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N Engl J Med. 2016 May 26;374(21):2009-20. doi: 10.1056/NEJMoa1600175. Epub 2016 Apr 2.

Blood-Pressure Lowering in Intermediate-Risk Persons without Cardiovascular Disease.

Collaborators (440)

Alzogaray M, Aparici M, Berli M, Bevacqua M, Bustamante Labarta M, Bustos B, Caccavo A, Candiello A, Carignano M, Carrillo N, Carro N, Cartasegna L, Casali W, Cassettari A, Centeno M, Cuello J, Cusimano S, Cuneo C, Duran R, Damonte C, De Landaluc M, De Martino E, Diez R, Duran R, Fernandez A, Ferrari A, Forti L, Galello M, Garcia C, Giachello F, Garrido M, Gonzalez M, Guerlloy F, Guerrero R, Hrabar A, Imposti H, Hominal M, Liniado G, Lanchiotti P, Laugle C, Liniado G, Litvak MR, Longhi A, Luciardi H, Mackinnon I, Marino J, Manzano R, Merlo B, Milesi R, Molina de Salazar DI, Mulazzi C, Nemi S, Orio S, Pelaggage M, Raimondi S, Rodino L, Rodriguez A, Rodriguez C, Rodriguez D, Sago L, Sala J, Sanchez A, Sanchez R, Santos D, Schygiel P, Sernia V, Smith T, Sokn F, Soso L, Trivi M, Vico M, Vilamajo O, Villamil A, Vogel D, Zaidman C, Abhayaratna W, Canalese J, Krum H, Patel A, Alves AR Jr, Alves CB, Ayoub JC, Bergoli LC, Blacher MG, Bodanese LC, Braga JC, Brasil CK, Costa MK, Costa OM, de Faria DG, Del Monaco MI, Fabian Restelatto L, Filho F, Franco RJ, Furtado MV, Leaes PE, Maia LN, MarinNeto JA, Martins AP, Mattar ET, Melo CM, Mothe FS, Oliveira GB, Oliveira LF, Pelloso E, Polanczyk CA, Rosa PR, Sales SO, Saraiva JF, Schmidt A, Silva VS, Sousa AC, Valle A, Wiehe M, Abramson B, Anand S, Aw J, Baxter W, Berlingieri J, Cha J, Chaulk R, Chetty T, Dagenais G, Dattani D, Delage F, Dion D, Dominguez M, Gallo R, Glendinning K, Goldman H, Gosselin G, Greenspoon A, Hungly Q, Juneau M, Keegan P, Kelly A, Kilby D, Lavoie M, Leiter LA, Lonn E, Magloire P, Mehta P, Mercante N, Miscescu H, Moran G, Nawaz S, Nigam A, Pang P, Papp E, Petrella R, Poirier C, Rabasa-Lhoret R, Rizvi Q, Saulnier D, Sharma M, Sohal P, Stern S, Tobe S, Walsh P, Ward R, Weeks A, Woo V, Yellin J, Zuliani P, Bai XJ, Dong LG, Feng JZ, Fu P, Gao P, Gao MM, Ge H, Hu SP, Hua Q, Li DJ, Liu ZD, Liu YJ, Liu XL, Liu LH, Liu FY, Lu FH, Lv T, Ma H, Ma SP, Man RH, Shen Y, Shi JF, Sun XD, Wang B, Wang SY, Wang YN, Wang YQ, Wei YJ, Yang HS, Yang XC, Yu JH, Yu K, Yu LT, Zhang B, Zhang F, Zhang HY, Zhang L, Zhang W, Zhao JG, Zhao Y, Zhong BX, Accini J, Aroca G, Arcos E, Accini-Valencia M, Casanova M, Celemin C, Coronel BJ, Cotes C, Cure C, Duarte A, Escobar D, Figueredo M, Garcia H, Garcia L, Grisales M, Hernandez