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N Engl J Med. 2008 Dec 4;359(23):2417-28. doi: 10.1056/NEJMoa0806182.

Benazepril plus amlodipine or hydrochlorothiazide for hypertension in high-risk patients.

Collaborators (554)

Jamerson K, Weber M, Dahlöf B, Bakris G, Pitt B, Velazquez E, Weir M, Egan B, Devereux R, Nesbitt S, Cushman W, Wright J, Ofili E, Papademetriou V, Massie B, Kjeldsen S, Ostergren J, Ibsen H, Tuomilehto J, Black HR, Julius S, Oparil S, Lindholm LH, Fisher L, Pfeffer M, Solomon S, Mahaffey K, Lewis E, Finn P, Anavekar N, Kenchaiah S, Sampson U, Egan B, Blank R, Bhushan R, Moore H, Jackson D, Hargrove J, Cushman W, Basile J, Headley D, Ahmad A, Betts M, Mounir M, Rios M, Tavarez J, Rivera L, Barranco E, Sosa-Padilla M, Colon-Ortiz P, Ortiz-Carrasquillo R, Sutter G, Ocampo E, Iskander S, Joe L, Sarma R, Anderson J, Antonishen M, Betz W, Suresh D, Bounds C, Brandon D, Castaldo R, Chin J, Cohen S, Collins G, Corbelli J, Curatola D, Folkerth S, Cox S, Stewart J, Hack T, Hagan M, Hart T, Haught H, Herring C, Holcomb T, Hordes A, Kereiakes D, Klein T, Koren M, Kushner F, Lipetz R, Hassel C, Mazza J, Mahan G, Mazzone F, McCartney M, Messina N 3rd, Miller D, Nuss M, Nwasuruba C, Pool J, Roth E, Rubino J, Connelly S, Schactman B, Sugimoto D, Traboulssi M, Turtizin S, Tuttle K, Vande Merwe D, Wilhoit G, Williams R, Wright R, Harizi R, Woolley A, Millstine D, Seaworth J, Berk M, Samuels B, Raval P, Willard J, Yates S, Drummond W, Richards M, Fenton I, Fintel D, Rivera E, Rohr C, Saba S, Fattal P, Conard S, Rapo S, Hermany P, East C, Reddix M, Gill S, Seidner M, Smith S, Iteld B, Vanderburg E, Sutherland J, Morton J, Darwin C, Hershon K, Andrews C, Bareis C, Lang C, Quigley J, Turner A, Stoker J, McCullough P, Goss S, Marshall M, Acklin J, Furlow J, Shepherd A, Segall N, Howard T, Chacko B, West J, Maddux A, Bouchard A, Pollock S, Sall K, Cacchione P, Leimbach W, Sobel E, Kreis S, Lopez J, Marino J 3rd, Mollen M, Schmidt S, Kenton D, Coy K, Clower J, Bazzi A, Ortiz-Butcher C, Frais M, Nesbitt S, Brown D, Mohar D, Russell L, Horowitz B, Underberg J, Williams H, Nuttall A, LaFata J, Diener C, Wright J, Craig J, Agarwal A, Noss M, Bussey H, Pettyjohn F, Brown C, Kruszewski D, Dreyfus J, Ramirez H, Ong Y, McNicol D, Greenberg B, Segal S, Deichmann R, Haidar A, Kusnick B, Smothers R, Axe H, Popeil L, Prashad R, Belber A, Fischell T, Sheehan K, Reeder V, Baier C, Bright D, Tse A, Craig W, Schultz R, Ervin J, Jenkins L, Ransome-Kuti O, Lunde N, Williams G, McGee J, Gassner L, Grainer S, White W, Race J, Marks E, Bittar N, Weiss R, Cuellar J, Maurer M, Browning W Jr, Trevino M, Goldstein M, Quartner J, Munuswamy K, Zamora B, Cass A, Donovan D, Abboud H, Teguh C, Diederich P, Cottiero R, Altschul L, Blanchard D, Nunamaker J, Shealy N, Drehobl M, Bartkowiak A, Langhorne W 3rd, Kaufmann R, Rama P, Jerome S, Simpson A, Ong S, Papademetriou V, Wiener V, Fagan T, Gelernt M, Kramer J, Colan D, Charani K, Coleman H, Nanna M, Lang J, Lebeau D, Prabhu R, Bibler M, Loh I, Maccaro P, Mukherjee S, Porterfield J, Germino W, Singh N, Prasad J, Bernstein J, Ben-Yehuda O, Christensen J, Sklaver N, Dart R, Benjamin S, Brobyn T, Munger M, Williams D, Plantholt S, Hartman I, Flack J, Lawless J, Palac R, Gabriel J, Feng W, Garrett D, Howard V, Tamayo R, Graf R, Kinstrey T, Soufer J, McGettigan J, Zee P, Felton W, Linden D, Gardner T, Sadiq R, Ross D, Shalev Y, Houston M, Scott D, Mezitis N, Thompson D, Nevins B, Fiacco P, McConn S, Wynne A, Ledesma G, Glover R, Townsend R, Nadeau D, Canadas R, Marple R, Jain A, Arzola F, Herrod J, Milburn J, Changlani M, Fail P, Denys B, Kobayashi J, Morley J, Helton D, Cox W, Porter J, Allison J, Mitchell M, Patlola R, Abel P, Amin M, Kolettis E, Ellis J, Kogan A, Portz M, Desai V, Schulman C, Mersey J, Barajas A, Hejeebu S, Yarows S, Seigel P, Littlejohn T 3rd, Miller A, Snell P, Carr A, Pudi K, Zigrang W, Cucher F, Singh B, Brautigam D, Steigerwalt S, Benton R, Bloch M, Wendschuh P, Narayan P, Oates S, Greengold R, Khoshaba A, Carr K, Civitarese L, Toth P, Fredrickson S, Kayota S, Deac D, Dean G, Shetter T, Harper W, Marek J, Bertolino J, Mirka A, Shanes J, Smallow S, Schwartz S, Bloomgarden R, Akbar S, Wingfield W, Areephanthu A, Smith R, Guevara A, McNeff J, Henry B, Dunmyer S, Ofili E, Hartley P, Austin B, Wilmer C, Hamad M, Farrington C, Raad G, Chasen C, Kozinn M, Lupu J, Dionisopoulos P, Cohen K, Gutmann J, Thieneman A, Singh S, Japra R, Neutel J, Glaser L, Cheung D, Kaplan R, Weinstein R, Mion-Bet S, Feller M, Miller J, Höglund C, Tengmark B, Johansen H, Henningsen N, Mölstad C, Svensson E, Gonn A, Lundgren W, Holmberg G, Fröberg L, Rickman M, Nemeczek C, Zetterberg S, Bergholtz T, Lundholm M, Ulvenstam G, Nordlund T, Blomberg A, Ericsson U, Ekesbo R, Sundqvist B, Larsson K, Lönneborg L, Ostgård P, Borgencrantz B, Romberg K, Dahlén G, Wallén T, Gustafsson I, Nilsson D, Hedberg G, Björkman B, Rönmark P, Olsson P, Theobald H, Sjöberg A, Frisk M, Henriksson A, Johansson S, Norring A, Carlsson I, Määgi E, Lindholm C, Hellerstedt S, Svensson J, Iacobeus B, Nielsen J, Tillberg C, Tygesén G, Jennersjö P, Berglund O, Johansson S, Jansson R, Tenhunen A, Ehn L, Thingwall G, Akerman L, Sjöberg L, Bjerkeryd J, Hansen J, Ellström J, Mörlid L, Löw-Larsen B, Pettersson P, Petersson U, Rahm T, Lager I, Roslin G, Mannerroos P, Andersson J, Herlitz J, Benson L, Kastlund B, Henningson L, Holmqvist J, Nilsson K, Karlsson G, Paulsson L, Eketorps V, Hedner T, Andersson O, Bokemark L, Dahlqvist A, Asplund G, Rosengren M, Pettersson P, Jaedig S, Ejvinsson G, Olsson T, Nordberg J, Lövoll T, Hollertz U, Skoog P, Vedvik A, Fosse S, Rössås L, Skjelvan G, Moen H, Tomala T, Werner E, Lund K, Fauske J, Torvik D, Jacobsen T, Brunstad O, Kontny F, Langaker K, Pindborg T, Larsen J, Wøldike J, Christensen O, Mølenberg K, Schultz P, Tuxen C, Nielsen P, Mortensen F, Rickers H, Petersen J, Lederballe O, Garne S, Roed S, Kronstedt J, Søndergaard J, Nielsen T, Ralfkjaer N, Kølendorf K, Hansen H, Lemming L, Kaiser-Nielsen P, Tuomilehto J, Strandberg A, Junnila S, Icen R, Sarti C, Airas J, Jääskivi M, Litmanen H, Tuominen M, Kantola I, Sallinen O, Hällberg V, Antikainen R, Korhonen P, Palomäki A, Rantonen J, Kallioniemi V, Ebeling P, Latva-Nevala A.

