Cardiorenal end points in a trial of aliskiren for type 2 diabetes.
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Serval ID
serval:BIB_AA678180CBF9
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Cardiorenal end points in a trial of aliskiren for type 2 diabetes.
Journal
New England Journal of Medicine
Working group(s)
ALTITUDE Investigators
Contributor(s)
Viberti G., Lachin JM., Zinman B., Pedersen TR., Villamil AS., Juncos L., Prager R., Verpooten G., Zanella MT., Leiter L., Pan C., Wang H., Botero R., Cifkova R., Christiansen JS., Groop PH., Marre M., Haller H., Nickenig G., Siamopoulos K., Gero L., Maggioni A., Remuzzi G., Katayama SS., Kim SG., Petrulioniene Z., Lok D., Kooy A., Jorde R., Medina F., Polonia J., Wong KS., Dukat A., Rayner BL., Ruilope L., Weiss L., Wuethrich R., Sheu W., Sritara P., Comlekci A., Bilous R., Toto R., Jamerson K., Carillo E., Juncos L., Orias M., Kuschnir E., Rusculleda M., Garcia S., Farias E., Lema L., Hominal M., Montaña O., Sala J., Diaz M., Piskorz D., Vita N., Litwak L., Sinay I., Marin M., Massari P., Majul C., Aizemberg D., Azize GM., Bartolacci I., Reboredo A., Vico M., Milesi R., Sessa H., Wassermann A., Margulis F., Zangroniz P., Watschinger B., Prager R., Toplak H., Paulweber B., Drexel H., Francesconi C., Foeger B., Mayer G., Braun RK., Brath H., Gaal LV., Niepen PV., Persu A., Vercammen C., Vriese AD., Coucke F., Mathieu C., Fery F., Treille S., Meeus G., Acker KV., Scheen A., Tits J., Ruige J., Krzesinski JM., Hollanders G., Liénart F., Dendale P., Quinonez M., Arnouts P., Vanuytsel J., Zanella M., Mion D.<Suffix>Jr</Suffix> , Forti A., Almeida F., Cunha R., de Paula RB. , Brandao A., Rocha J., Krieger E., Feitosa G., Saraiva J., Martin J., Hissa MN., Schmid H., Felicio J., Sgarbi J., Oigman W., Bowering K., Garceau C., Berlingieri JC., Weisnagel SJ., Hardin P., Powell C., Turcot R., Muirhead N., Aronson R., Barima YT., Steele AW., Pandey S., Woo V., Cha J., Dattani D., Godin C., Gupta M., Leiter L., Saunders K., Tellier G., Ting R., Tobe S., Chouinard G., Schlosser R., Khandwala H., Ekoe JM., Harris SB., Pichette V., Lachance P., Ooi TC., Tildesley H., Barrett B., Cournoyer S., Lu J., Zhang H., Liu X., Yan S., Qi X., Li Q., Li H., Lv X., Yang J., Sun N., Xia W., Wang N., Tong N., Mei C., Gu S., Zhang J., Chen X., Li L., Su B., Wang L., Qiu M., Wu X., Liu Z., Jia W., Xu G., Dong J., Zhu D., Zhang M., Yan J., Liu B., Chen J., Fu J., Yan L., Zhan X., Zhong L., Yang T., Ma J., Xu M., Xu X., Shi B., Ji Q., Zhong H., He R., Yuan Z., Zhou Z., Lin H., Yang W., Ke Y., Li Q., Hong T., Franco C., Casas L., Triana A., Botero R., Jaramillo C., Hernandez E., Barrera C., Blanco D., Stipal R., Widimsky P., Dohnalova L., Komroskova M., Kvapil M., Belobradkova J., Tesar V., Cifkova R., Vodnansky P., Kocourkova B., Christiansen JS., Lervang HH., Perrild H., Rossing P., Oestergaard O., Juhl H., Thorsteinsson B., Snorgaard O., Urhammer S., Egstrup K., Tikkanen T., Helin K., Rinne J., Lahtela J., Strand J., Valtonen E., Saari M., Kananen K., Savela K., Marre M., Blacher J., Aldigier