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44A JAW ““I 12. No h Dccemhcr iYXX:44&5lA

Reperfusion Therapy in Inferior

ERIC R. BATES, MD. FACC Am Arbor, Mkltipor

This review summarizes the multicenter trial results of reperfusion therapy for treatment of inferior myocardial infarction, Therapy with intracoronzy or intravenous recombinant tissue plasminogen activator (rt- PA) produced higher patency rates than did intravenous streptokinase. Reocchtsion was more common when the right coronary artery was the infarct-related artery, irre- spective of treatment strategy. LeR ventricular ejection fraction was improved compared with that in control patients, especially when the time from symptom onset was brief or when patency rates were high. Enzymatic infarct size was redmod in treated patients. A trend toward mortality reduction in treated patients was found in four studies and was statistically significant in the Second Inter- national Study of Infarct Survival (ISIS-2) trial. Precordlal ST segment depression in inferior myocar-

The use of thrombolytic therapy in patients with inferior Multicenter Tiwumbolytic Trial Designs myocardial infarction has been a controversial subject. Eleven multicenter trials have publisheddata concerning Whereas it is generally acknowledged that patients with inferior myocardial infarction before March 1988.The trials anterior myocardial infarction benefit from thrombolytic can be groupedinto intracoronary streptokinase trials, intra- therapy, the utility of treating patients with inferior infarc- venous streptokinase trials and intravenous recombinant tion, in whom the clinical course tends io be relatively tissue plasminogenactivator (r&PA) trials (Table I). benign. has been more difficult for many clinicians to accept. Consequently, some investigators (I) have recommended Intracoronary streptokinnse trials. The Western Wash- that thrombolytic therapy be limitedto patientswith anterior ington lntracoronary Streptokinase (WWlCS) trial (2-7) myocardial infarction. carolled 134patients with inferior infarction amonga total of When examined in aggregate, however, a substantial 250 study patients in 14hospitals from July 1981to February amount of data from conlrolled randomized multicenter 1983. Patients admitted within 12 h of symptom onset trials supports the use of thrombolytic therapy in inferior underwent cardiac catheterization,and those randomized to infarction. The purpose of this report is to summarize the intracoronary streptokinase therapy received an average of results of those trials. When these data are analyzed in the 286,000U infused over 72 min. Mean time to randomization context of time to treatment,coronary patency and reocclu- was 4.6 h; only 22% of patients were randomized in <3 h. sion rates and ischemic burden, strong support for the Mechanical ( or bypass graft application of thrombolytic therapy in most patients with ) was accomplishedin 10% of patientswithin 30 days inferior infarction becomes apparent. and in 26% of patients by I year. All patients were treated with ,followed by warfarin. The Nerherktnds Inferrtniversiry friul (8-18) entered 287 From the Dwsion of Cnrdrology. Department of Internal Medicine, patientswith inferior myocardial infarction amonga total of Unwer~~ly of Mlchq,an. Ann Arbor. Micblgan. 533 study patients in five hospitalsfrom June 1981to March -for Eric R. Bates. MD, Division ofCardmlogy. Univer- sdy Hospital. 1500 East Medical Cenler Drive. 3910 ‘Taubman. Ann Arbor. 1985.Patients with symptoms ~4 h in duration were eligible Michigan 481139-0366. to undergo cardiac catheterization and an intracoronary

819118 by the Amerlcsn Collcgc of Cadmlogy 073.5.loY7/88/$3.50 JACC VOI. IL i-4” 6 BATES Dcccmhcr 1988 44A-(IA KL-PERI ,#il<)N IN INFERKIR MYrJCARDI,L INFARCTION

SK/n-PA Do*

Intracoronary SK WWICS (2-7) 7iHI IO 21x3 I4 XI I? 4.6 Netherland\ 6lXl I” 3/x5 5 573 4 13 o!-Inl lnlr.ivenous SK GISSI ,I%??) 2,R.l 1‘1 NH IX liwl 12 ISAM 123-25) l/X2 111 3/x9 1x I 741 6 ?!z !26! XIX4 1” Xillh 4 IF’, 4 30 WWIVS 127) Y/X1 10 7/X6 27 IhX 6 3.5 TIMI-I I%-301 xix4 lo 28s II II9 7 4.8 Inlraven”“> r&PA TIMI-I I?&30) 8W4 to .?M 13 II? 7 46 3 TAMI-I (31. 321 1215 l” lwl 4 1X6 6 2.9 6 10 X Hopkins 133) 12184 to 3/X7 3 13x 4 3.2 TIC0 (34) 5 105 25 1.9 Auslraba (35) 5186 lo XI87 5 I44 .I 3.3

