CAPRIE Steering Committee.
Lancet (London, England). Date of publication 1996 Nov 16;volume 348(9038):1329-39.
1. Lancet. 1996 Nov 16;348(9038):1329-39.
A randomised, blinded, trial of clopidogrel versus aspirin in patients at risk of
ischaemic events (CAPRIE). CAPRIE Steering Committee.
CAPRIE Steering Committee.
Collaborators: Gent M, Beaumont D, Blanchard J, Bousser MG, Coffman J, Easton JD,
Hampton JR, Harker LA, Janzon L, Kusmierek JJ, Panak E, Roberts RS, Shannon JS,
Sicurella J, Tognoni G, Tool EJ, Verstraete M, Warlow C, Verstraete M, Easton JD,
Bousser MG, Cairns JA, Chesebro JH, Hampton JR, von der Lippe G, Ross Russell RW,
Wolf PA, Boissel JP, Friedman L, Fuster V, Harrison MG, Pocock S, Weksler BB,
Gent M, Foster G, Lewis G, Lychak T, Nelson HL, Roberts RS, Sicurella J,
Sicurella J, Stewart C, Szechtman B, Chrolavicius S, Copland I, Jedrzojawski B,
McCreadie F, Wilkinson L, Vonderveehn S, Boissel JP, Boutitie F, Beaumont D,
Perdriset G, Thizon de Gualle I, Hoek J, Besnier MO, Boddy A, Brooker D, Derzko
G, Jones A, Metzinger C, Novack J, Pratt S, Roome D, Schulhof JP, Vallee E,
Valtier D, Bastida E, Coy L, Creek R, Destelle G, Döberl T, de la Forest-Divonne
N, Gallo G, Garcia A, Geudelin B, Hundt F, Hylkema R, Vanhove P, Amalfitano N,
Cabala K, Caniglia J, Duval I, Forgie L, Neiss AC, Wesseling T, Plehn JF, Kennedy
SJ, Zwolak RM, Reeves A, McDaniel MD, MacDonald GJ, Murphy C, Howes PS, Cornell
LK, Hynes ML, Jackson CM, Lyden PD, Rothrock JF, Hye RJ, Dittrich HC, Kelly NM,
Kerridge CM, Chippendale T, Lobatz M, Diamond E, Schim J, Sadoff M, Logan W, Auer
A, Hamilton W, Frere R, Schroer S, Wilcox M, Naeger C, Harbison JW, Makhoul R,
Taylor JR, Felton WL 3rd, Lee HM, Massey-Makhoul K, Browne KF, Tyson GS, Pineiro
E, Brenner AS, Ford RA, Reddy PJ, Owens P, Heinsimer J, Richter K, Markowski K,
Lentini T, Howell L, Colfer HT, Rynbrandt DJ, Wendt CD, Wilmot M, Stone B,
Touchon R, Briley D, Adkins L, Roe K, Harless C, DeWood MA, Skidmore JA, Randall
JM, Davenport J, Farmer C, Hanson S, Kuo LC, Brown P, DesJardins J, Halpern N,
Talbot W, Schainfeld R, Rosenfield K, Isber JM, Grall E, Lanza S, Walker PA,
Ivanhoe RJ, Milunski MR, Kereiakes DJ, Abbottsmith CW, Lausten DA, Helgason CM,
Glover V, Gnutek T, Clark WM, Coull BM, Harrison E, Suh JT, McBride JW, Foster B,
Vittum K, Lauer NY, Adornato BT, Adornato MK, Fisher M, Ameriso SF, Scicli A,
Starling MR, Petrusha JA, Devlin WH, Suter CC, Tucci J, Stewart SH, Sadowsky C,
Stone R, Tuchman M, Massin EK, Anderson HV, Harlan M, Abrams J, Timm C, Rosenberg
G, Hiatt WR, Regensteiner JG, Bauer T, Frey JL, Darbonne C, Marlor L, Haire WD,
Stephens LC, Kotulak GD, Iteld B, VanderStappen A, Neuman V, Kleiman N, Bushman
L, Fischer A, Clark WM, Harrison E, Moon H, Klassen AC, Berman ME, Sufit R,
Biller J, Olin JW, Pirzada CA, Medical VA, Hershey LA, Burch K, Castaldo J, Jenny
D, Wohlberg C, Gaines K, Cape C, Gupta SK, Landa RA, Norcross SR, Culebras A,
Pastor DC, Fairman RM, Zakulec S, Sutton JM, McCullough T, Fenster PE, Feinberg
WM, Pellegrino RG, Jeffers C, Smith WB, Vargas R, McCormick T, Ramadan NM, Levine
SR, Hirsch AT, Wasserman AG, Nys A, Breslin DJ, Labib SB, Woodhead G, Matzura TM,
Dunlap S, Goodman MA, Cappelli J, Stein P, Nadamanee K, Havranek E, Weinberger J,
Lava NS, Horowitz S, Byer J, Wentworth D, Dexter JD, Bonnett A, Vetrovec GW,
