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N Engl J Med. 2008 Apr 10;358(15):1547-59. doi: 10.1056/NEJMoa0801317. Epub 2008 Mar 31.

Telmisartan, ramipril, or both in patients at high risk for vascular events.

Collaborators (969)

Yusuf S, Sleight P, Anderson C, Teo K, Copland I, Ramos B, Richardson L, Murphy J, Haehl M, Hilbrich L, Svaerd R, Martin K, Murwin D, Meinicke T, Schlosser A, Schmidt G, Creek R, Schumacher H, Distel M, Aubert B, Pogue J, Dyal L, Schmieder R, Unger T, Asmar R, Mancia G, Diaz R, Paolasso E, Piegas L, Avezum A, Dagenais G, Cardona Munoz E, Probstfield J, Weber M, Young J, Fagard R, Jansky P, Mallion J, Mann J, Böhm M, Eber B, Karatzas NB, Keltai M, Trimarco B, Verdecchia P, Maggioni A, Verheugt FW, Holwerda NJ, Ceremuzynski L, Budaj A, Ferreira R, Chazova I, Rydén L, Svendsen TL, Metsärinne K, Dickstein K, Fodor G, Commerford P, Redon J, Luescher TR, Oto A, Binbrek A, Parkhomenko A, Jennings G, Liu LS, Yu CM, Dans AL, Shah R, Kim JH, Chen JH, Chaithiraphan S, Cairns J, Wilhelmsen L, Chalmers J, Wittes J, Gent M, Hennekens CH, Dagenais G, Anderson N, Avezum A, Budaj A, Fodor G, Keltai M, Maggioni A, Mann J, Parkhomenko A, Yusoff K, Auger P, Bernstein V, Lonn E, Panju A, Anand I, Bigger JT, Linz P, Healey J, Held C, McGorrian C, Rokoss M, Villar J, Sleight P, Anderson C, Creek R, Dans A, Diaz R, Fagard R, Probstfield J, Svaerd R, Teo K, Unger T, Yusuf S, Teo K, Copland I, Ramos B, McDonald A, Pogue J, Dyal L, Afzal R, Zhao F, Yusuf S, Sleight P, Richardson L, Anderson C, Murphy J, Diaz R, Paolasso E, Ahuad Guerrero RA, Amuchastegui M, Baglivo HP, Bendersky M, Bono J, Bustos B, Caccavo A, Cartasegna LR, Castellanos CR, Cipullo MA, Crunger P, Cuneo CA, Focaccia M, Fuselli JJ, Hasbani E, Hominal MA, Humphreys J, Inserra F, Killinger CR, Kuschnir E, Majul CR, Manuale OD, Martinez G, Marzetti EM, Nordaby R, Orlandini AD, Pomposiello JC, Rodríguez GM, Salas J, Salomone OA, Sanchez RA, Serra C, Vico ML, Jennings GL, Amerena JV, Arnolda LF, Aroney GM, Aylward PE, Bladin CF, Bridgeman JC, Chambers BR, Corbett AJ, Crimmins DS, Cross DB, Davies L, Davis SM, Donnan GA, Eccleston DS, Frayne JH, Hendriks R, Herkes GK, Hill AT, Jeffery IM, Karrasch JA, Koshy G, Marwick TH, Owensby DA, Parsons MW, Rees DM, Russell A, Schwartz R, Singh B, Thompson PL, Waites JH, Walsh WF, Walters DL, Watts RW, Whelan AP, Böhm M, Eber BE, Bonelli JB, Dolliner P, Hohenecker JH, Steurer GS, Weihs WW, Fagard R, Bekaert I, Brohet C, Chaumont P, Cheron P, Crasset V, Degaute JP, Dendale P, Dujardin K, Elshot S, Hellemans S, Herssens M, Heyndrickx G, Laloux P, Lesseliers H, Noyens P, Quinonez M, Stammen F, Striekwold H, Thoeng J, Van Mieghem W, Vanhooren G, Vervoort G, Vrolix M, Wollaert B, Piegas L, Avezum A, Abrantes JA, Armaganijan