(0 the TIM1 Data Coordinating Center on August 8, 1989 and therefore represent an update of the data previously published (1,2).

Transcription

1 JACC Vol. 15. No. 5 April I : , FACC, GENEJLL Boston, Massachusetts The Thrombolysis in ase I1 focused on the of patients with acute myocardial infarction after tbrombolytic treatment with intravenous recombinant tissue-type plasminogen activator (r&pa) and was designed to determine which of three alternative post-thrombolytic treatment strategies was preferable: 1) an immediate invasive strategy, in which the patient was taken directly to the catheterization laboratory for coronary arteriography and, if feasible, percutaneous transluminal angioplasty during infusion of &PA; 2) a delayed invasive strategy, in which routine coronary angiography was performed between 18 and 48 h after &PA therapy; and 3) a conservative strategy, in which coronary arteriography and, if indicated, angioplasty, were carried out only if the patient developed spontaneous or exerciseprovoked myocardial ischemia. For patients assigned to one of the two invasive strategy groups, if coronary angiog~phy disclosed significant (MI%) stenosis of the infarct-related artery, revascularization was to be attempted (using coronary angioplasty if technically possible) according to protocol-specified anatomic and clinical criteria (1,2). Patient entry began on April II, 1986 and ended on June 30, 1988 with enrollment of 3,534 patients. Trial results were presented for the first time in November 1988 and described in two publications (I,2). The constraint of available space for these first two reports did not permit full discussion of the concepts underlying the design of the trial and the interpretation of the results. Additional analyses of the results have now been performed (3-7). The purpose of this editorial is to provide additional information and perspectives on TI *Editorials published in Journal of the American College of Cardiology refkct the views of the authors and do not necessarily represent the views of JACC or the American College of Cardiology. From the Department of Medicine, Harvard Medical School and Brigham and Women s Hospital, Boston. Massachusetts. Address Eugene Braunwald. MD, Department of Medicine, Brigham and Women s Hospital, 75 Francis Street. Boston. Massachusens Ql990 by the American College of Cardiology was attempted. The remaiu~ng 39.5% (n = 593) of patients who underwent catbeteriza~iou in of the ocol did not have angioplasty performe bad < stenosis of the infarct-related artery, 12.2% had total occlusion with no ongoing manifestations of ischemia 13.1% d complex coronary anatomy that was conside obebr r managed by bypass surgery or medical therapy. Th e exclusions from attempted coronary angioplasty were deemed appropriate in light of current (24.3%) of these 593 patients required coronary artery byry within 21 days. ive versus e~u~~ative s&a y. Patients assigned to the delayed invasive strategy described were compared with 1,658 patients assigned to a conservative strategy, in which cardiac cathete~zation was reserved for the 587 patients (35.4%) who had either spontaneous myocardial ischemia within 21 days of 13.5% of patients in this arm of the Trial underwent coronary angioplasty, 7.6% underwent bypass surgery and 1.1% un- *The numbers presented in this editorial reflect the information available (0 the TIM1 Data Coordinating Center on August 8, 1989 and therefore represent an update of the data previously published (1,2) /90/$3.50

2 JACC Vol. 15. No. 5 April 19!JO: coronary a~~~op~asty ia the invasive strategy group when there was no evidence of criti anatomy was unsuitable is a cl1 s with every clinical trial, the results are

3 1190 BAiM ET AL. EDITORIAL 3Af.X Vol. IS. No. 5 April 1 :~~88-92 most applicable to patients similar to those entered into the trial. Of great interest are ongoing trials involving patients >76 years old, patients who present with ischemic chest pain and ST segment depression and patient after the onset of symptoms. However, apply in full to the substantial number ty criteria used to select the actual partici- II Trial. Thus far, analyses of many patient subgroups have failed to identify any in whom the invasive strategy was superior to the conservative one. with intravenous The results of any trial of the operators. In 1986, when the criteria for operator certification were ed on then current recommendations for the performance of angiopla e results of the patients) a primary success rate tion rate c7%, an emergency mortality rate <2%. Operators in t included a more demanding immediate catheterization and oplasty arm) were required to have performed more than angioplasty procedures, at least 29 of which were in patients with total occlusion. These were minimal requ ments; many operators had much greater ex~e~e~ce. operators met these requirements at the and developed substantially greater ex gery. However, the net benefit of anatomically more complex situations is unclear larly given the unfavorable effects of a more application of angioplasty in the trial carried out by the kropean Cooperative Study Group (10). It is unlikely that requiring greater operator experience would have affected the outcome of the trial substantially by ~rn~rov~~g angioplasty results. The high ment with a~gio~lasty, t gency surgery and lo related mortality in the sive arm of the study are among the bes results of coronary an sty in a group of early tion patients. Finally, enced or expert angioplasty operators are not available to treat most patients with acute myocardial infarction. amined only three well define whose total occlusio