Z, Molina de Salazar D, Martinez K, Nino Castellanos B, Diego-Olite M, Ospina Rendon N, Posada I, Quintero A, Quiros F, Sanchez G, Sotomayor A, Suarez M, Urina M, Adamkova V, Cifkova R, Ferkl R, Galovcova M, Hartman J, Jozifova M, Linhart K, Linhart T, Moravcikova D, Nussbaumerova B, Plachy M, Rosolova H, Seifert B, Soucek M, Duarte Vera Y, Espinel M, Lopez-Jaramillo M, McDermont J, Penaherrera E, Plascencia F, Pow-Chon-Long F, Tettamanti D, Bajnok L, Baranyi E, Bartfai E, Bod E, Bodis B, Czuriga I, Huber E, Mezosi E, Poor F, Somos E, Tarjanyi Z, Tatrai T, Tomcsanyi J, Vertes A, Zsary A, Aggarwal DK, Alexander KG, Aman S, Arun, Ayyar V, Balaji Y, Balasubramanian E, Bantwal G, Bhalvishiya Y, Bosco B, Chidambaram N, Dabra A, Daniel S, Deshpande N, Devendra HR, Ghoshroy D, Gnanasekaran S, Gupta R, Gutti MZ, Jayakumar P, Joshi G, Joshi S, Kalantri SP, Kapoor A, Khan A, Khedar R, Kishore J, Kumar A, Kumar S, Kumaravel, Manjunath AR, Mehta K, Mohan V, Murthy S, Nambiar A, Narendra J, Paul SK, Qureshi MA, Rajasekaran S, Ramu M, Ranka RL, Rangadham K, Roy S, Sathyanarayan MR, Selvam K, Sethuraman JP, Shabhasane D, Shivaraj K, Shunmugvavelu M, Sidhu G, Singh B, Singh R, Srinivas A, Srinivas J, Srinivasulu B, Thomas N, Umarani R, Varghese K, Varma S, Yelvatkar S, Biton A, Goldhaber A, Ivri S, Shapiro I, Shveydel E, Shveydel N, Tsalihin D, Vinker S, Yosefy H, Kim S, Choe KH, Ambigga D, Aris MA, Ghapar KA, Krishnan C, Mahadasa P, Maizatullifah M, Mazapuspavina Y, Ramanathan L, Shah A, Yusoff K, Bonarius JH, De Jong A, DeRuiter Z, DeVos R, Dirkse HA, Drenth E, Ferguson H, Jansen R, Mevissen H, Rol H, Schilder A, Spelt I, VanLeeuwen P, Abola M, Co H, Loyola A, Mercado J, Morales D, Padua L, Palileo L, Patanao A, Rogelio G, Roxas A, Sulit D, Tang-Manga A, Tumanan-Mendoza B, Boytsov S, Chukaeva I, Karpov Y, Kisliak O, Kobalava Z, Ledyacva A, Lopatin Y, Nedogoda S, Solovieva M, Tsoma V, Tyurina T, Hranai M, Badat A, Gerntholtz T, Sliwa K, Al-Khalili F, Carlberg B, Dotevall A, Nilsson P, Olsson A, Rosengren A, Soderberg S, Khunti K, Loke I, Toff WD, Artomov D, Babanina T, Bagriy A, Chobotko G, Danyliuk S, Doretska N, Dorovska O, Dovgan N, Dzyak G, Glushko L, Gorbas I, Ilashchuk T, Karapetyan K, Karavanska I, Khimion L, Khorsun A, Kononenko L, Kuryata O, Kvasha O, Lazareva S, Loktyev D, Lysenko G, Martynyuk V, Miroshnchenko N, Onyschenko O, Petryk N, Pivovarova S, Rakytskay I, Sapozhnychenko L, Smymova I, Soya O, Tashchuk V, Turubarova-Leunova N, Vasilyeva L, Velichko N, Yagensky A, Zborovskyy S, Zhurba S.