O'Brien RP, Easton JD, Wilterdink JL, Gelber DA, Hemberger S, Sherman D, Rogers
D, Alberts MJ, McClenny C, Weeks KD, Whisnant D, D'Alton J, Doolittle H, Siller
KA, Hass WK, Grines C, Timmis G, Gorelick PB, Robinson D, Lumsden AB, MacDonald
J, Hughes RL, Noonan V, Goldberg G, Costello R, Mohiuddin S, Stengel L, Frankel
MR, Braimah J, Creager MA, Baum P, Cooke JP, Ma A, Babikian VL, O'Neal MA, Mirsen
T, Bruegel C, Coffman JD, Brindley DC, Mick M, Korenman SG, Brass LM, Asher SW,
Halperin JL, Schlesinger R, Gacioch GM, Couch JR Jr, Skolnick BE, Ware MS,
Anderson J, Knepper L, Victor M, Ball S, Gurley JC, Jessup M, Elkayam U, Hughes
WG, Fraser JA, Potvin EA, McMillan J, Grierson J, Hartwick N, Musclow S, Thompson
A, Mewett J, Sivan R, Turpie AG, Morino S, Siguenza M, Blakely JA, Styling S,
Balleza L, Beanlands DS, Garrard L, Morgan K, Ruddy T, Morris AL, Anderson BA,
Arneja AS, Carter SA, Daniels V, McEwen B, Ricci AJ, Swan JH, Goode JE, Selby DA,
Bozek B, Shuaib A, Yeung M, Press M, Walston LL, Fung AY, Henning H, Taylor DC,
Abbey H, Davies C, Saunders L, Tanser PH, Feldman D, Sullivan B, Sayles MJ, Kent
E, Connolly SJ, Coletta E, Carruthers V, Hui W, Klinke P, Brass N, Kvill L,
Cusson J, Van Nguyen P, Marchand L, Roy S, Blair JF, Wellington JL, Rody K,
Poloni S, Myers MG, Morgan CD, Parsons P, Lecours R, Patanaude JV, Turcotte C,
Gutelius JR, Pattenden R, Gagnon RM, Racine N, Roy C, Harris K, Lovell M, Teal
PA, Bloomer JL, Thompson CR, Wong M, Sladen JG, MacDonald K, Heinrich D, Houde G,
Nadeau C, Talbot P, Pagé A, Verdant A, Smilovitch M, Racine N, Steinmetz O,
Simard D, Benguigui C, Ouellet C, LeBrun LH, Desrochers MP, Finnie K, McCreery S,
Kostuk WJ, Pflugfelder PW, Oskalns R, Bonet JF, Ilott K, McConnell J, Ruel M,
Primeau L, Phillips S, Coleman-Kamphuis L, Leclerc JR, Solymoss S, Côté R,
Bourque F, Lee TK, Kvill L, Bernstein V, Doyle L, Timothee JR, Chebayeb R,
Lefkowitz C, Hambly P, Klein GM, Robertson M, Bayer N, Couse P, Norris JW, Medel
MJ, Sevitt B, Fitzsimons J, Fitchett D, Serpa A, Marr D, Ouellet B, Bellavance A,
Pryse-Phillips W, Howse DC, Rabkin SW, McCans J, Brandjes DP, Büller HR, Dÿkema
AR, Kromhout JG, Lawson JA, Peters RJ, van der Sande JJ, Stam J, Blok LM, Jenner
Y, Ternede O, Lens J, Bollen EC, Welten RJ, Termeulen P, Hollanders WP, Lok DJ,
Groeneveld H, Bouwens LH, Tietge FC, van der Velden EC, Bruggink-André PW, van
Iersel GJ, Seegers J, van Vliet AC, van der Sar P, Verhoog BD, van der Sar de
Nooijer SH, Verhoog-Nijhuis I, Franke CL, Koehler PJ, van der Meer J, van Os JS,
van der Heijden M, van Wijk LM, Kragten JA, de Warrimont-Henquet J, Feld R, Van
Gemert HM, Dippel DW, Koudstaal PJ, Vanneste JA, Linssen WH, Kruisdijk JJ, Visser
J, Van Gool TF, Vooges J, De Vries AC, Klinkert P, Bartlema KA, Banga JD,
Niemeijer-Kanters SD, de Groot MG, Moll FL, Sybrandy R, Buth J, Schol FP, Donders
RC, Algra A, Pop GA, van der Heijden R, Knippenberg B, Sier JC, Berqvist D,
Karacagil S, Eriksson I, Bowald S, Holmberg A, Ljungman C, Westman B, Sivenius J,
Puranen J, Karinen A, Onatsu J, Salmenperä T, Kalinen M, Kaste M, Tatlisumak T,
Soinne L, Kallela M, Kotila M, Hartford M, Herlitz J, Karlson BW, Strömblad SO,
Olofsson BO, Strand T, Kristensen B, Malm J, Melin JH, Virtanen M, Olli T,
Lindgärde F, Pessah-Rasmussen H, Rendell M, Ericsson UB, Sahlman A, Savolainen H,
Rämö J, Lehtonen J, Hillbom ME, Reunanen M, Turkka J, Ylönen K, Peltola T,
