ISIS-2: 10 year survival among patients with suspected acute myocardial infarction in randomised comparison of intravenous streptokinase, oral aspirin, both, or neither

BMJ 1998;316:1337-1343 ( 2 May )

Papers

ISIS-2: 10 year survival among patients with suspected acute myocardial infarction in randomised comparison of intravenous streptokinase, oral aspirin, both, or neither

Colin Baigent, Medical Research Council scientist, Rory Collins, British Heart Foundation professor of medicine and epidemiology, Paul Appleby, research officer, Sarah Parish, Medical Research Council scientist, Peter Sleight, professor emeritus of cardiology, Richard Peto, professor of medical statistics and epidemiology,

Clinical Trial Service Unit and Epidemiological Studies Unit, Nuffield Department of Clinical Medicine, Radcliffe Infirmary, Oxford OX2 6HE

Correspondence to: Dr Baigent colin.baigent{at}ctsu.ox.ac.uk

Objective: To assess effects of intravenous streptokinase, one month of oral aspirin, or both, on long term survivalafter suspected acute myocardial infarction.
Design: Randomised, "2×2 factorial," placebo controlled trial.
Setting: 417 hospitals in 16 countries.
Subjects: 17 187 patients with suspected acute myocardial infarction randomised between March 1985 and December 1987.Follow up of vital status complete to at least 1 January 1990for 95% of all patients and to mid-1997 for the 6213 patientsin United Kingdom.
Interventions: Intravenous streptokinase (1.5 MU in 1 hour) and oral aspirin (162 mg daily for 1 month) versus matchingplacebos.
Main outcome measures: Mortality from all causes during up to 10 years' follow up, with subgroup analyses based on4 year follow up.
Results: After randomisation, 1841 deaths were recorded in days 0-35, 991 from day 36 to end of year 1, 1478 in years2-4, and 1230 in years 5-10. Allocation to streptokinase was associatedwith 29 (95% confidence interval 20 to 38) fewer deaths per 1000patients during days 0-35. This early benefit persisted (deathrate ratio 0.98 (0.92 to 1.04) for additional deaths between day36 and end of year 10), so that there were 28 (14 to 42) and 23(2 to 44) fewer deaths per 1000 patients treated with streptokinaseafter 4 years and 10 years respectively. There was no evidencethat absolute survival benefit increased with prolonged followup among any category of patient, including those presenting earlyafter symptoms started or with anterior ST elevation. Nor didthe early benefits seem to be lost in any category (includingthose aged over 70). Allocation to one month of aspirin was associatedwith 26 (16 to 35) fewer deaths per 1000 during first 35 days,with little further benefit or loss during subsequent years (deathrate ratio 0.99 (0.93 to 1.06) between day 36 and end of year10). The early benefit obtained with combination of streptokinaseand one month of aspirin also seemed to persist long term.
Conclusions: The early survival advantages produced by fibrinolytic therapy and one month of aspirin started in acutemyocardial infarction seem to be maintained for at least 10 years.

Key messages

Large randomised trials have shown that the survival benefits of intravenous fibrinolytic therapy for patients with acute myocardial infarction persist for at least one year, but there is relatively little information about longer term effects
By contrast, this report from the ISIS-2 trial of intravenous streptokinase and of one month of oral aspirin includes nearly 4000 deaths between the start of year 2 and the end of year 10
The early survival benefits of fibrinolytic therapy persist for at least 10 years after treatment and do not seem to increase or decrease with prolonged follow up in any category of patients, including elderly subjects
The survival benefits of short term aspirin treatment in acute myocardial infarction also persist long term and are additional to those of fibrinolytic therapy, and other studies show that these benefits can be increased by continuing aspirin treatment for some years after myocardial infarction

© BMJ 1998

CiteULike

Complore

Connotea

Del.icio.us Add to Digg

Digg

StumbleUpon Add to Technorati

Technorati What's this?

Relevant Article

Survival benefits of fibrinolysis and early aspirin in acute myocardial infarction are sustained
BMJ 1998 316: 0. [Full Text]

This article has been cited by other articles:

