptor blocker telmisartan on cardiovascular events in high-risk patients intolerant to angiotensin-converting enzyme inhibitors: a randomised controlled trial. Lancet. 2008 Sep 27;372(9644):1174-83. doi: 10.1016/S0140-6736(08)61242-8. Epub 2008 Aug 29.
• Mann JF, Schmieder RE, McQueen M, Dyal L, Schumacher H, Pogue J, Wang X, Maggioni A, Budaj A, Chaithiraphan S, Dickstein K, Keltai M, Metsarinne K, Oto A, Parkhomenko A, Piegas LS, Svendsen TL, Teo KK, Yusuf S; ONTARGET investigators. Renal outcomes with telmisartan, ramipril, or both, in people at high vascular risk (the ONTARGET study): a multicentre, randomised, double-blind, controlled trial. Lancet. 2008 Aug 16;372(9638):547-53. doi: 10.1016/S0140-6736(08)61236-2.
• ONTARGET Investigators; Yusuf S, Teo KK, Pogue J, Dyal L, Copland I, Schumacher H, Dagenais G, Sleight P, Anderson C. Telmisartan, ramipril, or both in patients at high risk for vascular events. N Engl J Med. 2008 Apr 10;358(15):1547-59. doi: 10.1056/NEJMoa0801317. Epub 2008 Mar 31.
• Held C, Gerstein HC, Yusuf S, Zhao F, Hilbrich L, Anderson C, Sleight P, Teo K; ONTARGET/TRANSCEND Investigators. Glucose levels predict hospitalization for congestive heart failure in patients at high cardiovascular risk. Circulation. 2007 Mar 20;115(11):1371-5. doi: 10.1161/CIRCULATIONAHA.106.661405. Epub 2007 Mar 5.

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