JC., Zaoui P., Fauvel JP., Gouet D., Valensi PE., Charpentier G., Marechaud R., Penfornis A., Ovize M., Kovalchuck AA., Haller H., Dellanna F., Schoen N., Groeschel W., Eickhoff F., Hanefeld M., Merke J., Rambausek M., Zimmermann U., Stuetz W., Vosskuehler A., Hevendehl G., Schax U., Lehmann G., Haack A., Hilgenberg J., Klausmann G., Adelberger V., Gessner S., Fiesselmann A., Oerter E., Hohenstatt T., Groeschel A., Behnke T., Sisting RT., Schoch D., Bieler T., Schleyer S., Altes U., Klepzig C., Rudofsky G., Mueller G., Burkhardt F., Reschke K., Senftleber I., Wiesweg CK., Herrmann HJ., Brandstetter R., Segner A., Nickenig G., Schmitt H., Rippert R., Goebel R., Schreibmueller F., Pencz I., Ott P., Siamopoulos K., Migdalis I., Pappas S., Pagkalos E., Yalouris A., Tsapas A., Maltezos E., Tentolouris N., Papadakis I., Ioannidis G., Goumenos D., Corona V., Gonzalez R., Haase F., Monterroso V., Sánchez V., Turcios E., Wyss F., Arango JL., Bako B., Deak L., Dömötör E., Dudas M., Fulop T., Kiss I., Koranyi L., Lengyel Z., Nyirati G., Oroszlan T., Aniko S., Vörös P., Kapocsi J., Wittmann I., Paragh G., Abraham G., Tandon N., Thomas N., Mohan V., Sahay R., Sethi B., Rao V., Kumar S., Chowdhury S., Dharmalingam M., Seshiah V., Bantwal G., Viswanathan V., Yajnik C., Adhikari 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Medina B., Medina F., Herrada B., Saavedra A., Polonia DJ., Providencia DL., Carvalho D., Vasconcelos MP., da Silva GF. , Branco P., Gil DV., da Costa AG. , da Silva PM. , Arez L., Martins L., Birne R., Dzuponova J., Surovcikova M., Culak J., Dukat A., Filipova S., Andre I., Stevlik J., Uhliar R., Fabryova L., Benacka J., Koleny D., Szentivanyi M., Spisak V., Pella D., Pastrnakova E., Martinka E., Chua T., Wong KS., Lau T., Ng TG., Yeoh LY., Bhana SA., Rayner B., Wellmann H., Amod A., Ranjith N., Ahmed F., Rheeder P., Makan H., Naicker P., Podgorski G., De Teresa E., Olivan J., Fernandez VL., Povedano ST., Terns M., Ricart W., Gonzalez JM., Fernandez P., Parreño Lde T., Redon J., Parra J., Calvo C., Lopez I., Puig JG., Calle A., Garcia JC., Lopez JM., Jimenez ML., Fraile B., Perez JS., Nadal JJ., Guija E., Calviño J., Barrios V., Iglesias JN., Armario P., Garcia M., Aranda P., Brotons C., Ruilope L., Gomez P., Catelao AM., Cusachs AR., Sarro M., Martinez V., dell Valle MH. , Trias F., Comas A., Salvador N., Martinez F., Hernandez F., Martinez J., Mateos C., Peral JL., Tolosana J., Sobrino J., Isart J., Vizcaino J., Vega FF., Zamorano JL., Bacariza M., Soubriet A., Fernández-Cruz A., Querejeta R., Leira VM., Iglesias FE., Ibrik O., Martin D., Nanclares MS., Mediavilla JD., Galceran JM., Lopez A., Muros T., Pascual J., Casalla F., Tornero F., Fernandez G., Weiss L., Pettersson P., Olsen H., Franke F., Stroembom U., Furuland H., Larnefelt H., Allemann Y., Krapf R., Wuethrich R., Gerber P., Munger R., Hayoz D., Graf HJ., Burnier M., Petrillo A., Batt R., Constam EN., Moccetti T., Bianda T., Rickli H., Bulliard C., Wu KD., Lin SH., Wu CJ., Sheu WH., Su SL., Chen SC., Chou CW., Lee CT., Yang TC., Chen HC., Sritara