GlSSl = Gmppo ltallano per lo Study” della Streptochmdv nell’lnfano Miwardico; !MI = mfenor myocardlai mhrclion: ISAM = Intravenous Streptokmace I” Acute Myocardlal Inhrct~on. NZ = New Zealand; PIS = pauents. r&PA = recombmant tw”r plasmmogen actwator: Rx = watment: SK = weptokmaw: TAM1 = Thrombalyrlc and Angmplssty in Myocardral Infdrcllon. TIC0 = Thrombolyrar I” Acule Coranrry Occlwon: TIM1 = Tbrombolyc~r m Myocardial Infarction: WWICS = Wertern Wa,hmgt”n Intracoronary Strept”k,nasse trial: WWIVS = Wesrem Washington intravenous Streptokmase trial.

streptokinase infusion of 250,000U over I h. Control pa- hospuals from March 1982to March 1985.Patients admitted tients did not undergo emergency cardiac catheterization. within 6 h of symptom onset and randomized to streptoki- Elective cardiac catheterization was performed in 76% of the nase received I.5 million U over I h. Half of the patients total patient group just before hospitaldischarge. Forty-four Yere treated within 3 h. Emergency cardiac catheterization percent of the treatment group were pretreated with 500.000 was not performed, but 53% underwent cardiac catheteriza- IJ of intravenous streptokinase and 17% underwent emer- tion 4 weeks later. Patients were treated with , gency angioplasty. Mean time to treatment was 3.3 h. heparin and an oral agent.Mechanical revas- Mechanical revascularization was performed in 15% of the cularization was undertaken in I I% of patientsby 7 months. control patientsand 3% of the treatment patientsby I year. The NW Zealand trial (26) enrolled 91 patients with Patientswere also treated with aspirin, heparin andan oral inferior infarction amonga total of I55 study patientswith a anticoagulantagent. first myocardial infarction in four hospitalsfrom August 1984 Intravenous streptokioaw trials. The Gruppo Italian0 per to August 1986.Patients admitted within 4 h and randomized lo Studio della Streptochinasi nell’lnfarto Miocardico to intravenous strep:okinase received I.5 million U over 30 (GISSI) trial (N-22) enrolled 4,013 patients with inferior min. Mean time to treatment was 3 h. Cardiac catheteriza- myocardial infarction amonga total of Il.806 study patients tion was performed3 weeks later. Patientswere also treated in 176 coronary care units from February 1984to June ,485. with aspirin, dipyridamole and heparin. Patientsadmitted within I2 h of symptom onset and random- The Western Washington Intravenous Streptokinase in ized to treatment received I.5 million U of intravenous Acrrte Myocardial Ittfarction trial (27) enrolled 234 patients streptokinase over 60 min. Half of the patients were treated with inferior infarction amonga total of 368 study patientsin within 3 h. Cardiac catheterization was not performed. Ten 27 hospitals from September 1983 to July 1986. Patients percent of the patients were older than 75 years and 50% randomizedwithin 6 h to streptokinase received 1.5million were older than 65 years. Only 20% received heparin and U over I h. Mean time to treatment was 3.5h. Streptokinase- 14% received aspirin. Fewer than 4% of patients underwent treated patientswere also treatedwith heparin and warfarin. mechanical revascularization, making the control group a Mechamcal revascularization was performed in 11% of pa- cohort of medically treated patients followed up for I year tients before hospital discharge. after acute myocardial infarction. Intravenous tissue plasminogen activator trials. The The Intravenotrs Streptokinase in Actrte Myocardial Iv- in Myocardial Infarction (TIMI) phase I trial firction (HAM) trial (23-25) entered 877 patients with (28-30)entered I I9 patientswith inferior infarction amonga inferior infarction amonga total of I.741 study patientsin 38 total of 232 study patients with occluded infarct-related 46A BATES ,ACC ““I. 12. NO. 6 REPERF”S,“N IN INFERIOR MYDCARDIAL INFARCTION Dccemher 19RR:44A-51A arteries in 13 hospitalsfrom August 1984to February 1985. Table2. Acute PatencyRates in Inferior and Anterior Patients were treated within 7 h and received either I.5 Myocardialinfarction millionU of imravenous streptokinase over I h or 80 mg of Patency (%) double chain rt-PA over 3 h. Mean time to treatment was 4.8 Time to NO. Rx(h) IMI AMI h. Patientswere also treatedwith aspirin, dipyridamole and - heparin. Mechanical revascularization was performed in lntracoronary SK WWICS (2) 134 4.6 -68 -68 24% of patients before hospitaldischarge. Nerherlands (13) 287 3.3 88 83 The Thrombolysis and Angioplasty in Myocardial Infarc- tntravenous SK rioa (TAM/) trial (31,32) enrolled 223 patients with inferior ISAM (25) 877 3 -34 -48 infarction amonga total of 386 study patientsin four hospi- TIMI-I (28) 57 4.8 35 28 iais fiOlX Deccmbc: .,.,>lo*< !o Cc!ober !9Rh All patients