Juvonen T, Koskela E, Erkinheimo J, Ängquist KA, Hedberg B, Arnerlov C, Rissanon
A, Murros K, Idänpään-Heikkilä U, Honka L, Heikkilä J, Tiensuu T, Boberg J,
Berggren AL, Thompson PL, Yu ET, Bradshaw PJ, Cooke PA, Gordon SP, Loh KS,
McQuillan B, Moshiri MM, Cross DB, Egerton WS, Walker PJ, Codd CA, Kreuter DA,
Cox S, Naik D, Cavaye DM, Harel MC, Horowitz J, Rowe C, Stewart S, Boundy K,
Stringer CF, Anderson JL, Coller D, Aylward P, Anderson C, Burns R, Schultz D,
Waddy P, Walsh J, Davies L, Harris JP, Wetzlar A, McDougall A, Sieunarine K,
Cremer P, Donnan GA, Tonkin A, Levi C, Hanlan J, Ellery F, White HD, Hamer AW,
Kapadia V, Ramanathan K, Taylor RR, Hankey G, Brooks M, Young T, McInerney M,
Sansom J, Thomson R, Spaulding C, Cutforth R, Thomson A, Salem HH, Coughlin P,
Campbell TJ, Lord RS, O'Sullivan D, Corrigan C, D'Arcy S, Anderson NE, Charleston
AJ, Davis SM, Gerraty R, Bett N, Hewson DJ, Kester RC, Scott DJ, Berridge DC,
Kent PJ, Thornton CA, Sykes H, Bennett S, Blakey D, Brooksby WP, Johnston RT,
Brack M, Hampton JR, Vowden P, Gough MJ, Hooper R, Gough M, Hanley SP, MacAskill
M, Miles J, Waywell C, Mucklow JC, Davis C, Harper P, Cooke K, Lowe G, Shaw B,
McKillop J, Dormandy JA, Chaudhry H, Evans J, Bamford JM, Blundell S, Venables G,
Doyle C, Shearman CP, Crow A, Dennis M, Sandercock P, Brown MM, Rogers J, Boyle
RM, Wiseman BS, Humphrey PR, Prentice CR, Moccetti T, Pasotti E, Sessa F,
Bertolini A, Rossi A, Del A, Malacrida R, Moccetti D, Besomi G, Mattle HP, Eicher
Vella E, Maurer D, Rihs F, Hoffmann U, Bollinger A, Franzeck UK, Mahler F, Do D,
Baumgartner I, Weder B, Bönig L, Ludin HP, Bogousslavsky J, Maeder-Ingvar M,
Regli F, Kappenberger L, Depairon M, Bizzini G, Beretta-Piccoli C,
Elshater-Zanetti F, Guffi C, Bertel O, Deseö T, Gmuer W, Bounameaux H, Wicky J,
Desmarais S, Vogt P, Fellay D, Rhyner K, Wojtyna W, Bonetti T, Brunner J, Jäger
KA, von Planta I, Noseda G, Pugliesi A, Pons-Giudici L, Meier B, Evéquoz D,
Schmidt D, Keel HS, Heinrich D, Follath F, Brunner HP, Caduff B, Wirth M,
Vuilliomenet A, Savcic M, Hürlimann U, Bosshard E, Hacke W, Brandt T, Wildermuth
S, Ringleb P, Busse O, Straeten V, Zeuner K, Vielhaber S, Tettenborn B, Krämer G,
Allardt A, Schmitt-Henco E, Diener HC, Schrader V, Nebe J, Pilger E, Doder A,
Gürtl B, Diehm C, Gomer M, Jansen T, Kömpf D, Kaps M, Vidal-Langwasser M,
Hennerici M, Daffertshofer M, Schminke U, Osterhues HH, Fischer A, Rupprecht HJ,
Borkowski U, Rudofsky G, Rescher A, Schwerdt H, Hammer B, Voss R, Grebe M, Rieger
H, Grobe R, Theiss W, Schaub F, Neumann FJ, Lutilsky L, Aichner FT, Schmidauer C,
Erdlenbruch K, Mórsdorf BS, Hornig CR, Moulin T, Chavot D, Autret A, Lucas C,
Leys D, Henon H, Chedru F, Ameri A, Dunand JF, Dambrine P, Gabriel A, Labaki F,
Tran-Tranh X, Jouannon C, Durup F, Pagès M, Blard JM, Giroud M, Menassa M, Zuber
M, Mas JL, Hommel M, Besson G, Laurian C, Mathieu JF, Geraud G, Larrue V,
Ben-Hamda K, Fumey R, Guiraud-Chaumeil B, Chollet F, Pathé M, Zannier-Marzari D,
Chabriat H, Amarenco P, Pinel JF, Beaune J, Pichard JB, Medvedowsky A, Becker F,
Terriat B, Woimant F, Cathelineau G, Martin Jadraque I, López Sendon JL, Gonzales
Maqueda I, Roldan Rabadan I, Cruz Fernández JM, López Garcia V, Ros Die E,
Gonzáles Rios J, Del Foco O, Chamorro A, Alday M, Matias-Guiu J, Gracia F, Pomar
Moya-Prats JL, Mestres CA, Jiménez Cossio JA, Riera de Cubas L, Barreiro Tella P,