D, Ayoub JC, Bodanese LC, Carvalho AC, Coutinho M, Esteves JP, Franco RJ, Jardim PC, Saraiva JF, Leães PE, Maia LN, Marin-Neto JA, Mion D Jr, Moreira JR Jr, Oigman W, Pedrosa RC, Pelloso EA, Plavnik FL, Polanczyk CA, Rabelo A Jr, Rassi S, Reis G, Ribeiro AB, Ribeiro JM, Rocha JC, Rossi PR, Santos RD, Tarastchuk JC, Villalón MN, Teo K, Dagenais G, Abramson B, Arnold M, Ashton T, Auger P, Bata I, Bayly K, Beauchef J, Bélanger A, Bernstein V, Bhargava R, Booth AW, Bose S, Boulianne M, Cameron M, Chan YK, Constance C, Costi P, Dion D, Douketis J, Fell D, Giannoccaro JP, Glanz A, Gosselin G, Gould D, Goulet S, Grondin F, Gupta M, Gyenes G, Heath JW, Heath VA, Hess A, Hiscock JG, Hoag G, Honos G, Imrie J, Kuritzky R, Lai C, Lalani A, Lamy A, LeBouthillier P, Lochnan H, Lonn E, Lubelsky B, Mackey A, Meunier M, Milot A, Mitchell LB, Nawaz S, Omichinski M, Panju A, Pilon C, Pilon D, Polasek P, Proulx G, Rebane T, Ricci AJ, Rupka DW, Sabbah E, Savard D, Sharma NK, Shu D, St Hilaire R, St Maurice F, Starra R, Sussex B, Szaky T, Talbot P, Tan KW, To TB, Tobe S, Tytus R, Vexler R, Whitsitt P, Woo V, Liu L, Bai X, Chen X, Feng J, Fu S, Ge Y, Gong L, He Z, Huang J, Jiang Y, Li L, Li QH, Liao Y, Lu Z, Lu F, Ma S, Niu F, Pan C, Qian F, Shi X, Sun N, Sun M, Sun G, Wang J, Wang S, Wang Y, Wu Z, Yan X, Yang X, Yang H, Ye X, Yuan S, Zhang T, Zhang C, Zhang F, Zhang S, Zhao D, Zheng B, Zhou HY, Zhou S, Zhu J, Janský P, Dedek V, Dvorák J, Holaj R, Kotous J, Pederzoliová E, Polák M, Povolný J, Smetana K, Spác J, Svendsen TL, Götzsche L, Juhl HF, Koelendorf K, Lund P, Pedersen F, Perdersen OL, Pindborg T, Rasmussen LH, Rasmussen SL, Thygesen K, Tuxen C, Metsärinne K, Antikainen R, Jääskivi M, Kantola I, Kastarinen M, Kohonen-Jalonen P, Koistinen A, Lehmus E, Nuuttila R, Tuominen ML, Ylihärsilä H, Mallion J, Abenhaim N, Allix J, Boucher L, Bourgoin M, Boye A, Breton N, Cadinot D, Campagne A, Churet J, Constantin C, De Sainte Lorette E, El Sawy A, Etchegarray G, Farhat S, Lacoin F, Latte T, Magnani C, Pineau-Valenciennes D, Pithon M, Quéguiner A, Sicard J, Sorbe G, Taminau D, Vilarem H, Vogel JY, HEbert HH, Genth-Zotz S, Hermanns N, Holzer C, Minnich J, Schimkus D, Boehm M, Mann J, Brado B, Claus G, Dietz U, Griebenow R, Haak T, Hahn K, Hampel R, Heitzer H, Holle G, Horacek T, Jordan J, Klein C, Kolloch R, Ludewig S, Motz W, Muenzel T, Nast HP, Nauck M, Nebelsieck H, Rybak K, Samer H, Schaefer T, Scholze J, Schulze B, Schleppinghoff, Schmieder R, Schwaab B, Sechtem U, Sehnert W, Steinhagen-Thiessen E, Stenzel G, Trenkwalder P, Wedler B, Zippel J, Karatzas N, Achimastos A, Diamantopoulos E, Efstratopoulos A, Elisaf M, Karvounis H, Mentzikof D, Mytas D, Papadogiannis D, Pyrgakis V, Stefanadis C, Symeonidis D, Tsoukas A, Vogiatzis I, Voyaki S, Zamboulis C, Yu