Kirchhof, P., Bax, J., Blomstrom-Lundquist, C., Calkins, H., Camm, A. J., Cappato, R., Cosio, F., Crijns, H., Diener, H.-C., Goette, A., Israel, C. W., Kuck, K.-H., Lip, G. Y.H., Nattel, S., Page, R. L., Ravens, U., Schotten, U., Steinbeck, G., Vardas, P., Waldo, A., Wegscheider, K., Willems, S., Breithardt, G. (2009). Early and comprehensive management of atrial fibrillation: Proceedings from the 2nd AFNET/EHRA consensus conference on atrial fibrillation entitled 'research perspectives in atrial fibrillation'. Europace 11: 860-885 [Full text]
Levy, W. C., Mozaffarian, D., Linker, D. T., Kenyon, K. W., Cleland, J. G.F., Komajda, M., Remme, W. J., Torp-Pedersen, C., Metra, M., Poole-Wilson, P. A., on behalf of the COMET Investigators, (2009). Years-needed-to-treat to add 1 year of life: a new metric to estimate treatment effects in randomized trials. Eur J Heart Fail 11: 256-263 [Abstract] [Full text]
Zannad, F., Bousquet, P., Monassier, L. (2009). CHAPTER 11 Clinical Pharmacology of Cardiovascular Drugs. ESC Textbook of Cardiovascular Medicine 2: med-9780199566990-chapter-med-9780199566990-chapter [Abstract] [Full text]
Goodman, S. G., Menon, V., Cannon, C. P., Steg, G., Ohman, E. M., Harrington, R. A. (2008). Acute ST-Segment Elevation Myocardial Infarction: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th Edition). Chest 133: 708S-775S [Abstract] [Full text]
Vijayaraghavan, R., Yan, A. T., Tan, M., Fitchett, D. H., Georgescu, A. A., Hassan, Q., Langer, A., Goodman, S. G., for the Canadian Acute Coronary Syndromes Registry, (2008). Local hospital vs. core-laboratory interpretation of the admission electrocardiogram in acute coronary syndromes: increased mortality in patients with unrecognized ST-elevation myocardial infarction. Eur Heart J 29: 31-37 [Abstract] [Full text]
Singh, M., White, J., Hasdai, D., Hodgson, P. K., Berger, P. B., Topol, E. J., Califf, R. M., Holmes, D. R. Jr (2007). Long-Term Outcome and its Predictors Among Patients With ST-Segment Elevation Myocardial Infarction Complicated by Shock: Insights From the GUSTO-I Trial. J Am Coll Cardiol 50: 1752-1758 [Abstract] [Full text]
Anderson, J. L., Adams, C. D., Antman, E. M., Bridges, C. R., Califf, R. M., Casey, D. E. Jr, Chavey, W. E. II, Fesmire, F. M., Hochman, J. S., Levin, T. N., Lincoff, A. M., Peterson, E. D., Theroux, P., Wenger, N. K., Wright, R. S., Smith, S. C. Jr, Jacobs, A. K., Adams, C. D., Anderson, J. L., Antman, E. M., Halperin, J. L., Hunt, S. A., Krumholz, H. M., Kushner, F. G., Lytle, B. W., Nishimura, R., Ornato, J. P., Page, R. L., Riegel, B. (2007). ACC/AHA 2007 Guidelines for the Management of Patients With Unstable Angina/Non-ST-Elevation Myocardial Infarction: A Report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Writing Committee to Revise the 2002 Guidelines for the Management of Patients With Unstable Angina/Non-ST-Elevation Myocardial Infarction) Developed in Collaboration with the American College of Emergency Physicians, the Society for Cardiovascular Angiography and Interventions, and the Society of Thoracic Surgeons Endorsed by the American Association of Cardiovascular and Pulmonary Rehabilitation and the Society for Academic Emergency Medicine. J Am Coll Cardiol 50: e1-e157 [Full text]
Sullivan, J. L (2007). The Big Idea: the coxib crisis Iron, aspirin and heart disease risk revisited. JRSM 100: 346-349 [Full text]
Mangano, D. T., Miao, Y., Vuylsteke, A., Tudor, I. C., Juneja, R., Filipescu, D., Hoeft, A., Fontes, M. L., Hillel, Z., Ott, E., Titov, T., Dietzel, C., Levin, J., for the Investigators of The Multicenter Study of, (2007). Mortality Associated With Aprotinin During 5 Years Following Coronary Artery Bypass Graft Surgery. JAMA 297: 471-479 [Abstract] [Full text]
Nieuwlaat, R., Capucci, A., Lip, G. Y.H., Olsson, S. B., Prins, M. H., Nieman, F. H., Lopez-Sendon, J., Vardas, P. E., Aliot, E., Santini, M., Crijns, H. J.G.M., on behalf of the Euro Heart Survey Investigators, (2006). Antithrombotic treatment in real-life atrial fibrillation patients: a report from the Euro Heart Survey on Atrial Fibrillation. Eur Heart J 27: 3018-3026 [Abstract] [Full text]