lnlravenous r&PA received 150mg of singlechain r&PA intravenously within 6 TIMI-I (28) 62 4.8 53 7: h of symptom onset. Mean time to treatment was 2.9 h. TAMI-I (37) 233 2.9 68 (91) 77 (%) Suitablepatients were randomized to immediateor delayed AM1 = anterior myocardial infarction: other abbreviations as in Table I. angioplasty. Patientswere also treated with aspirin, dipyri- Figures in parentheses represent palency ratesafter addition of immediate damoleand heparin. Mechanical revascularization was per- angioplasty to thrombolytic therapy. formed in 67% of patients before hospital discharge. Three smaller placebo-controlled trials evaluated the ef- fect of earlv treatment with r&PA on left ventricular function with inferior infarction versus 48% of those with anterior after acute myocardial infarction. The Hopkins trial (33) infarction. This was believed to imply a higher reperfusion randomized 80 patients with inferior myocardial infarction rate in patients with anterior infarction. With use of angio- and measuredejection fraction 10 days later. The Throm- graphic criteria, the TIMI-I trial (28) reported a 35% reper- bolysis in Acute Coronary Occlusion (TICO) trial (34) ran- fusion rate of occluded arteries in inferior infarction with domized 69 patients with inferior myocardial infarction and streptokinase. which improved to 53% with rt-PA. Corre- measuredejection fraction 21 days later. The National sponding results in anterior infarction were 28 and 71%. Foundation of Australia Coronary Thrombolysis Group (35) respectively. In the TAMI-I trial (31), in which time to randomized 84 patients with inferior myocardial infarction treatment was earlier and a high dose of single chain rt-PA and measuredejection fraction I week later in 61 patients. was used, the patency rate in inferior infarction was 68% after thrombolytic therapy and 91% after additionaltherapy Multicenter Trial Results in Inferior with immediate angioplasty compared with the results in anterior infarction in which patency raies were 77 and %%, Myocardial Infarction respectively (37). Thus, it appears that early intracoronary The factors that need to be considered when determining streptokinase and intravenous r&PA are significantly more the efficacy of a coronary repetfusion strategy include time effective than intravenous streptokinase in establishing re- to treatment, coronary patency, reocclusion, left ventricular perfusion in inferior myocardial infarction and that angio- function, infarct size and mortality rate. plasty can further increase reperfusion rates. The lower Coronary Patency(Table 2). Patency rates after throm- patency rates in inferior infarction with intravenous therapy bolytic therapy are presented in Table 2. lntracoronary may be due to larger volume in the right coronary streptokinase appears to be equally effective in recanalizing artery (30). Decreased branching (30). increased recruitment occluded coronary arteries independentof infarct location. of collateral circulation (6), increased tortuosity, lower re- Although the WWICS trial has not reported its patency rate sistance in the right ventricular perfusion bed and increased by infarct location. the overall 68% patency rate (2) is almost vagal tone are some of the explanations for lower blood flow identical to the 72% patency rates for both anterior infarction velocity in the infarct-related artery and the potential for and inferior infarction recorded in the lntracoronary Strep increased stasis and thrombosis. tokinase Registry of the Society for Cardiac Reocciusion. Coronary reocclusion after successful (36). for which time to treatment was similar. Earlier treat- thrombolysis frequently compromises the gains achieved by ment with intracoronary streptokinase in the Netherlands reperfusion in terms of myocardial salvage and potential trial (13) was associated with a patency rate of 88% for effect on infarct healing.A significant limiting factor in the inferior infarction and 83% for anterior infarction. long-term outcome of patients after inferior myocardial Patency rates, however, decrease with intravenous infarction is that reinfarction or reocclusion is more common thrombolytic therapy, particalarly with streptokinase, and than in anterior myocardial infarction irrespective of the seem to be lower in inferior than in anterior myocardial reperfusion strategy. The Netherlands trial (15) showed a infarction. In the ISAM study (25). creatine kinase (CK) MB 1% I year reinfarction rate after inferior infarction com- isoenzyme levels peaked in less than 9 h in 34% of patients pared with an 8% rate after anterior infarction (p = 0.008). Table 3. Left Ventricular EJCC~W Fr;~ctwn m Infcrtor Myocmlial Infarction De.,lh\ Ipi, LVEF I’;1