CM, Chan CK, Lam L, Lau YK, Sanderson J, Wong J, Wu EB, Yue CS, Keltai M, Czuriga I, Edes I, Farsang CS, Kalina A, Karlócai K, Keltai K, Kozma M, László Z, Nagy V, Nagy A, Polák GY, Préda I, Rónaszéki A, Sereg M, Simon K, Sonkodi S, Szegedi J, Timár S, Tóth K, Vándorfi GY, Vértes A, Feely J, Maher VM, Stanton AV, Sullivan P, Trimarco B, Verdecchia P, Maggioni A, Rosei EA, Ambrosio GB, Bentivoglio M, Branzi A, Perin PC, Chiariello M, Cirrincione V, Ferrari R, Gattobigio R, Giovannini E, Giugliano D, Lacchè A, Lauro R, Lembo G, Marchetti G, Moretti L, Pancaldi L, Partemi L, Pede S, Pettinati G, Reboldi G, Ricci R, Rosiello G, Rozza F, Sardone MG, Scabbia EV, Selvetella G, Tavazzi L, Terrosu P, Venco A, Vetrano A, Volpe M, Zilio G, Ismail T, Shah RP, Singaraveloo M, Ahmad WA, Yusof Z, Yusoff K, Abidin IZ, Zambahari R, Cardona Munoz E, Alcocer Diaz L, Pascoe-Gonzalez S, Arriaga Nava R, De la Peña Topete G, Elizondo Sifuentes LA, Hernández García HR, Illescas-Diaz J, Macías Islas MA, Noriega Arellano JA, Olvera Ruiz R, Parra Carrillo JZ, Velasco Sánchez G, Vidrio Velásquez M, Verheugt FW, Holwerda NJ, Basart DC, Boermans AJ, Bosker HA, Bouter KP, Buiks CP, de Backer WA, de Graaf JJ, Deppenbroek JH, Eefting FD, Gunneweg FC, Michels HR, Poldermans D, Schrijver G, Sedney MI, Slagboom T, Smilde JG, Storms GE, Tjon RM, van Bergen PF, van Doesburg GJ, van Kempen LH, van Mierlo HF, Veerman A, Vermetten FA, Wester A, Bagg W, Benatar J, Coxon R, Doughty RN, Friedlander DH, Luke RA, Nairn PL, Ratnasabapathy Y, Richards AM, Singh GP, Stewart RA, Troughton RW, White HD, Williams M, Wong SP, Dickstein K, Bogale N, Lier JO, Otterstad JE, Rønnevik PK, Skeie S, Walle PO, Dans AL, Abola MT, Añonuevo JC, Jaro JM, Marañon DR, Mendoza VL, Morales DR, Pacheco EP, Reyes EB, Roxas AA, Sedurante MB, Ceremuzynski L, Budaj A, Binio Z, Bronisz M, Buszman P, Czerski T, Dalkowski M, Gessek J, Gieroba A, Janik K, Janion M, Kawka-Urbanek T, Klabisz R, Krauze-Wielicka M, Malinowski S, Miekus P, Mormul J, Ogorek M, Opolski G, Skura M, Szpajer M, Tendera M, Waszyrowski T, Wierzchowiecki M, Zalska B, Ferreira R, Capucho R, Correia C, Cunha L, Ferro JM, Gama Ribeiro V, Gil V, Marques da Silva P, Oliveira Carrageta M, Sebra Gomes R, Veloso Gomes M, Chazova I, Ageev F, Belenkov Y, Ivleva A, Karpov Y, Shestakova M, Shlyakhto E, Shustov A, Sidorenko B, Chang HM, Kwok B, Fodor G, Dukát A, Gonsorcík J, Hranai M, Lietava J, Pella D, Rybar R, Ruffini L, Commerford P, Bonnici F, Brown B, Dalby AJ, Gibson GJ, Herbst L, King J, Klug E, Middle M, Naidoo DP, Pretorius M, Podgorski G, Ranjith N, Silwa-Hahnle K, Theron H, Kim JH, Chae SC, Chung NS, Hong KP, Jeong MH, Kang HJ, Kim JJ, Kim MH, Seo HS, Shin EK, Redón J, Abellán J, Aranda P, Barrios V, Calvo C, De La Figuera M, De Teresa