Collaborative overview of randomised trials of antiplatelet therapy Prevention of death, myocardial infarction, and stroke by prolonged antiplatelet therapy in various categories of patients
Year: 1994
Type: article
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< 0.00001)); (b) among about 20 000 patients with a past history of myocardial infarction, 13% antiplatelet therapy v 17% control (two year benefit about 40/1000 (2P<0.00001)); (c) among about 10 000 patients with a past history of stroke or transient ischaemic attack, 18% antiplatelet therapy v 22% control (three year benefit about 40/1000 (2P<0.00001)); (d) among about 20 000 patients with some other relevant medical history (unstable angina, stable angina, vascular surgery, angioplasty, atrial fibrillation, valvular disease, peripheral vascular disease, etc), 9% v 14% in 4000 patients with unstable angina (six month benefit about 50/1000 (2P<0.00001)) and 6% v 8% in 16 000 other high risk patients (one year benefit about 20/1000 (2P<0.00001)). 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 non : diabetic 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<0.00001). There was no evidence that non-vascular deaths were increased, so in each of the four main high risk categories overall mortality was significantly reduced. The most widely tested antiplatelet regimen was “medium dose” (75-325 mg/day) aspirin. Doses throughout this range seemed similarly effective (although in an acute emergency it might be prudent to use an initial dose of 160-325 mg rather than about 75 mg). There was no appreciable evidence that either a higher aspirin dose or any other antiplatelet regimen was more effective than medium dose aspirin in preventing vascular events. The optimal duration of treatment for patients with a past history of myocardial infarction, stroke, or transient ischaemic attack could not be determined directly because most trials lasted only one, two, or three years (average about two years). Nevertheless, there was significant (2P<0.00001) further benefit between the end of year 1 and the end of year 3, suggesting that longer treatment might well be more effective. 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.
Source: BMJ
Authors: Robert Altman, L Carreras, Rubén Sierra Díaz, Efraín Bú Figueroa, Ernesto Paolasso, Juan C. Parodi, J. F. Cade, Geoffrey A. Donnan, Mervyn J. Eadie, T P Gavaghan, E. F. O'Sullivan, Donald Maxwell Parkin, Renny Jtg., C Silagy, H Vinazzer, F Zekert, H. Adriaensen, J. M. Bertrand-Hardy, M Bran, Jean‐Louis David, J. Dricot, E Lavenne-Pardonge, R Limet, A. Löwenthal, M Moriau, S Schapira, Peer Smets, J. Symoens, Raymond Verhaeghe, M Verstraete, Ana Atallah, Henry J.M. Barnett, Ruth Ester Assayag Batista, J.A. Blakely, John A. Cairns, Robert Côté, John Crouch, Gregory W. Evans, J. Max Findlay, Michael Gent, Yves Langlois, Jacques Leclerc, J. M. Norris, G F Pineo, Peter Powers, Robert Roberts, Lisa Barrie Schwartz, Jane Sicurella, W. Robert Taylor, Pierre Théroux, Alexander G. G. Turpie, R D Weisel, Jinghan Cui, L Liu, Jan Pirk, Curtis Bay, Gudrun Boysen, Jens Knudsen, Pernille Lykke Petersen, P S Sorensen, HAAVARD TØNNESEN, Pekka-T. Harjola, J.C. Arcan, B. Balkau, J Blanchard, Jean Boissel, B Boneu, Marie‐Germaine Bousser, M Brochier, M Cloarec, G. Alain Cribier, M Dechavanne, P Drouin, E Eschwège, B Guiraud-Chaumeil, R Hugonot, Alain Leizorovicz, Y Loria, L Michat, J Mirouze, E Panak, J Pastéyer, A Rascol, L Révol, M. Roy, Juana Sellés, G. Slama, C Starkman, M Teule, N Thibult, M. Verry, F Albert, K. Andrássy, K Breddin, Robert H. Eckel, A. Encke, Jiri Frohlich, Benno Hartung, H Heiss, H Hess, B. Höfling, Debra Krause, G. Latta, H Linke, D Loew, Rebecca Lorenz, K Middleton, Gerald Novak, M Oldendorf, N Pfluger, D. Raithel, R Reuter, Gotthard Schettler, J Schnitker, W Schoop, H. Stiegler, K. Überla, G. Vogel, MM Weber, I. Welbers, Emily P. Zeitler, G. Arapakis, Thomas Chan, Claire Mok, Renáta Szabó, Nilanjana Misra, Kumar B. Reddy, Garrett Fitzgerald, A. Apollonio, F Balsano, A Basellini, L. Candelise, M. Catalano, N. Ciavarella, Giovańni Ciuffetti, S Coccheri, M. Cortellaro, G Corvi, Vincenzo Coto, Giovanni Davı̀, R. DeCaterina, T. DiPerri, C. Fieschi, Ronald