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N Engl J Med. 2016 May 26;374(21):2032-43. doi: 10.1056/NEJMoa1600177. Epub 2016 Apr 2.

Blood-Pressure and Cholesterol Lowering in 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 (S.Y., E.L., J.B., R.M., J.P., H.J.), Department of Medicine (S.Y., E.L., R.M.), School of Rehabilitation Science (J.B.), 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; St. John's Research Institute (P.P., D.X.), and St. John's Medical College (D.X.), Bangalore, India; Fundacion Oftalmológica de Santander and Instituto Masira, Medical School, Universidad de Santander, Bucaramanga (P.L.-J.), and Universidad del Norte, Barranquilla (J.L.A.) - both in Colombia; Fu Wai Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing (J.Z., L.L.); Dante Pazzanese Institute of Cardiology (A.A.) and HCor-Heart Hospital (L.S.P.), Sao Paulo; Institute of Cardiology, Kiev, Ukraine (A.P.); Hungarian Institute of Cardiology, Semmelweis University, Budapest, Hungary (M.K., K. Keltai); Hatter Institute for Cardiovascular Research in Africa, Department of Medicine, University of Cape Town, Soweto Cardiovascular Research Group, Cape Town, South Africa (K.S.); 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 Carmel Medical Center, Ruth and Bruce Rappaport School of Medicine, Technion-Israel Institute of Technology, Haifa, Israel (B.S.L.); University Hospital Motol, Prague, Czech Repu

Abstract

BACKGROUND:

Elevated blood pressure and elevated low-density lipoprotein (LDL) cholesterol increase the risk of cardiovascular disease. Lowering both should reduce the risk of cardiovascular events substantially.

METHODS:

In a trial with 2-by-2 factorial design, we randomly assigned 12,705 participants at intermediate risk who did not have cardiovascular disease to rosuvastatin (10 mg per day) or placebo and to candesartan (16 mg per day) plus hydrochlorothiazide (12.5 mg per day) or placebo. In the analyses reported here, we compared the 3180 participants assigned to combined therapy (with rosuvastatin and the two antihypertensive agents) with the 3168 participants assigned to dual placebo. The first coprimary outcome was the composite of death from cardiovascular causes, nonfatal myocardial infarction, or nonfatal stroke, and the second coprimary outcome additionally included heart failure, cardiac arrest, or revascularization. The median follow-up was 5.6 years.

RESULTS:

The decrease in the LDL cholesterol level was 33.7 mg per deciliter (0.87 mmol per liter) greater in the combined-therapy group than in the dual-placebo group, and the decrease in systolic blood pressure was 6.2 mm Hg greater with combined therapy than with dual placebo. The first coprimary outcome occurred in 113 participants (3.6%) in the combined-therapy group and in 157 (5.0%) in the dual-placebo group (hazard ratio, 0.71; 95% confidence interval [CI], 0.56 to 0.90; P=0.005). The second coprimary outcome occurred in 136 participants (4.3%) and 187 participants (5.9%), respectively (hazard ratio, 0.72; 95% CI, 0.57 to 0.89; P=0.003). Muscle weakness and dizziness were more common in the combined-therapy group than in the dual-placebo group, but the overall rate of discontinuation of the trial regimen was similar in the two groups.

CONCLUSIONS:

The combination of rosuvastatin (10 mg per day), candesartan (16 mg per day), and hydrochlorothiazide (12.5 mg per day) was associated with a significantly lower rate of cardiovascular events than dual 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:
27039945
DOI:
10.1056/NEJMoa1600177
[Indexed for MEDLINE]
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