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N Engl J Med. 2012 Aug 30;367(9):817-25. doi: 10.1056/NEJMoa1204133.

Effects of clopidogrel added to aspirin in patients with recent lacunar stroke.

Collaborators (467)

Benavente O, Hart R, Pergola P, Palacio S, Castro I, Farias A, Roldan A, Kase C, Gavras I, Lau H, Ogrodnik M, Allen N, Meissner I, Graves J, Herzig D, Covalt J, Meyer B, Jackson C, Gamble P, Kelly N, Warner J, Bell J, Demaerschalk B, Hogan M, Wochos D, Wieser J, Cleary B, Wood L, Hanna J, Zipp T, Bailey S, Cook D, Liskay A, Simcox D, Kappler J, Anderson D, Grimm R, Brauer D, Pettigrew C, Vaishnov A, Sawaya P, Fowler A, Hughes N, Rice J, Vanderpool K, Cruz-Flores S, Walden HD, Holzemer E, Santhakumar S, Van Stavern R, Flack J, Mada F, Wiseman D, Berlow E, Klinker J, Chiu D, Taylor A, Katz L, Coull B, Howard L, Malekniazi M, VanSkiver M, Bruck D, Redman S, Logan W, Carpenter D, Schroer S, Katramados A, Silver B, Yee J, Aiello K, Wilson K, McCarthy S, Dandapani B, Spies CP, Vasile C, Anthony B, Ferguson J, Krubel S, Synman A, Andrews N, Kirshner H, Sussman C, Brown D, Elkind M, Crew RJ, Radhakrishan J, Corporan TE, Diaz J, Aragon R, Slivka A, Spetie D, Agriesti J, Notstein P, Naritoku D, Zweifler R, Culpepper M, Parnell M, Yunker R, Boots K, Drinkard R, Backlin R, Benesch C, Bisognano J, Leonhardt A, Zentner J, Hildreth M, Johnson M, Liu Y, Goldsteen R, Blair A, Wright G, Gathua N, Book D, Eapen S, Grimm C, Blaney B, Rozman S, Gaertner L, Bradenburg E, Loomis L, Monarch-Cotton J, Ravavelli-Meyer J, Golembieski A, Burgin SW, Hollander J, Polashenski W, Wallace P, Weber C, Lutsep H, Girard D, Seisler K, Cingel M, Ross M, Stone R, Larsen D, Doherty A, Lefkowitz D, Pavel L, Buchheimer N, Vaughn S, Smith E, Satterfield J, Tirschwell D, Logar C, Ryan M, Schubert G, Tanzai P, Mirsen T, McAllister S, Bastien A, Niblack P, Frey J, Darbonne C, Karanjia P, Murali N, Dart R, Mancl K, Atkinson R, Lieberman R, Carter T, Zrelak P, Kenney N, Jacoby M, Jones D, DeFrancisco J, Hamm T, Romano J, Ortiz G, Lichtenberger Mdel C, Linas R, Kravet S, Alt J, Sundararajan S, Rahman M, Horvath T, Korosec D, Murphy C, Greenberg J, Lennihan L, King M, Tenteromano L, Frankel M, Doyle J, Braimah J, Pereira L, Ching M, Sawyer R, Parkes K, Conover C, Albakri E, Ramirez G, Segal S, Taylor K, Jackson J, Helgason K, Hillmann M, Ringel R, Fleming N, Mckown B, Cohen S, Jenders R, Singh R, La MT, Trinh K, Weinberger J, Wright L, Burch D, Horowitz R, Atlas S, Augustine S, Van Stavern R, Brown A, Serna J, Newgent J, Naylor J, Carpenter L, Warwick T, Stoltz S, Garcia R, Scheck M, Chadwick L, Fleck J, Weinberger M, Sears A, Fanale C, Neeper L, Fisk P, Cohen S, Sabry D, Phoenix R, Tong D, Garcia M, Mackey A, Morin J, Haché A, Lessard C, Côté R, Green L, Wadup L, Fontaine AM, Gubitz G, Rebello R, Dean T, Reidy Y, Sharma M, Stotts G, Clark H, Mortensen M, Sauve J, Sharma D, Savage M, Minuk J, Trudeau L, Schanz C, Berger L, Brunet S, Pontbriand J, Mainville M, Racicot D, Hill M, Fischer K, Cole-Kaskayne A, Keeney C, Shuab A, Khan K, Dean N, Herbert F, Kastelic K, Pretell EJ, Valdivia J, Pretell M, del Brutto O, Santibáñez R, Lara J, Zambrano M, Arauz A, Cervantes GA, Leyva A, Camacho I, Ruiz Sandoval JL, Salcido Vásquez E, Ruiz C, Cantú Brito C, Fernández M, Góngora-Rivera JF, Escamilla JM, Moxica J, Arciniega G, Gonzalez WJ, Matamala G, Goecke H, Parra M, Pozo J, Tapia J, Godoy IE, Valdes M, Estol C, Peralta C, Ellenberg A, Chezzio D, Fernández Pardal MM, Trimachi H, Bonardo P, Mazziotti J, Rey RC, Caruso G, Melamud L, Lepera S, Stilman AP, Ameriso S, Sánchez R, Bruera G, Moschini J, Ramírez MJ, Bueri JA, Sevilla S, de Ambrosi B, Marinsalta G, Rubio F, Krupinski Y, Carvajal A, Roquer J, Oliveras Serrano A, Jiménez Conde J, Rodríguez A, Romeral G, Arboix A, Pelegrí A, Blanco L, Cánovas Vergé D, Herrero JE, Gómez A, Blanco L, Leal JS, Castellanos M, Cruz V, Cepeda M, Gomis M, Arenillas J, Dávalos A, Suñol A, Reverté S, Martí-Villalta JL, Martínez S, Marín R, Castillo Sánchez J, Blanco González M, Rodríguez M, Jiménez I, Rodríguez J, Díez Tejedor E, Martínez P, Fuentes B, Soler Singla L, Balaguer E, Izquierdo J, Soler C, Armenteros M, Benavente O, Hart R, Pergola P, Roldan A, Benavente MF, White C, Robu C, Kelly C, Talbert R, Martinez E, Bazan C, Pergola G, Pearce L, Costello R, Jacova C, Camelia L, Mendoza C, Pratt B, Holliday S, McClure L, Coffey C, Szychowski J, Howard G, Katholi C, Zhang Y, Peri K, Allcorn C, Mailhot R, Irby L, Guyton F, Sewell MJ, Ringer R, Raisch D, Hunt D, Rubio F, Rosso CM, Martin A, Sanllorente M, Arabetti C, Fernández JL, Cremona MJ, Capece A, Benavente O, Hart R, Benavente M, Coffey C, Conwit R, McClure L, Pergola P, Roldan A, Szychowski J, Talbert R, Benavente O, Anderson D, Aruez A, Benavente M, Coffey C, Conwit R, Côté R, del Brutto O, Elkind M, Hart R, Kase C, McClure L, Moy C, Pergola P, Roldan A, Szychowski J, Talbert R, White C, White C, Benavente O, Benesch C, Coffey C, Conwit R, Graves J, Grimm R, Gubitz G, Holliday S, Lau H, Moy C, Pearce L, Szychowski J, Aguilar M, Sherman D, Nasco E, Blackshear J, Chung M, Fayad P, Gage B, Johnston C, Kernan W, Leira E, Merino J, Roman G, Sila C, Sung G, van Walraven C, Zweifler R, Stern B, Conwit R, Moy C, Welch K, Clarke W, Cutler J, Furie K, Johnston K, Mayo M.