C. Gentile, L Gregoratti, Paolo Gresele, M Lavezzari, A Libretti, B Magnani, Gabriele Nenci, G Pagano, Carlo Patrono, L Pedrini, Massimo Pini, Paolo Prandoni, Fabiana Romeo, F Rovelli, G Rudelli, Giovanni Ruvolo, G P Signorini, Gianni Tognoni, Francesco Violi, Tomonari Fujimori, Manabu Kageyama, T Katsumura, Susumu Kitamura, Kenji Maeda, Atsushi Suzuki, Hideo Tohgi, Shinichiro Uchiyama, Hirofumi Utsumi, A.M. González García, Ale Algra, Denottolander Gjh., Kupper Ajf., J Vangijn, H. Hart, L. Jaap Kappelle, P. J. Koudstaal, T Lemmens, J. Lodder, Merel M. Pannebakker, Patrick W. Serruys, A Vandenbelt, J Vandermeer, A B Vandervijgh, Verheugt Fwa., G Veth, Jeremy Dale, Karl-Arne Johannessen, Erik Thaulow, P Popescu, Nyulas Tiberiu, Aznar Jrd., Enric Esmatjes, Pere Guiteras, José Luis Flordelís Lasierra, P Lopeztrigo, A Oriol, Léo Pomar, Evangelista Rocha, F D Sanchez, J. Sancho-Rieger, Gema Sanz, Ulf Berglund, Christian Blomstrand, Merike Boberg, M Britton, Carl‐Eric Elwin, C. Helmers, Johan Holm, Lars Janzon, Steen Juul‐Möller, H. Mulec, Jan-Edwin Olsson, Stig Persson, Gundars Rasmanis, Alan Rosen, Karin Samuelsson, Julius Soreff, N.G. Wahlgren, Lars Wallentin, Heiner Baur, M. Bokslag, A Bollinger, Bernhard Meier, M Pfisterer, Chitr Sitthi‐Amorn, Elise Acheson, P N Appleby, A. W. Asscher, A Aukland, Colin Baigent, S Bala, A H Barnett, P Bell, S Bews, Born Gvr., J. P. Branagan, N. Brooks, M J Brown, N L Browse, Rudy Capildeo, M. H. B. Carmalt, A E Carter, Ian Chalmers, Millie Clarke, R J Clarke, Clyne Cac., Rory Collins, Cooke, Graham Coutts, D.H. Cove, P. S. Crowther, William Cuthbertson, D Debono, Clark R. Dickerson, James Dickinson, R. Doll, J A Dormandy, DW Dunbabin, S Ell, P Elphinstone, P C Elwood, Veronica Englishby, Barbara Farrell, Carolyn E. FISKERSTRAND, Marcus Flather, Thomas A. Foley, Tatum E. Foulds, Kim Fox, Peter Franks, Hazel Fraser, T. Gardecki, Magdalena Gaweł, A.E. Gent, AH Gershlick, Jon Godwin, Mariano Goldman, C Gray, Denis Pereira Gray, Richard Gray, Helen HG Handoll, Graeme J. Hankey, Harrison Mjg., Neil Henderson, Stan Heptinstall, Stephen F. Hobbiger, E. Wilson Jones, Jones Nag., Stefan Jost, D G Julian, Joanne Kellett, R C Kester, G.D.O. Lowe, Justin MacKenzie, Charles McCollum, Gillian Mead, Tomw. Meade, David Mendelow, James C. Miller, G MORRIS, Chris Nichol, M I Noble, O'Brien O'Brien, Michaël Ogier, Sarah Parish, Monica Parry, Richard Peto, Jason Powell, Paolo Pozzilli, Nawab Qizilbash, Atikur Rahman, S M Rajah, Duncan Richards, Suzanne H Richards, Robert C. Ripley, V.C. Roberts, F. Clifford Rose, Russell Rwr, P. Rubin, C V Ruckley, Peter Sandercock, Shaw Mdm., Krista M Shaw, Joseph H. Shelley, J Slattery, Peter Sleight, Simon Smith, P. Stewart-Long, P M Sweetnam, Tansey Mjb., H Tindall, J H Turney, H. M. Tyler, N C Varey, M P Vessey, M G Walker, Marion A. Walker, Charles Warlow, Robert G. Wilcox, H. Willems, Edith Wood, E Wynjones, Hadie Adams, Bruce Barton, Robert F. Bedford, Benjamin L. Bick, S Bingham, B G Brown, T. N. Bryant, Julie E. Buring, Catherine F. Cabot, Paul L. Canner, J. H. Chesebro, O D Chrisman, G Clagett, John A. Colwell, Mark L. Dyken, D J Ellis, William S. Fields, C Furberg, Valentı́n Fuster, Steven Goldman, Jeffrey R. Granett, Ryanne Green, D Green, Rebecca Hardy, L A Harker, W.H. Harris, Robert G. Hart, William K. Hass, C H Hennekens, Deborah Hill, Megan Hume, M C Igloe, Grace L. Johnson, S Jonas, Genell L. Knatterud, Till Köhler, Nicholas Lembo, David A. Lewis, E Lockhart, Philip W. Majerus, Mcenany, R. McKenna, Jawahar L. Mehta, Jochen Meyer, Basil A. Molony, Thomas Moritz, D. M. Nicoloff, G Nycz, Hirotsugu Ono, George A. Pantely, Steve Phillips, Paul M. Ridker, James T. Robertson, Robert M. Rothbart, Salzman Ew, Richard D. Sautter, Robert C. Schlant, James A. Schoenberger, M V Sengekontacket, Gautam Sharma, Peter Steele, K P Steinnagel, Jon Stratton, Joshua Sullivan, Gerald C. Timmis, James F. Toole, Walker, Steven M. Weisman, Christopher W. White, M Wirecki, Duane G. Wombolt, Richard C.K. Wong, Salim Yusuf, Karen Zadina, David M. Zucker
Language: English
Subfield: Cardiology and Cardiovascular Medicine
Field: Medicine
Domain: Health Sciences
Open Access status: green
OpenAlex ID: W4239471829