Efficacy of perindopril in reduction of cardiovascular events among patients with stable coronary artery disease: Randomised, double-blind, placebo-controlled, multicentre trial (the EUROPA study)

K. M. Fox, M. Bertrand, R. Ferrari, W. J. Remme, M. L. Simoons, M. Simoons, J. P. Bassand, J. Aldershvile, P. Hildebrandt, D. Cokkinos, P. Toutouzas, J. Eha, L. Erhardt, J. Erikssen, P. Grybauskas, U. Kalnins, K. Karsch, U. Sechtem, M. Keltai, W. KleinT. Lüscher, D. Mulcahy, M. Nieminen, A. Oto, O. Ozsaruhan, W. Paulus, L. Providencia, I. Riecansky, W. Ruzyllo, U. Santini, L. Tavazzi, J. Soler-Soler, P. Widimsky, D. Julian, H. Dargie, G. Murray, W. Kübler, K. Thygesen, D. Duprez, G. Steg, H. Drexel, G. Gombotz, D. Duprez, G. H. Heyndrickx, V. Legrand, P. Materne, W. Van Mieghem, P. Bocek, M. Branny, M. Cech, J. Charouzek, J. Drazka, L. Fabik, J. Florian, L. Francek, L. Groch, P. Havranek, J. Hradec, P. Jansky, R. Jirmar, I. Jokl, H. Krejcova, M. Kvasnak, T. Maratka, G. Marcinek, J. Moravcova, P. Nedbal, K. Peterka, J. Povolny, H. Rosolova, B. Semrad, K. Sochor, R. Spacek, J. Spinar, R. Stipal, K. Stuchlik, M. Sulda, J. Ulman, A. Vaclavicek, P. Vojtisek, H. Bjerregaard-Andersen, P. Hildebrandt, K. Kristensen, J. K. Madsen, J. Markenvard, J. Meibom, A. Norgaard, M. Scheibel, J. Eha, A. Leht, R. Teesalu, V. Vahula, A. Itkonen, J. Juvonen, J. Karmakoski, E. Kilkki, E. Koskela, J. Melin, M. S. Nieminen, R. Savola, T. Terho, L. M. Voipio-Pulkki, F. Apffel, P. Attali, C. Barjhoux, B. Baron, J. P. Bassand, Y. Berthier, P. Dambrine, E. Decoulx, P. Deshayes, R. Fouche, M. Genest, S. Godard, J. P. Guillot, G. Hanania, P. Khattar, F. Leroy, J. Mansourati, R. Piquemal, J. C. Quiret, P. Raynaud, D. Rondepierre, J. L. Roynard, S. Sudhibhasilp, E. Van Belle, A. Bilbal, B. Lauer, G. Rettig-Stürmer, R. Riessen, W. Rutsch, U. Sechtem, H. A. Sigel, R. Simon, C. Von Schacky, B. R. Winkelmann, C. Avgeropoulou, S. Christakos, S. Feggos, S. Floros, I. Fotiadis, I. Goudevenos, D. Kardara, C. Karidis, N. Koliopoulos, D. Kremastinos, I. Lekakis, A. Manolis, V. Pyrgakis, C. Papanikolaou, E. Papasteriadis, P. Skoufas, A. Stravrati, A. Stavridis, S. Syribeis, P. Vardas, I. Vassiliadis, V. Voudris, S. Zobolos, I. Berenyi, I. Edes, A. Janosi, E. Kalo, P. Karpati, S. Kornel, I. Pap, G. Polak, I. Reiber, M. Rusznak, J. Tarjan, S. Timar, K. Toth, J. Barton, P. Crean, K. Daly, P. Kearney, T. B. Meany, P. Quigley, R. Antolini, P. Azzolini, E. Bellone, A. Branzi, C. Brunelli, E. Capponi, A. Capucci, M. Casaccia, E. Cecchetti, V. Ceci, L. Celegon, A. Colombo, G. Corsini, F. Cucchini, S. Dalla Volta, R. De Caterina, I. De Luca, S. De Servi, M. Di Donato, U. Di Giacomo, G. Di Pasquale, C. Fiorentini, O. Gaddi, M. Giannetto, P. Giannuzzi, A. Giordano, E. Giovannini, M. Guarnierio, A. Iacono, G. Inama, R. Leghissa, R. Lorusso, G. Marinoni, M. Marzilli, F. Mauri, G. M. Mosele, S. Papi, G. Pela, G. Pettinati, M. R. Polimeni, F. Portaluppi, C. Proto, E. Renaldini, S. Riva, M. Sanguinetti, M. Santini, S. Severi, G. Sinagra, L. Tantalo, L. Tavazzi, S. F. Vajola, M. Volterrani, B. Ansmite, E. Gailiss, A. Gersamija, M. A. Ozolina, A. Baubiniene, E. Berukstis, L. Grigoniene, A. Kibarskis, A. Kirkutis, R. Marcinkus, I. Milvidaite, D. Vasiliauskas, J. C