Time 10 rre.,led Control Trlrl n Rx Ihl PI\ PI\ p V.due Strcptokmw WWICS IX wkll3l IIX 46 52 49 I, II WWIVS II0 day\) 127) I?1 15 ii 5, 0 w Netheiland\ 00 day\) IlO) IX4 1 3 57 49 0 IWU,, NZ (3 wkl 1261 91 1 ,I M, 55 I, II5 CPA Hopkins II0 day51 11% HO 1? 59 $4 I, OS TIC0 I3 wkll34) SY i j g, C’> !! !!!7 Aurrralia II wk) ,351 61 13 h! 57 0 IO Infarct size. Enzymatically determined mtarct size was

LVEF = Ien ventricular e~emcn fracmn. &her dbbrwwm\ ,I* m mca\ured in two studies. The Netherlands trie! !:4). with Table I. high reperfuslon rates, demonstrated a 31% reduction in Infarct \ire (p = O.OiI7) in treated patients. The ISAM trial (25). with lower reperfusion rates. demonstrated a 14% reduction m Infarct size (p = 0.03) m treated patients. Reocclusion of the right coronary artery \eems to be the Mortality (Tables 4 and 5). The mortality rates associated major problem. The ISAM (24) trial reported a 20% reocclu- wi:b inferior myocardial infarction are lower than those qeen sion rate in the right coronary artery within 4 week\ of with anterior infarction. For a proportionately similar bene- streptokinase therapy versus % in the left anterior descend- ficlal effect of thrombolytic therapy on mortality rate to be ing coronary artery. The TAMI-I (37) trial found a 21% demonstrated. larger patient sample sizes will be required. A reocclusion rate in the right coronary artery I week after \tati\tically Imignificant trend in favor of mortality reduction r&PA compared with 12% in the left anterior descendmg in treated patients was found in four placebo-controlled artery and 5% in the left circumflex artery (p = 0.01). studies (2,4.13.15,19,21.24.25). but not in the Western Wash- Similarly, in the TAMI- trial with 1 h infusions of r&PA and ington mtravenuus trial (271 (Tables 4 and 5). The inadequate , the I week reocclusion rate was 67, i:: :bc left study size limited the statistical power of the two intracoro- anterior descending and 18% in the right coronary artery nary studies. whereas the intravenous streptokinase trials (unpublished data). Futurb treatment strategies ih?! de were limited by the low patency rates associated with that crease reocclusion rates would particularly improve the therapy. Moreover, a comparison of the mortality rates in results of acute intervention in inferior myocardial infarc- the control groups suggests that the patients enrolled in the tion. Western Washington trials had a much lower mortality risk Left ventricular function (Table 3). Preservation of left than was observed in the other trials. Other limitations in the ventricular function is largely dependent on the time to GISSI trial (19) include older patient age, symptom duration treatment and coronary patency rate. Data on left ventricu- up :o I2 h and absence of anticoagulant therapy after lar ejection fraction in inferior infarction are available from thrombolytic therapy. The Netherlands trial (l3), in which seven trials (3,10,26,27.33-35.) (Table 3). All show preser- time to treatment was relatively brief and patency rate? were vation of left ventricular ejection fraction in treated patients highest. demonstrated the best short-term survival benefit ;,I compared with control patients. The Western Washington treated patients. Further support for survival benefit in trials did not show a statistically significant difference. but patients with inferior myocardial infarction treated with the average time to treatment in the intracoronary trial was much longer than in the other trials. whereas the intravenous trial reported data from only 52% of the patients. The best Table 5. Late Mortality in Inferior Myocardia! Infarction results were seen when the time from symptom onset lo - ~--.-- treatment was brief (TIC0 trial) or when patency rates were I%) high (Netherlands trial). The ISAM trial (23) also showed a No. of Treated Control statistically significant improvement in patients treated Tml Pat1entr Group Group within 3 h of symptom onset, but did not publish the WWICSII yrlI1) 134 1.4 6.3 numerical ejection fractions. These results are especially Netherlandr II yr) 051 287 8.6 II 5 impressive given that improvement in ejection fraction is GISSI II yr) 121) 4m3 II.6 12.6 more difficult to demonstra!e when the baseline ejection ISAM I31 mu, I29 877 12.3 16.3 234 II.0 7.0 fraction is >50%, as is often the case in inferior infarction WWIVS I? yrl 127) (38). AbbrevWm\ as I” Table I 48A BATES IACC Vol. 12. No. 6 REPERFUSlON IN INFERIOR MYOCARDIAL INFARCTION December 198R:44A-51A