Abstract

BACKGROUND:

Lacunar infarcts are a frequent type of stroke caused mainly by cerebral small-vessel disease. The effectiveness of antiplatelet therapy for secondary prevention has not been defined.

METHODS:

We conducted a double-blind, multicenter trial involving 3020 patients with recent symptomatic lacunar infarcts identified by magnetic resonance imaging. Patients were randomly assigned to receive 75 mg of clopidogrel or placebo daily; patients in both groups received 325 mg of aspirin daily. The primary outcome was any recurrent stroke, including ischemic stroke and intracranial hemorrhage.

RESULTS:

The participants had a mean age of 63 years, and 63% were men. After a mean follow-up of 3.4 years, the risk of recurrent stroke was not significantly reduced with aspirin and clopidogrel (dual antiplatelet therapy) (125 strokes; rate, 2.5% per year) as compared with aspirin alone (138 strokes, 2.7% per year) (hazard ratio, 0.92; 95% confidence interval [CI], 0.72 to 1.16), nor was the risk of recurrent ischemic stroke (hazard ratio, 0.82; 95% CI, 0.63 to 1.09) or disabling or fatal stroke (hazard ratio, 1.06; 95% CI, 0.69 to 1.64). The risk of major hemorrhage was almost doubled with dual antiplatelet therapy (105 hemorrhages, 2.1% per year) as compared with aspirin alone (56, 1.1% per year) (hazard ratio, 1.97; 95% CI, 1.41 to 2.71; P<0.001). Among classifiable recurrent ischemic strokes, 71% (133 of 187) were lacunar strokes. All-cause mortality was increased among patients assigned to receive dual antiplatelet therapy (77 deaths in the group receiving aspirin alone vs. 113 in the group receiving dual antiplatelet therapy) (hazard ratio, 1.52; 95% CI, 1.14 to 2.04; P=0.004); this difference was not accounted for by fatal hemorrhages (9 in the group receiving dual antiplatelet therapy vs. 4 in the group receiving aspirin alone).

CONCLUSIONS:

Among patients with recent lacunar strokes, the addition of clopidogrel to aspirin did not significantly reduce the risk of recurrent stroke and did significantly increase the risk of bleeding and death. (Funded by the National Institute of Neurological Disorders and Stroke and others; SPS3 ClinicalTrials.gov number, NCT00059306.).

PMID:
22931315
[PubMed - indexed for MEDLINE]
PMCID:
PMC4067036
Free PMC Article
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