TIMI grade 3 flow and reocclusion after intravenous thrombolytic therapy: A pooled analysis N. Alejandro Barbagelata, MD, a Christopher B. Granger, MD, b Ernesto Oqueli, MD, a Luis D. Sufirez, MD, a Miguel Borruel, MD, a Eric J. Topol, MD, c and Robert M. Califf, MD b Buenos Aires, Argentina, Durham, N.C., and Cleveland, Ohio Early and sustained flow of grade 3 according to Thrombol- ysis in Myocardial Infarction (TIMI) criteria and reocclusion rates are the key measures that define the physiologic effi- cacy of thrombolytic agents in the treatment of acute myo- cardial infarction. We performed a systematic overview of angiographic studies after intravenous thrombolysis with accelerated and standard-dose tissue-plasminogen activa- tor (TPA), anisoylated plasminogen streptokinase activator complex (APSAC), and streptokinase. There were 5475 an- giographic observations from 15 studies for TIMI flow anal- ysis and 3147 angiographic observations from 27 studies for reocclusion. At 60 and 90 minutes, the rates of TIM! grade 3 flow were 57.1% and 63.2%, respectively, with accelerated TPA, 39.5% and 50.2% with standard-dose TPA, 40.2% and 50.1% with APSAC, and 31.5% at 90 minutes with streptoki- nase. Overall reocclusion with standard-dose TPA was 11.8% versus 6.0% for accelerated TPA, 4.2% for streptoki- nase, and 3.0% for APSAC. Although the incidence of TIMI grade 3 flow increased over time with all thrombolytic reg- imens, decreased patency was observed at 180 minutes with accelerated TPA. Still, accelerated TPA is the most effective agent to establish early (90-minute) TIMI grade 3 flow. (Am Heart J 1997;133:273-82.) Early reperfusion of ischemic myocardium is the primary aim of intervention in patients who have acute myocardial infarction and ST-segment eleva- tion. The measured beneficial effects of this strategy provide empirical evidence of a time-sensitive mech- anism of reperfusion. The ability of an agent to maintain or even increase infarct-artery patency over time and prevent reocclusion after initial reper- fusion also may support the involvement of a time- insensitive mechanism. Indeed, many studies have found that earlier reperfusion and patency of the in- From athe Fundaci6n Favaloro, Buenos Aires; bthe Division of Cardiology, Department of Medicine, Duke University Medical Center, Durham; and %he Cleveland Clinic Foundation. Received for publication April 10, 1996; accepted Aug. 8, 1996. Reprint requests: N. Alejandro Barbagelata, MD, Solis 453, 1078 Buenos Aires, Argentina. Copyright © 1997 by Mosby-Year Book, Inc. 0002-8703/97/$5.00 + 0 4/1//8091 farct-related artery correlate with better subsequent outcomes. 1-5 Thrombolysis in Myocardial Infarction (TIMI) flow grades have become the standard measure of perfusion. 6 In most reperfusion studies, patent ar- teries have been defined as those with TIMI grade 2 or 3 flow, under the assumption that both grades are associated with similar clinical outcomes. Re- cently, however, separate analyses of TIMI grades 2 and 3 have become standard because of evi- dence of different outcomes as a function of TIMI grade 2 versus 3 flow, including differences in ven- tricular function measures, survival, and clinical events.5, %11 The time to achieve TIMI grade 3 flow also appears to have a relation with outcome: the earlier that TIMI grade 3 flow is achieved, the better the out- come. 5 Reocclusion of the artery--with silent or recurrent ischemia--and reinfarction are predictive of in-hospital and long-term mortality. 12-14Ohman et al. 12 have shown that in-hospital reocclusion is pre- dictive of recurrent events. Conversely, an open ar- tery at discharge predicts better outcome at 1-year follow-up. 11 Improvement in late patency with time, whether a spontaneous improvement or the result of intervention, also may have a role in long-term sur- vival through a time-independent mechanism. 15-2° To obtain more reliable estimates of patterns of TIMI grade 3 flow and reocclusion rates for several throm- bolytic strategies, we performed a systematic over- view of angiographic studies after intravenous thrombolytic therapy. METHODS Studies of intravenous thrombolytic therapy that also included acute and follow-up angiography were identified by a computer-aided search (MEDLINE), a review of ref- erence lists from angiographic study reports and related review articles, and a review of abstracts from the Amer- ican Heart Association and American College of Cardiol- ogy meetings from 1988 to 1994. Studies that met the fol- 273