Lip, G. Y. H., Karpha, M. (2006). Anticoagulant and Antiplatelet Therapy Use in Patients With Atrial Fibrillation Undergoing Percutaneous Coronary Intervention: The Need for Consensus and a Management Guideline. Chest 130: 1823-1827 [Abstract] [Full text]
Lip, G. Y.H. (2006). Aspirin for Prevention of Stroke in Atrial Fibrillation. Stroke 37: 1640-1640 [Full text]
Rodriguez, T, Malvezzi, M, Chatenoud, L, Bosetti, C, Levi, F, Negri, E, La Vecchia, C (2006). Trends in mortality from coronary heart and cerebrovascular diseases in the Americas: 1970-2000.. Heart 92: 453-460 [Abstract] [Full text]
Chase, D, Roderick, P, Cooper, K, Davies, R, Quinn, T, Raftery, J (2006). Using simulation to estimate the cost effectiveness of improving ambulance and thrombolysis response times after myocardial infarction. Emerg. Med. J. 23: 67-72 [Abstract] [Full text]
Vorchheimer, D. A., Becker, R. (2006). Platelets in Atherothrombosis. Mayo Clin Proc. 81: 59-68 [Abstract] [Full text]
van Domburg, R. T., Sonnenschein, K., Nieuwlaat, R., Kamp, O., Storm, C. J., Bax, J. J., Simoons, M. L. (2005). Sustained Benefit 20 Years After Reperfusion Therapy in Acute Myocardial Infarction. J Am Coll Cardiol 46: 15-20 [Abstract] [Full text]
Juhlin, T., Bjorkman, S., Gunnarsson, B., Fyge, A., Roth, B., Hoglund, P. (2004). Acute administration of diclofenac, but possibly not long term low dose aspirin, causes detrimental renal effects in heart failure patients treated with ACE-inhibitors. Eur J Heart Fail 6: 909-916 [Abstract] [Full text]
Tran, H., Anand, S. S. (2004). Oral Antiplatelet Therapy in Cerebrovascular Disease, Coronary Artery Disease, and Peripheral Arterial Disease. JAMA 292: 1867-1874 [Abstract] [Full text]
Ndrepepa, G., Kastrati, A., Neumann, F.-J., Schmitt, C., Mehilli, J., Schomig, A. (2004). Five-year outcome of patients with acute myocardial infarction enrolled in a randomised trial assessing the value of abciximab during coronary artery stenting. Eur Heart J 25: 1635-1640 [Abstract] [Full text]
Menon, V., Harrington, R. A., Hochman, J. S., Cannon, C. P., Goodman, S. D., Wilcox, R. G., Schunemann, H. J., Ohman, E. M. (2004). Thrombolysis and Adjunctive Therapy in Acute Myocardial Infarction: The Seventh ACCP Conference on Antithrombotic and Thrombolytic Therapy. Chest 126: 549S-575S [Abstract] [Full text]
Channer, K. S (2004). Primary angioplasty should be first line treatment for acute myocardial infarction: AGAINST. BMJ 328: 1256-1257 [Full text]
Tunis, S. R., Stryer, D. B., Clancy, C. M. (2003). Practical Clinical Trials: Increasing the Value of Clinical Research for Decision Making in Clinical and Health Policy. JAMA 290: 1624-1632 [Abstract] [Full text]
Awad-Elkarim, A A, Bagger, J P, Albers, C J, Skinner, J S, Adams, P C, Hall, R J C (2003). A prospective study of long term prognosis in young myocardial infarction survivors: the prognostic value of angiography and exercise testing. Heart 89: 843-847 [Abstract] [Full text]
McAlister, F. A., Straus, S. E., Sackett, D. L., Altman, D. G. (2003). Analysis and Reporting of Factorial Trials: A Systematic Review. JAMA 289: 2545-2553 [Abstract] [Full text]
Savage, M. W, Channer, K. S (2002). Improving the management of acute myocardial infarction. BMJ 325: 1185-1186 [Full text]
Tyden, P, Hansen, O, Engstrom, G, Hedblad, B, Janzon, L (2002). Myocardial infarction in an urban population: worse long term prognosis for patients from less affluent residential areas. J. Epidemiol. Community Health 56: 785-790 [Abstract] [Full text]
Baker, J W, Mitchell, S J, Dixon, A R (2002). Early diagnosis of colonic carcinoma: a haemorrhagic complication after the use of tissue plasminogen activator. Postgrad. Med. J. 78: 429-429 [Abstract] [Full text]
Cleland, J. G F (2002). Chronic aspirin is effective---if data are massaged sufficiently. BMJ 324: 295-295 [Full text]
