Collaborative overview of randomised trials of antiplatelet therapy - I: Prevention of death, myocardial infarction, and stroke by prolonged antiplatelet therapy in various categories of patients

R ALTMAN, L CARRERAS, R DIAZ, E FIGUEROA, E PAOLASSO, JC PARODI, JF CADE, G DONNAN, MJ EADIE, TP GAVAGHAN, EF OSULLIVAN, D PARKIN, JTG RENNY, C SILAGY, H VINAZZER, F ZEKERT, H ADRIAENSEN, JM BERTRANDHARDY, M BRAN, JL DAVIDJ DRICOT, E LAVENNEPARDONGE, R LIMET, A LOWENTHAL, M MORIAU, S SCHAPIRA, P SMETS, J SYMOENS, R VERHAEGHE, M VERSTRAETE, A ATALLAH, H BARNETT, R BATISTA, J BLAKELY, JA CAIRNS, R COTE, J CROUCH, G EVANS, JM FINDLAY, M GENT, Y LANGLOIS, J LECLERC, J NORRIS, GF PINEO, PJ POWERS, R ROBERTS, L SCHWARTZ, J SICURELLA, W TAYLOR, P THEROUX, AG TURPIE, RD WEISEL, J CUI, L LIU, J PIRK, C BAY, G BOYSEN, JB KNUDSEN, P PETERSEN, PS SORENSEN, HK TONNESEN, PT HARJOLA, JC ARCAN, B BALKAU, J BLANCHARD, JP BOISSEL, B BONEU, MG BOUSSER, M BROCHIER, M CLOAREC, G CRIBIER, M DECHAVANNE, P DROUIN, E ESCHWEGE, B GUIRAUDCHAUMEIL, R HUGONOT, A LEIZOROVICZ, Y LORIA, L MICHAT, J MIROUZE, E PANAK, J PASTEYER, A RASCOL, L REVOL, M ROY, J SELLES, G SLAMA, C STARKMAN, M TEULE, N THIBULT, M VERRY, FW ALBERT, K ANDRASSY, K BREDDIN, R ECKEL, A ENCKE, J FROHLICH, B HARTUNG, HW HEISS, H HESS, B HOFLING, D KRAUSE, G LATTA, H LINKE, D LOEW, R LORENZ, K MIDDLETON, G NOVAK, M OLDENDORF, N PFLUGER, D RAITHEL, R REUTER, G SCHETTLER, J SCHNITKER, W SCHOOP, H STIEGLER, K UBERLA, G VOGEL, M WEBER, WELBERS, E ZEITLER, G ARAPAKIS, T CHAN, CK MOK, R SZABO, NP MISRA, K REDDY, GA FITZGERALD, A APOLLONIO, F BALSANO, A BASELLINI, L CANDELISE, M CATALANO, N CIAVARELLA, G CIUFFETTI, S COCCHERI, M CORTELLARO, G CORVI, E. COTO, G DAVI, R DECATERINA, T DIPERRI, C FIESCHI, R GENTILE, L GREGORATTI, P GRESELE, M LAVEZZARI, A LIBRETTI, B MAGNANI, G NENCI, G PAGANO, C PATRONO, L PEDRINI, M PINI, P PRANDONI, F ROMEO, F ROVELLI, G RUDELLI, G RUVOLO, GP SIGNORINI, G TOGNONI, F VIOLI, T FUJIMORI, M KAGEYAMA, T KATSUMURA, S KITAMURA, K MAEDA, A SUZUKI, H TOHGI, S UCHIYAMA, H UTSUMI, AM GARCIA, A ALGRA, GJH DENOTTOLANDER, AJF KUPPER, J VANGIJN, H HART, LJ KAPPELLE, PJ KOUDSTAAL, T LEMMENS, J LODDER, M PANNEBAKKER, PW SERRUYS, A VANDENBELT, J VANDERMEER, AB VANDERVIJGH, FWA VERHEUGT, G VETH, J DALE, KA JOHANNESSEN, E THAULOW, P POPESCU, N TIBERIU, JRD AZNAR, E ESMATJES, P GUITERAS, J LASIERRA, P LOPEZTRIGO, A ORIOL, L POMAR, E ROCHA, FD SANCHEZ, J SANCHORIEGER, G SANZ, ULF BERGLUND, C BLOMSTRAND, M BOBERG, M BRITTON, CE ELWIN, C HELMERS, J HOLM, L JANZON, S JUULMOLLER, H MULEC, JE OLSSON, S PERSSON, G RASMANIS, A ROSEN, K SAMUELSSON, J SOREFF, N WAHLGREN, L WALLENTIN, HR BAUR, M BOKSLAG, A BOLLINGER, B MEIER, M PFISTERER, N PFLUGER, C SITTHIAMORN, EJ ACHESON, P APPLEBY, AW ASSCHER, A AUKLAND, C BAIGENT, S BALA, AH BARNETT, P BELL, S BEWS, GVR BORN, JP BRANAGAN, N BROOKS, MJ BROWN, NL BROWSE, R CAPILDEO, M CARMALT, AE CARTER, K.J. CHALMERS, M CLARKE, RJ CLARKE, CAC CLYNE, R COLLINS, ED COOKE, G COUTTS, DH COVE, PS CROWTHER, WF CUTHBERTSON, D DEBONO, C DICKERSON, JP DICKINSON, R DOLL, JA DORMANDY, D DUNBABIN, S ELL, P ELPHINSTONE, P ELWOOD, ENGLISHBY, B FARRELL, C FISKERSTRAND, M FLATHER, T FOLEY, T FOULDS, KM FOX, P FRANKS, H FRASER, T GARDECKI, M GAWEL, AE GENT, AH GERSHLICK, J GODWIN, M GOLDMAN, C GRAY, D GRAY, R GRAY, H HANDOLL, G HANKEY, MJG HARRISON, N HENDERSON, S HEPTINSTALL, SF HOBBIGER, EW JONES, NAG JONES, S JOST, D JULIAN, J KELLETT, RC KESTER, G LOWE, J MACKENZIE, CN MCCOLLUM, G MEAD, TW MEADE, D MENDELOW, JC MILLER, GK MORRIS, C NICHOL, M NOBLE, P.A. OBRIEN, M OGIER, S PARISH, MJ PARRY, R PETO, J POWELL, P POZZILLI, N QIZILBASH, A RAHMAN, SM RAJAH, DH RICHARDS, S RICHARDS, R RIPLEY, VC ROBERTS, FC ROSE, RWR RUSSELL, PC RUBIN, CV RUCKLEY, P SANDERCOCK, MDM SHAW, KM SHAW, JH SHELLEY, J SLATTERY, P SLEIGHT, SJ SMITH, P STEWARTLONG, PM SWEETNAM, MJB TANSEY, H TINDALL, J TURNEY, HM TYLER, NC VAREY, MP VESSEY, MD WALKER, MA WALKER, CP WARLOW, RG WILCOX, H WILLEMS, EH WOOD, E WYNJONES, HP ADAMS, B BARTON, RF BEDFORD, BL BICK, S BINGHAM, BG BROWN, T BRYANT, J BURING, CF CABOT, P CANNER, J CHESEBRO, OD CHRISMAN, GP CLAGETT, JA COLWELL, M DYKEN, D ELLIS, WS FIELDS, C FURBERG, Valentin FUSTER, S GOLDMAN, J GRANETT, RM GREEN, D GREEN, R HARDY, LA HARKER, WH HARRIS, RG HART, WK HASS, C HENNEKENS, D HILL, M HUME, MC IGLOE, G JOHNSON, S JONAS, G KNATTERUD, TR KOHLER, NJ LEMBO, D LEWIS, E LOCKHART, P MAJERUS, MT MCENANY, R MCKENNA, JL MEHTA, JS MEYER, B MOLONY, T MORITZ, DM NICOLOFF, G NYCZ, H ONO, GA PANTELY, SJ PHILLIPS, P RIDKER, JT ROBERTSON, R ROTHBART, EW SALZMAN, RD SAUTTER, RC SCHLANT, JA SCHOENBERGER, MV SENGEKONTACKET, G SHARMA, P STEELE, KP STEINNAGEL, J. Stratton, JM SULLIVAN, G TIMMIS, JF TOOLE, MD WALKER, S WEISMAN, CW WHITE, M WIRECKI, D WOMBOLT, R WONG, S YUSUF, K ZADINA, D ZUCKER