Diez Tejedor E, Cunha L, Goncalves AF, Ferro MA, Barbosa V, Santiago D, Ferro JM,
Melo TP, Oliveira V, Pinto AN, Bordalo-Sá AL, Ferreira D, Tuna JL, Providência L,
Morais J, Pimenta A, Van de Werf F, Luyten A, Luys C, Blecic SA, Van Blercom NG,
Hildebrand JG, Sadzot B, Franck G, Brohet C, Huyberechts D, Zicot M, Petermans J,
Duprez DA, Clement DL, Verhaeghe R, Peerlinck K, De Reuck J, Bosschaerts T,
Wautrecht JC, Coccheri S, Fortunato G, Catalano M, Libretti A, Carolei A,
Mearelli S, Gresele P, Selli L, Nenci GG, Morini M, Cortellaro M, Chierchia SL,
Luca Messa G.
Comment in
Lancet. 1997 Feb 1;349(9048):354; author reply 356.
Lancet. 1997 Feb 1;349(9048):354; author reply 356.
Lancet. 1997 Feb 1;349(9048):354-5; author reply 356.
Lancet. 1997 Feb 1;349(9048):355; author reply 356.
Lancet. 1997 Feb 1;349(9048):355-6.
Lancet. 1997 Mar 15;349(9054):806-7.
BACKGROUND: Many clinical trials have evaluated the benefit of long-term use of
antiplatelet drugs in reducing the risk of clinical thrombotic events. Aspirin
and ticlopidine have been shown to be effective, but both have potentially
serious adverse effects. Clopidogrel, a new thienopyridine derivative similar to
ticlopidine, is an inhibitor of platelet aggregation induced by adenosine
diphosphate.
METHODS: CAPRIE was a randomised, blinded, international trial designed to assess
the relative efficacy of clopidogrel (75 mg once daily) and aspirin (325 mg once
daily) in reducing the risk of a composite outcome cluster of ischaemic stroke,
myocardial infarction, or vascular death; their relative safety was also
assessed. The population studied comprised subgroups of patients with
atherosclerotic vascular disease manifested as either recent ischaemic stroke,
recent myocardial infarction, or symptomatic peripheral arterial disease.
Patients were followed for 1 to 3 years.
FINDINGS: 19,185 patients, with more than 6300 in each of the clinical subgroups,
were recruited over 3 years, with a mean follow-up of 1.91 years. There were 1960
first events included in the outcome cluster on which an intention-to-treat
analysis showed that patients treated with clopidogrel had an annual 5.32% risk
of ischaemic stroke, myocardial infarction, or vascular death compared with 5.83%
with aspirin. These rates reflect a statistically significant (p = 0.043)
relative-risk reduction of 8.7% in favour of clopidogrel (95% Cl 0.3-16.5).
Corresponding on-treatment analysis yielded a relative-risk reduction of 9.4%.
There were no major differences in terms of safety. Reported adverse experiences
in the clopidogrel and aspirin groups judged to be severe included rash (0.26% vs
0.10%), diarrhoea (0.23% vs 0.11%), upper gastrointestinal discomfort (0.97% vs
1.22%), intracranial haemorrhage (0.33% vs 0.47%), and gastrointestinal
haemorrhage (0.52% vs 0.72%), respectively. There were ten (0.10%) patients in
the clopidogrel group with significant reductions in neutrophils (< 1.2 x
10(9)/L) and 16 (0.17%) in the aspirin group.
INTERPRETATION: Long-term administration of clopidogrel to patients with
atherosclerotic vascular disease is more effective than aspirin in reducing the
combined risk of ischaemic stroke, myocardial infarction, or vascular death. The
overall safety profile of clopidogrel is at least as good as that of medium-dose
aspirin.
DOI: 10.1016/s0140-6736(96)09457-3
PMID: 8918275 [Indexed for MEDLINE]