A Aalders, W. A J Bruggeling, P. J. De Feyter, M. J. De Leeuw, D. E P De Waard, G. J. De Weerd, C. De Zwaan, R. Dijkgraaf, H. T. Droste, M. P. Freericks, A. W. Hagoort-Kok, F. Hillebrand, W. T J Jap, G. M. Jochemsen, F. Kiemeney, P. J P Kuijer, H. F J Mannaerts, J. J. Piek, J. P M Saelman, F. D. Slob, W. C G Smits, M. J. Suttorp, T. B. Tan, G. J. Van Beek, L. F M Van Den Merkhof, R. Van Der Heyden, M. W J Van Hessen, R. A M Van Langeveld, P. R. Van Nierop, F. J W Van Rey, M. J. Van Straalen, J. Vos, H. A. Werner, J. J C Westendorp, P. Achremczyk, J. Adamus, J. Baska, H. Bolinska-Soltysiak, R. Bubinski, L. Ceremuzynski, A. Cieslinski, D. Dariusz, P. Drozdowski, J. S. Dubiel, M. Galewicz, B. Halawa, M. Janion, K. Jaworska, I. Kaszewska, A. Kleinrok, Z. Kornacewicz-Jach, W. Krawczyk, R. Krynicki, M. Krzciuk, M. Krzeminska-Pakula, J. Kuch, J. Kuzniar, D. Liszewska-Pfejfer, K. Loboz-Grudzien, W. Musial, G. Opolski, S. Pasyk, W. Piwowarska, G. Pulkowski, W. Ruzyllo, A. Rynkiewicz, W. Sinkiewicz, M. Skura, S. Slowinski, W. Smielak-Korombel, R. Targonski, W. Templin, M. Tendera, W. Tracz, M. Trusz-Gluza, J. Wodniecki, M. Zalewski, E. Zinka, M. Carrageta, J. Coelho Gil, R. Ferreira, A. Leitao Marques, C. M. Santos Andrade, R. Seabra-Gomes, V. Bada, M. Belicova, A. Dukat, G. Kaliska, G. Kamensky, K. Micko, Z. Mikes, M. Palinsky, D. Pella, B. Renker, I. Riecansky, P. Sefara, G. Sojka, P. Sulej, M. Szakacs, J. M. Aguirre Salcedo, N. Alonso Orcajo, P. Ancillo Garcia, J. M. Auge Sanpera, J. Ayuela Azcarate, J. L. Bardaji Mayor, V. Bertomeu Martinez, J. L. Blanco Coronado, F. Bosa Ojeda, R. Bros Caimari, J. Bruguera Cortada, J. Caparros Valderrama, A. Del Rio Ligorit, J. S. Espinosa Caliani, F. Fernandez Aviles, J. J. Garcia Guerrero, D. Garcia Lopez, E. Gonzalez Cocina, C. Guallar Urena, L. Jodar Lorente, V. Lopez Garcia-Aranda, C. Macaya De Miguel, J. Maroto Montero, P. Martinez Romero, I. Mate Benito, F. Navarro Lopez, F. Noriega Peiro, J. Olague De Ros, J. Orellana Mas, M. A. Paz Bermejo, L. J. Placer Peralta, L. Rodriguez Padial, A. Salvador Sanz, J. Segui Bonnin, E. Simarro Martin, F. Valles Belsue, S. Ekdahl, L. Forslund, H. Ohlin, M. Pieper, T. Moccetti, E. Acartürk, D. Guzelsoy, O. Özsaruhan, C. Turkoglu, A. A J Adgey, A. Ahsan, M. Al-Khafaji, S. G. Ball, J. Birkhead, N. Boon, M. Brack, A. Bridges, M. Buchalter, B. Calder, R. A. Cooke, L. Corr, R. Cowell, N. P. Curzen, C. Davidson, J. Davies, M. A. De Belder, L. Dhiya, J. C. Doig, I. N. Findlay, C. M. Francis, J. M. Glancy, T. W. Greenwood, P. Groves, A. S. Hall, G. Hamilton, I. Haq, R. Hillman, W. Hubbard, I. Hudson, I. Hutton, C. Ilsley, M. Innes, M. James, K. Jennings, G. Johnston, C. J H Jones, M. Joy, P. Keeling, J. Kooner, C. Lawson, R. D. Levy, G. Lip, B. Mclachlan, H. E. Montgomery, C. A. Morley, D. L. Murdoch, R. Muthusamy, G. D G Oakley, W. Penny, R. Percival, J. Purvis, M. P. Pye, D. Ramsdale, D. H. Roberts, A. Rozkovec, A. M. Salmassi, S. Saltissi, S. Sardar, L. M. Shapiro, P. M. Schofield, J. Stephens, C. Shakespeare, S. Srivastava, J. W. Swan, G. Tildesley, C. Travill, P. R. Wilkinson, M. D. Fratacci, G. Lerebours, J. Deckers