Author information

1
From the Population Health Research Institute, Hamilton Health Sciences (E.M.L., J.B., R.M., J.P., J.W., H.J., S.Y.), the Department of Medicine (E.M.L., R.M., S.Y.), the School of Rehabilitation Science (J.B.), and the Department of Clinical Epidemiology and Biostatistics (J.P.), McMaster University, Hamilton, ON, Li Ka Shing Knowledge Institute and Keenan Research Centre for Biomedical Science, St. Michael's Hospital, University of Toronto, Toronto (L.A.L.), and Institut Universitaire de Cardiologie et Pneumologie de Québec, Université Laval, Quebec, QC (G.D.) - all in Canada; Fundacion Oftalmológica de Santander and Instituto Masira, Medical School, Universidad de Santander, Bucaramanga (P.L.-J.), and University of Caldas and Institución Prestadora de Salud Internistas de Caldas, Manizales (D.I.M.S.) - both in Colombia; Fu Wai Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing (J.Z., L.L.); St. John's Research Institute (P.P., D.X.) and St. John's Medical College (D.X.), Bangalore, India; Instituto Cardiovascular de Rosario, Rosario, Argentina (R.D.); Hatter Institute for Cardiovascular Research in Africa, Department of Medicine, University of Cape Town, Soweto Cardiovascular Research Group, Cape Town, South Africa (K.S.); College of Medicine, University of the Philippines, Manila (A.D.); Dante Pazzanese Institute of Cardiology (A.A.) and HCor-Heart Hospital (L.S.P.) - both in São Paulo; Hungarian Institute of Cardiology, Semmelweis University, Budapest, Hungary (K. Keltai, M.K.); Institute of Clinical Cardiology in the Russian Cardiology Research Complex, Moscow (I.C.); the Department of Cardiology, Academic Medical Center, Amsterdam (R.J.G.P.); the Department of Medical Sciences, Cardiology, Clinical Research Center, Uppsala University, Uppsala, Sweden (C.H.); Universiti Teknologi Majlis Amansh Rakyat, Selayang, and University College Sedaya International University, Kuala Lumpur (K.Y.) - both in Malaysia; Lady Davis Ca

Abstract

BACKGROUND:

Antihypertensive therapy reduces the risk of cardiovascular events among high-risk persons and among those with a systolic blood pressure of 160 mm Hg or higher, but its role in persons at intermediate risk and with lower blood pressure is unclear.

METHODS:

In one comparison from a 2-by-2 factorial trial, we randomly assigned 12,705 participants at intermediate risk who did not have cardiovascular disease to receive either candesartan at a dose of 16 mg per day plus hydrochlorothiazide at a dose of 12.5 mg per day or placebo. The first coprimary outcome was the composite of death from cardiovascular causes, nonfatal myocardial infarction, or nonfatal stroke; the second coprimary outcome additionally included resuscitated cardiac arrest, heart failure, and revascularization. The median follow-up was 5.6 years.

RESULTS:

The mean blood pressure of the participants at baseline was 138.1/81.9 mm Hg; the decrease in blood pressure was 6.0/3.0 mm Hg greater in the active-treatment group than in the placebo group. The first coprimary outcome occurred in 260 participants (4.1%) in the active-treatment group and in 279 (4.4%) in the placebo group (hazard ratio, 0.93; 95% confidence interval [CI], 0.79 to 1.10; P=0.40); the second coprimary outcome occurred in 312 participants (4.9%) and 328 participants (5.2%), respectively (hazard ratio, 0.95; 95% CI, 0.81 to 1.11; P=0.51). In one of the three prespecified hypothesis-based subgroups, participants in the subgroup for the upper third of systolic blood pressure (>143.5 mm Hg) who were in the active-treatment group had significantly lower rates of the first and second coprimary outcomes than those in the placebo group; effects were neutral in the middle and lower thirds (P=0.02 and P=0.009, respectively, for trend in the two outcomes).

CONCLUSIONS:

Therapy with candesartan at a dose of 16 mg per day plus hydrochlorothiazide at a dose of 12.5 mg per day was not associated with a lower rate of major cardiovascular events than placebo among persons at intermediate risk who did not have cardiovascular disease. (Funded by the Canadian Institutes of Health Research and AstraZeneca; ClinicalTrials.gov number, NCT00468923.).

PMID:
27041480
DOI:
10.1056/NEJMoa1600175
[Indexed for MEDLINE]
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