Cardiorenal end points in a trial of aliskiren for type 2 diabetes (original) (raw)
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.).
Cardiorenal end points in a trial of aliskiren for type 2 diabetes
Parving HH;Brenner BM;McMurray JJ;de Zeeuw D;Haffner SM;Solomon SD;Chaturvedi N;Persson F;Desai AS;Nicolaides M;Richard A;Xiang Z;Brunel P;Pfeffer MA;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. Jr;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 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GA;Sekiguchi M;Aoki S;Ogawa Y;Seino H;Onishi Y;Tojo A;Narimiya M;Iwaita Y;Takeda H;Shimizu H;Yamada T;Kojima S;Zushi S;Kaneko S;Matsumoto A;Kajiyama S;Fujita H;Shikata K;Tone A;Matsubayashi S;Tanaka S;Sekigami T;Tatsukawa Y;Abe N;Kawahara K;Kasahara H;Maeda Y;Suzuki Y;Okamoto H;Tachi K;Yamada K;Uzu T;Itou T;Fukui T;Kim S;Kim Y;Cho W;Kwak I;Chae D;Oh H;Ha S;Shin Y;Cha D;Kim Y;Kim S;Kang S;Lim C;Song J;Kwon Y;Badariene J;Labutiniene IP;Zabuliene L;Poteliuniene V;Miglinas M;Kooy A;van den Meiracker AH;Gregoor PJ;Luik AJ;van Loon BJ;Feenstra HJ;Kaasjager HA;Viergever PP;Woittiez AJ;van Bemmel T;Lieverse AG;Simsek S;Gaillard CA;van der Zwaan C;Lok DJ;Spiering W;Nierop PR;Baggen MG;Leendert RJ;de Jong A;Leurs PB;Vincent HH;Wins EH;Voors AA;Ronner E;Heeg JE;van Hal JM;Boermans T;Feis WL;Mostard G;Bakker RC;Dunselman PH;Jorde R;Skeie S;Istad H;Skjelvan G;Gronert J;Tomala T;Gudnason S;Torvik DT;Risberg K;Abedini S;Cabrera W;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. 3rd;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.
2012-01-01
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.).
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2318/129755
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