E, Durá R, Escobar F, Fernandez-Cruz F, Galve E, Garcia-Puig J, Gil-Extremera B, Gomis R, Gonzalez-Albarran O, González-Juanatey JR, Llacer A, López-Bescós L, Oliván J, Picó A, Pose A, Roca-Cusachs A, Ruilope LM, Rydén L, Alvång A, Boström PA, Dellborg M, Ericsson UB, Herlitz J, Juhlin T, Pedersen K, Sträng B, Sundqvist B, Tengmark BO, Ulvenstam G, Westerdahl B, Winberg L, Luescher TR, Baumgartner I, Dubach P, Gallino A, Moccetti T, Noll G, Nordmann A, Rickli H, Schläpfer H, Weber K, Chen JH, Chao TH, Chen CY, Cheng JJ, Chiou HC, Fu CC, Fu M, Lai WT, Li YH, Lien LM, Tsai CD, Wang JH, Yeh PS, Chaithiraphan S, Chantadansuwan T, Jirasirirojanakorn K, Krittayaphong R, Laothavorn P, Mahanonda N, Sitthisook S, Tanomsup S, Tansuphaswadikul S, Tatsanavivat P, Yamwong S, Oto A, Akin M, Caglar NT, Ergin A, Müderrisoglu H, Oguz A, Ongen Z, Sansoy V, Tetiker T, Uysal A, Parkhomenko A, Amosova E, Cherkasova O, Dykun Y, Dzyak G, Galystska A, Grishyna O, Jaremenko O, Kononenko L, Koval E, Kovalenko V, Netyazhenko V, Pertseva T, Prokhorov A, Radchenko G, Rudyk YU, Sirenko Y, Skarzhevsky A, Binbrek AS, Al Hajiri AA, Al Hatou E, Al-Sousi AA, Alomairi M, Wajib IM, Sleight P, Adgey AA, Andrews R, Ball SG, Barer DH, Barnett AH, Bridges AB, Bryson V, Cowie AS, De Belder AJ, Donnelly R, Francis CM, Furnace J, Glen SK, Gough N, Heagerty AM, Jackson PR, Jackson SH, Joyce E, McEneaney DJ, Moriarty AJ, Murdoch DL, O'Hare JP, Penny WJ, Reid CJ, Tilley J, Vora JP, Webster J, Williams B, Probstfield J, Weber M, Young J, Ahmed I, Anand IS, Anderson JL, Aponte Pagán JS, Barzilay J, Basile JN, Bass PF 3rd, Blumenthal SS, Bommer WJ, Brautigam DF, Brown CD, Brown N, Byrum JD, Carr AA, Chinn J, Chiu D, Cho NR, Ciocon JO, Colón-Ortíz PJ, Cruz JB, Dachman WD, Dolson GM, Dorfman SG, Drummond W, East C, Eelani F, Ellison HS, Felicetta JV, Fishbach MH, Force RW, Giddings SJ, Goldberg MC, Goldman S, Gomez Adrover R, Goss SL, Graham SP, Granger CB, Greenspan MM, Grimm RH, Habib GB, Hagen MR, Hart PD, Hartney TJ, Henriquez MA, Holland JJ, Hoogwerf BJ, Hossfeld M, Jacobson AK, Jelley MJ, Jones TV, Kaplan RA, Karalis DG, Katz LA, Kereiakes DJ, Khan M, Kipperman RM, Kozinn MJ, Kozlowski JG, Lader EW, Landau C, Landzberg JS, Laughrun D, Lewis SJ, Liang CS, Limacher MC, Linz PE, Lo TS, Lopez-Arostegui F, Maddox RR, Mahrer PR, Maurer MS, McGuire DK, Mercando AD, Mersey JH, Meyer M, Mooss AN, Narayan P, Oparil S, Padhiar DN, Phillips AL, Prisant M, Qureshi N, Raghuwanshi MP, Randall RR, Retta TM, Ringrose RE, Rizvi AA, Rizvi MD, Saklayen MG, Sastrasinh S, Savani IK, Schlau A, Schultz HS, Schweiger MJ, Smith RD, Sosa-Padilla M, Streja D, Stuver TP, Subich DC, Sulak FC, Swagler WA 3rd, Taitano M, Tavarez-Valle JA, Taylor EM, White WB, Wickemeyer WJ, Wiegmann TB, Zee PA, Zhao XQ.