P., Sukonthasarn A., Sriratanasathavorn C., Eiam-Ong S., Supasyndh O., Chanchairujira T., Kitiyakara C., Comlekci A., Arici M., Usalan C., Guneri S., Koc M., Kalender B., Ates K., Gurgun C., Araz M., Demirbas B., Biernacki W., Calvert J., Eavis P., Kerrane J., Litchfield J., Middleton A., Roberts J., Simpson H., Charles H., Jardine A., Fisher M., Banerjee D., Gallen I., Gnudi L., Harvey J., O'Hare P., Vora J., Winocour P., Soran H., Browne D., Darko D., Mancebo JG., de Roa ER. , Antepara N., Carrillo E., Berrizbeitia M., Guevara L., Pernalete N., Ontiveros C., Zigrang W., Blakney E., Rosenblit P., Weinstein R., Klaff L., Lipetz R., Busick E., Tung P., Cooperman M., Michael S., Sun CH., Hart T., Maddux A., Bowden R., East C., Arakaki R., Villafuerte B., Mamish Z., Mendez R., Connery L., Nour K., Wynne A., Busch R., Zamora B., Sachson R., Prasad J., Lasala G., Smith M., Fitz-Patrick D., Ruiz-Rivera L., Barranco E., Solomon R., Woolley A., Brown C., Freedman Z., Schmidt S., Pollock J., Ruddy M., Toto R., Kopyt NP., Bazzi A., Horowitz B., Feng W., Wahl T., Duprez D., Gilbert J., Steigerwalt S., Jacqmein J., Gorton S., Allison J.<Suffix>3rd</Suffix> , Pino J., Lock J., Leimbach W., Anderson J., Beacom M., Craig W., Gorson D., Kerstein H., Segal S., Downey H., Ledger G., McGill J., Gabriel J., Nolen T., Levinson L., Williams T., Levenson D., Lerman S., Minehart C., Agarwal N., Verma S., Valitutto M., Demetry K., Mersey J., Koeper D., Fanti P., Eng G., Jamerson K., Grimm R., Fagan T., Bajaj M., Katz L., Portnay G., Altschuller A., Desai V., Bilazarian S., Ipp E., Rodelas R., Burstein D., Berg J., Velez J., Lund R., Rekhi A., Martin E., Martin J., Robertson D., Singh N., Narayan P., Moustafa M., Lanier D., Seidner M., Phillips A., Vaughters B., Sprague A., Swartz S., Lopez R., Kumar J., Bressler P., Sadler L., Wise J., Kilbane A.
ISSN
1533-4406 (Electronic)
ISSN-L
0028-4793
Publication state
Published
Issued date
12/2012
Peer-reviewed
Oui
Volume
367
Number
23
Pages
2204-2213
Language
english
Notes
Publication types: Journal Article ; Randomized Controlled Trial ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
Publication Status: ppublish
Abstract
BACKGROUND: This study was undertaken to determine whether use of the direct renin inhibitor aliskiren would reduce cardiovascular and renal events in patients with type 2 diabetes and chronic kidney disease, cardiovascular disease, or both.
METHODS: In a double-blind fashion, we randomly assigned 8561 patients to aliskiren (300 mg daily) or placebo as an adjunct to an angiotensin-converting-enzyme inhibitor or an angiotensin-receptor blocker. The primary end point was a composite of the time to cardiovascular death or a first occurrence of cardiac arrest with resuscitation; nonfatal myocardial infarction; nonfatal stroke; unplanned hospitalization for heart failure; end-stage renal disease, death attributable to kidney failure, or the need for renal-replacement therapy with no dialysis or transplantation available or initiated; or doubling of the baseline serum creatinine level.