Author information

  • 1Division of Cardiovascular Medicine, University of Michigan Health System, 24 Frank Lloyd Wright Dr., Lobby M, Ann Arbor, MI 48106, USA. emarshal@umich.edu

Abstract

BACKGROUND:

The optimal combination drug therapy for hypertension is not established, although current U.S. guidelines recommend inclusion of a diuretic. We hypothesized that treatment with the combination of an angiotensin-converting-enzyme (ACE) inhibitor and a dihydropyridine calcium-channel blocker would be more effective in reducing the rate of cardiovascular events than treatment with an ACE inhibitor plus a thiazide diuretic.

METHODS:

In a randomized, double-blind trial, we assigned 11,506 patients with hypertension who were at high risk for cardiovascular events to receive treatment with either benazepril plus amlodipine or benazepril plus hydrochlorothiazide. The primary end point was the composite of death from cardiovascular causes, nonfatal myocardial infarction, nonfatal stroke, hospitalization for angina, resuscitation after sudden cardiac arrest, and coronary revascularization.

RESULTS:

The baseline characteristics of the two groups were similar. The trial was terminated early after a mean follow-up of 36 months, when the boundary of the prespecified stopping rule was exceeded. Mean blood pressures after dose adjustment were 131.6/73.3 mm Hg in the benazepril-amlodipine group and 132.5/74.4 mm Hg in the benazepril-hydrochlorothiazide group. There were 552 primary-outcome events in the benazepril-amlodipine group (9.6%) and 679 in the benazepril-hydrochlorothiazide group (11.8%), representing an absolute risk reduction with benazepril-amlodipine therapy of 2.2% and a relative risk reduction of 19.6% (hazard ratio, 0.80, 95% confidence interval [CI], 0.72 to 0.90; P<0.001). For the secondary end point of death from cardiovascular causes, nonfatal myocardial infarction, and nonfatal stroke, the hazard ratio was 0.79 (95% CI, 0.67 to 0.92; P=0.002). Rates of adverse events were consistent with those observed from clinical experience with the study drugs.

CONCLUSIONS:

The benazepril-amlodipine combination was superior to the benazepril-hydrochlorothiazide combination in reducing cardiovascular events in patients with hypertension who were at high risk for such events. (ClinicalTrials.gov number, NCT00170950.)

2008 Massachusetts Medical Society

Comment in

PMID:
19052124
[PubMed - indexed for MEDLINE]
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