Research output: Contribution to journalArticle

1811 Scopus citations

Abstract

Background: Treatment with angiotensin-converting-enzyme (ACE) inhibitors reduces the rate of cardiovascular events among patients with left-ventricular dysfunction and those at high risk of such events. We assessed whether the ACE inhibitor perindopril reduced cardiovascular risk in a low-risk population with stable coronary heart disease and no apparent heart failure. Methods: We recruited patients from October, 1997, to June, 2000. 13 655 patients were registered with previous myocardial infarction (64%), angiographic evidence of coronary artery disease (61%), coronary revascularisation (55%), or a positive stress test only (5%). After a run-in period of 4 weeks, in which all patients received perindopril, 12 218 patients were randomly assigned perindopril 8 mg once daily (n=6110), or matching placebo (n=6108). The mean follow-up was 4.2 years, and the primary endpoint was cardiovascular death, myocardial infarction, or cardiac arrest. Analysis was by intention to treat. Findings: Mean age of patients was 60 years (SD 9), 85% were male, 92% were taking platelet inhibitors, 62% β blockers, and 58% lipid-lowering therapy. 603 (10%) placebo and 488 (8%) perindopril patients experienced the primary endpoint, which yields a 20% relative risk reduction (95% CI 9-29, p=0.0003) with perindopril. These benefits were consistent in all predefined subgroups and secondary endpoints. Perindopril was well tolerated. Interpretation: Among patients with stable coronary heart disease without apparent heart failure, perindopril can significantly improve outcome. About 50 patients need to be treated for a period of 4 years to prevent one major cardiovascular event. Treatment with perindopril, on top of other preventive medications, should be considered in all patients with coronary heart disease.

Original languageEnglish (US)
Pages (from-to)782-788
Number of pages7
JournalLancet
Volume362
Issue number9386
DOIs
StatePublished - Sep 6 2003

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    Fox, K. M., Bertrand, M., Ferrari, R., Remme, W. J., Simoons, M. L., Simoons, M., Bassand, J. P., Aldershvile, J., Hildebrandt, P., Cokkinos, D., Toutouzas, P., Eha, J., Erhardt, L., Erikssen, J., Grybauskas, P., Kalnins, U., Karsch, K., Sechtem, U., Keltai, M., ... Deckers, J. (2003). Efficacy of perindopril in reduction of cardiovascular events among patients with stable coronary artery disease: Randomised, double-blind, placebo-controlled, multicentre trial (the EUROPA study). Lancet, 362(9386), 782-788. https://doi.org/10.1016/S0140-6736(03)14286-9