RESULTS: The trial was stopped prematurely after the second interim efficacy analysis. After a median follow-up of 32.9 months, the primary end point had occurred in 783 patients (18.3%) assigned to aliskiren as compared with 732 (17.1%) assigned to placebo (hazard ratio, 1.08; 95% confidence interval [CI], 0.98 to 1.20; P=0.12). Effects on secondary renal end points were similar. Systolic and diastolic blood pressures were lower with aliskiren (between-group differences, 1.3 and 0.6 mm Hg, respectively) and the mean reduction in the urinary albumin-to-creatinine ratio was greater (between-group difference, 14 percentage points; 95% CI, 11 to 17). The proportion of patients with hyperkalemia (serum potassium level, ≥6 mmol per liter) was significantly higher in the aliskiren group than in the placebo group (11.2% vs. 7.2%), as was the proportion with reported hypotension (12.1% vs. 8.3%) (P<0.001 for both comparisons).
CONCLUSIONS: The addition of aliskiren to standard therapy with renin-angiotensin system blockade in patients with type 2 diabetes who are at high risk for cardiovascular and renal events is not supported by these data and may even be harmful. (Funded by Novartis; ALTITUDE ClinicalTrials.gov number, NCT00549757.).
METHODS: In a double-blind fashion, we randomly assigned 8561 patients to aliskiren (300 mg daily) or placebo as an adjunct to an angiotensin-converting-enzyme inhibitor or an angiotensin-receptor blocker. The primary end point was a composite of the time to cardiovascular death or a first occurrence of cardiac arrest with resuscitation; nonfatal myocardial infarction; nonfatal stroke; unplanned hospitalization for heart failure; end-stage renal disease, death attributable to kidney failure, or the need for renal-replacement therapy with no dialysis or transplantation available or initiated; or doubling of the baseline serum creatinine level.
RESULTS: The trial was stopped prematurely after the second interim efficacy analysis. After a median follow-up of 32.9 months, the primary end point had occurred in 783 patients (18.3%) assigned to aliskiren as compared with 732 (17.1%) assigned to placebo (hazard ratio, 1.08; 95% confidence interval [CI], 0.98 to 1.20; P=0.12). Effects on secondary renal end points were similar. Systolic and diastolic blood pressures were lower with aliskiren (between-group differences, 1.3 and 0.6 mm Hg, respectively) and the mean reduction in the urinary albumin-to-creatinine ratio was greater (between-group difference, 14 percentage points; 95% CI, 11 to 17). The proportion of patients with hyperkalemia (serum potassium level, ≥6 mmol per liter) was significantly higher in the aliskiren group than in the placebo group (11.2% vs. 7.2%), as was the proportion with reported hypotension (12.1% vs. 8.3%) (P<0.001 for both comparisons).
CONCLUSIONS: The addition of aliskiren to standard therapy with renin-angiotensin system blockade in patients with type 2 diabetes who are at high risk for cardiovascular and renal events is not supported by these data and may even be harmful. (Funded by Novartis; ALTITUDE ClinicalTrials.gov number, NCT00549757.).
Keywords
Aged, Amides/adverse effects, Amides/therapeutic use, Angiotensin Receptor Antagonists/therapeutic use, Angiotensin-Converting Enzyme Inhibitors/therapeutic use, Antihypertensive Agents/adverse effects, Antihypertensive Agents/therapeutic use, Cardiovascular Diseases/epidemiology, Cardiovascular Diseases/mortality, Diabetes Mellitus, Type 2/complications, Diabetes Mellitus, Type 2/drug therapy, Double-Blind Method, Drug Therapy, Combination, Female, Follow-Up Studies, Fumarates/adverse effects, Fumarates/therapeutic use, Humans, Hyperkalemia/chemically induced, Hypokalemia, Kidney Diseases/epidemiology, Kidney Diseases/etiology, Male, Middle Aged, Patient Dropouts, Renin/antagonists & inhibitors, Treatment Failure
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18/01/2013 16:13
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20/08/2019 15:14
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