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Abstract

Objective-To determine the effects of ''prolonged'' antiplatelet therapy (that is, given for one month or more) on ''vascular events'' (non-fatal myocardial infarctions, non-fatal strokes, or vascular deaths) in various categories of patients.

Design-Overviews of 145 randomised trials of ''prolonged'' antiplatelet therapy versus control and 29 randomised comparisons between such antiplatelet regimens.

Setting-Randomised trials that could have been available by March 1990.

Subjects-Trials of antiplatelet therapy versus control included about 70 000 ''high risk'' patients (that is, with some vascular disease or other condition implying an increased risk of occlusive vascular disease) and 30 000 ''low risk'' subjects from the general population. Direct comparisons of different antiplatelet regimens involved about 10 000 high risk patients.

Results-In each of four main high risk categories of patients antiplatelet therapy was definitely protective. The percentages of patients suffering a vascular event among those allocated antiplatelet therapy versus appropriately adjusted control percentages (and mean scheduled treatment durations and net absolute benefits) were: (a) among about 20 000 patients with acute myocardial infarction, 10% antiplatelet therapy v 14% control (one month benefit about 40 vascular events avoided per 1000 patients treated (2P

Reductions in vascular events were about one quarter in each of these four main categories and were separately statistically significant in middle age and old age, in men and women, in hypertensive and normotensive patients, and in diabetic and nondiabetic patients. Taking all high risk patients together showed reductions of about one third in non-fatal myocardial infarction, about one third in non-fatal stroke, and about one sixth in vascular death (each 2P

Among low risk recipients of ''primary prevention'' a significant reduction of one third in non-fatal myocardial infarction was, however, accompanied by a non-significant increase in stroke. Furthermore, the absolute reduction in vascular events was much smaller than for high risk patients despite a much longer treatment period (4.4% antiplatelet therapy v 4.8% control; five year benefit only about four per 1000 patients treated) and was not significant (2P=0.09).

Conclusions-Among a much wider range of patients at high risk of occlusive vascular disease than is currently treated routinely, some years of antiplatelet therapy-with aspirin 75-325 mg/day or some other antiplatelet regimen (provided there are no contraindications)-offers worthwhile protection against myocardial infarction, stroke, and death. Significant benefit is evident not only among patients with unstable angina, suspected acute myocardial infarction, or a past history of myocardial infarction, stroke, or transient ischaemic attack, but also among many other categories of high risk patients (such as those having vascular procedures and those with stable angina or peripheral vascular disease). There is as yet, however, no clear evidence on the balance of risks and benefits of antiplatelet therapy in primary prevention among low risk subjects.

Original languageEnglish
Pages (from-to)81-100
Number of pages20
JournalBMJ: British Medical Journal
Volume308
Issue number6921
Publication statusPublished - 8 Jan 1994

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