Baigent, C., Collins, R., Peto, R. (2002). Article makes simple errors and could cause unnecessary deaths. BMJ 324: 167-167 [Full text]
Mukamal, K. J., Nesto, R. W., Cohen, M. C., Muller, J. E., Maclure, M., Sherwood, J. B., Mittleman, M. A. (2001). Impact of Diabetes on Long-Term Survival After Acute Myocardial Infarction: Comparability of risk with prior myocardial infarction. Diabetes Care 24: 1422-1427 [Abstract] [Full text]
Channer, K S, Pugh, P J (2001). Interfering with healing: the benefits of intervention during acute myocardial infarction. Heart 85: 620-622 [Full text]
Malik, I S, Bhatia, V K, Kooner, J S (2001). Cost effectiveness of ramipril treatment for cardiovascular risk reduction. Heart 85: 539-543 [Abstract] [Full text]
Thompson, C. A., Jabbour, S., Goldberg, R. J., McClean, R. Y. S., Bilchik, B. Z., Blatt, C. M., Ravid, S., Graboys, T. B. (2000). Exercise performance-based outcomes of medically treated patients with coronary artery disease and profound ST segment depression. J Am Coll Cardiol 36: 2140-2145 [Abstract] [Full text]
Topol, E. J., Ohman, E. M., Armstrong, P. W., Wilcox, R., Skene, A. M., Aylward, P., Simes, J., Dalby, A., Betriu, A., Bode, C., White, H. D., Hochman, J. S., Emanuelson, H., Vahanian, A., Sapp, S., Stebbins, A., Moliterno, D. J., Califf, R. M. (2000). Survival Outcomes 1 Year After Reperfusion Therapy With Either Alteplase or Reteplase for Acute Myocardial Infarction : Results From the Global Utilization of Streptokinase and t-PA for Occluded Coronary Arteries (GUSTO) III Trial. Circulation 102: 1761-1765 [Abstract] [Full text]
Braunwald, E., Antman, E. M., Beasley, J. W., Califf, R. M., Cheitlin, M. D., Hochman, J. S., Jones, R. H., Kereiakes, D., Kupersmith, J., Levin, T. N., Pepine, C. J., Schaeffer, J. W., Smith, E. E. III, Steward, D. E., Theroux, P., Gibbons, R. J., Alpert, J. S., Eagle, K. A., Faxon, D. P., Fuster, V., Gardner, T. J., Gregoratos, G., Russell, R. O., Smith, S. C. Jr (2000). ACC/AHA guidelines for the management of patients with unstable angina and non-st-segment elevation myocardial infarction: A report of the american college of cardiology/ american heart association task force on practice guidelines (committee on the management of patients with unstable angina). J Am Coll Cardiol 36: 970-1062 [Full text]
Swedberg, K. (2000). The future: cardiovascular medicine in 10 years. Heart 84: 48i-49 [Full text]
Berger, A. K., Radford, M. J., Wang, Y., Krumholz, H. M. (2000). Thrombolytic therapy in older patients. J Am Coll Cardiol 36: 366-374 [Abstract] [Full text]
Kennedy, J. W. (2000). Thrombolytic therapy in acute myocardial infarction. J Am Coll Cardiol 35: 25B-28B
Awtry, E. H., Loscalzo, J. (2000). Aspirin. Circulation 101: 1206-1218 [Full text]
(2000). Tackling myocardial infarction. DTB 38: 17-22 [Abstract] [Full text]
BOERSMA, E (1999). Acute myocardial infarction: bring the treatment to the patient. Heart 82: 404-404 [Full text]
French, J. K., Hyde, T. A., Patel, H., Amos, D. J., McLaughlin, S. C., Webber, B. J., White, H. D. (1999). Survival 12 years after randomization to streptokinase: the influence of thrombolysis in myocardial infarction flow at three to four weeks. J Am Coll Cardiol 34: 62-69 [Abstract] [Full text]
Rawles, J., Lundergan, C. F., Ross, A. M. (1998). Extended Mortality Benefit of Early Postinfarction Reperfusion • Response. Circulation 98 : 2932-2935 [Full text]
Califf, R. M. (1998). Ten Years of Benefit From a One-Hour Intervention. Circulation 98: 2649-2651 [Full text]
Franzosi, M. G., Santoro, E., De Vita, C., Geraci, E., Lotto, A., Maggioni, A. P., Mauri, F., Rovelli, F., Santoro, L., Tavazzi, L., Tognoni, G. (1998). Ten-Year Follow-Up of the First Megatrial Testing Thrombolytic Therapy in Patients With Acute Myocardial Infarction : Results of the Gruppo Italiano per lo Studio della Sopravvivenza nell'Infarto-1 Study. Circulation 98: 2659-2665 [Abstract] [Full text]
(1998). The Lasting Benefits of Thrombolysis in MI. JWatch General 1998: 2-2 [Full text]