Author information

  • 1Population Health Research Institute, McMaster University and Hamilton Health Sciences, Hamilton, ON, Canada. yusufs@mcmaster.ca

Abstract

BACKGROUND:

In patients who have vascular disease or high-risk diabetes without heart failure, angiotensin-converting-enzyme (ACE) inhibitors reduce mortality and morbidity from cardiovascular causes, but the role of angiotensin-receptor blockers (ARBs) in such patients is unknown. We compared the ACE inhibitor ramipril, the ARB telmisartan, and the combination of the two drugs in patients with vascular disease or high-risk diabetes.

METHODS:

After a 3-week, single-blind run-in period, patients underwent double-blind randomization, with 8576 assigned to receive 10 mg of ramipril per day, 8542 assigned to receive 80 mg of telmisartan per day, and 8502 assigned to receive both drugs (combination therapy). The primary composite outcome was death from cardiovascular causes, myocardial infarction, stroke, or hospitalization for heart failure.

RESULTS:

Mean blood pressure was lower in both the telmisartan group (a 0.9/0.6 mm Hg greater reduction) and the combination-therapy group (a 2.4/1.4 mm Hg greater reduction) than in the ramipril group. At a median follow-up of 56 months, the primary outcome had occurred in 1412 patients in the ramipril group (16.5%), as compared with 1423 patients in the telmisartan group (16.7%; relative risk, 1.01; 95% confidence interval [CI], 0.94 to 1.09). As compared with the ramipril group, the telmisartan group had lower rates of cough (1.1% vs. 4.2%, P<0.001) and angioedema (0.1% vs. 0.3%, P=0.01) and a higher rate of hypotensive symptoms (2.6% vs. 1.7%, P<0.001); the rate of syncope was the same in the two groups (0.2%). In the combination-therapy group, the primary outcome occurred in 1386 patients (16.3%; relative risk, 0.99; 95% CI, 0.92 to 1.07); as compared with the ramipril group, there was an increased risk of hypotensive symptoms (4.8% vs. 1.7%, P<0.001), syncope (0.3% vs. 0.2%, P=0.03), and renal dysfunction (13.5% vs. 10.2%, P<0.001).

CONCLUSIONS:

Telmisartan was equivalent to ramipril in patients with vascular disease or high-risk diabetes and was associated with less angioedema. The combination of the two drugs was associated with more adverse events without an increase in benefit. (ClinicalTrials.gov number, NCT00153101 [ClinicalTrials.gov].).

Copyright 2008 Massachusetts Medical Society.

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PMID:
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