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5 1192 BAIM ET AL. EDITORIAL JACC Vol. IS. No. 5 April f :118S-92, aspirin may be of incremental value to the fibrinolytic actions of tbrombol gents in the treatment of acute myocardial infarction. clinical trials have differed markedly in terms of the time, dose and route of aspirin administration. At its onset, T II included an immediate oral dose (80 mg) of aspirin at time the 150 mg rt-pa and heparin infusions were initiated. With the recognition of a higher than expected incidence of central nervous system bleeding events, the r&pa dose was reduced (150 to KM mg), and the initiation of aspirin therapy was delayed h (1). Thus, patients in t invasive arm I IIA (and a very small per delayed invasive arms) underwent coronar without prior aspirin therapy, a situation that m increase the incidence of postangioplasty ab mediate aspirin thera compari strategie would not be anticipated to have any main comparison of the delayed invasive strategy group with the conservative strategy group, because virtually all patients received aspirin before delayed angioplasty. Given the many thrombolytic agents and the ways in which they CLEI be combined with revascularization, the treatment of acute myoc tion has been the subject of active study and lively debate, which are likely to continue for some time. Several studies, including TM IIA (2,3,10,22), hav diate catheterization and angioplasty and have a greater c invasive strategy, but suggested that an even more conservative strategy of reserving catheterization and coronary angioplasty after thrombolytic therapy for patients with recurrent spontaneous OP exercise-induced ischemia may be the most desirable approach for the majority of patients similar to those entered into these trials. ces 1. The TIMI Study Group. Comparison of invasive and conservative strategies after treatment with intravenous tissue plasminogen activator. N Engl J Med 1989;320: Tbe TIM1 Research Group. immediate vs. delayed catheterization and angioplasty following thmmbolytic therapy for acute myocardial infarction. JAMA M&260: Rogers WJ, Bairn DS. Gore JM, et al. Comparison of immediate invasive, delayed invasive, and conservative strategies following tissue plasminogen activator: results of the Thrombolysis In Myocardial Infarction (TIMI) Phase II-A Trial. Circulation (in press). 4. Williams DD, Braunwald E, ~nat~e~d 6, et Myocardial Infarction ~~~~~ Trial: outcome randomized to either invasive or conservative management (abstr). Circulation 1989;8O(suppl11): Feit F, Mueller HS, Ross R omnary angiog~~by an plasty in the conservative arm o I1B: a comparison of y and satellite hospitals (abstr). C n 1989$O(suppl II):iM 6. Garrahy PJ, Henxlova MJ. Forman S, Rogers WJ. Has throm~lytic therapy improved su. from cardiogenic shock?: Tb Myocardiai Infarction I) results lab&). Circulation 11): Rogers WJ, Babb JD, Bairn DS, et al. Is pre-discharge coronary arterirction treated wilb nohara T, et al. Snrvival ergency coronary angiop dial infarction. J Am Coil Cardiol 1988;11: immediate percutaneous transluminal angioplasty. 16. de o DP. Pocock SJ, for the SW1 tnves~i~tor s Group. The SW study of intervention versus conservative management after antistreplase thmmbolysis (abstrl. Circulation 1989;8O(suppl11): Califf RM, Topol, George BS. et al. Characteristics and outcome of patients in whom reperfusion with intravenous tissue-type plasminogen activator fails: results of the Thmmbolysis and Angioplast y in Myocardial Infarction (TAMI) I trial. Circulation 198&71: I) Trial. Phase 1. A comparisoc n activator and intravenous sire ings tbmugh hospital discharge. Circulation l~7;7~~ Neuhaus K-L, Feuerer W. Jeep-Tebbe S, Niederer W, Vogl A, Tebbe W. Improved thrombolysis with a modified dose regimen of recombinant plasminogen activator. J Am Co11 Cardiol 1989;14: trolled clinical trial. Lancet Cardiol 1988;61: Effect of intravenons APSAC on ality : preliminary report of a plac con- binant single~b~n urokinasemyocardiai infarction. Am J O Keefe Jr, Rutherford BD, onahay DR. et al. Early and late results 0 ronary angioplasty w t antecedent thmmbolytic therapy for acute myocardial infarction. Am J Cardiol 1989,61: DeWood M. Spores J, Berg R, et al. Acute myocardial infarction: a decade of experience with surgical reperfusion in 701 patients. Circulation 1983;till8-26. Topol BJ, CalilT RM. George BS. et al. Can emergency caronary angiography and rescue angioplasty improve infarct vessel patency after 8-S lrial preliminary results (ah&r). Circulation 1989;8o(suppl 11): Schwartz L, Bourassa MG, Lesperance J, et al. Aspirin and dipyridamole in Ihe prevention of restenosis after percutaneous transluminal coronary angioplasty. N Engl J Med 1988;318: Top01 EJ, Calii RM. George BS, et al. A randomize versus delayed elective angioplasty after intravenous tissue plasminogen activator in acub myocardial infarction. N Engl J Med 1987;317:581-8.