DlSlZ3l II 14 PDA/PL 3 2

AV = amoventricular: PDA = posterior descending coronary anery: PL = postemlatelal coronary artery: TAMI = Thmmbolysis and Angioplasty in Myocardal Infarction trial: WWICS = Western Washington ln~~oronary Streptokinase trial. thromho$ic therapy was found in the large ISIS-2 trial (39). in which there was a siatistically significant reduciion in morlality in both anterior and inferior infarction after intra- venous streptokinase.

Myocardial Infarct Size The site of infarct artery occlusion and the extent of the arterial distribution are important determinants of infarct Figure 1. Right anterior oblique projections of a nondominant size. circumflexcoronary artery (upperpanel) and a codominanlcircum- Site of infarct artery occlusion (Table 6). Data ?re avail- Rexcoronary artery with alarge posterolaleral branch (lower panel). able on the site of infarct artery occlusion from the WWlCS trial (6) and the TAMI-I trial (Table 6). These trials and others, using ST segmentelevation as entry criteria, have descending or posterior descending artery occlusion and consistently noted that the infarct-related artery is the left with smalldiagonal or marginal branch occlusion. anterior descendingcoronary artery in 40 to 45% of patients, Anatomic variation in coronary artery distribution. The the right coronary artery in 40 to 45% of patients and the left left anterior descending coronary artery consistently gives circumflex coronary artery in IO to IS% of patients. When off perforator branches to the intraventricular septum and the left anterior descending artery is the infarct-related diagonalbranches to the anterolateral wall. The distal artery artery, the site of occlusion is proximal to the first diagonal usually reaches the apex of the ventricle, though it may stop branch in approximately 70% of patients and before the short or wrap around the apex to the diaphragmaticsegment. seconddiagonal branch in another 25%; the distal artery and In contrast, the circum&ex and right coronary arteries have diagonal branches are involved in <5%. When the right more variable anatomy. The posterior descending coronary coronary artery is the infarct-related artery, the site of artery is part of the right coronary circulation in 90% of occlusion is almost always proximal to the entire left ven- patients and the left circumflex artery in 10% of patients. tricular perfusion bed, occurring before the first right ven- Perhaps more important for the purposes of this discussion is tricular branch in 55% of patientsand in the middle and distal the variation in distribution of the posterolateral branches, artery in approximately 43% of patients. In the circumflex which can be small or large, number from one to three and artery, 20% of the occlusions are in an obtuse marginal originate from either the circumflex or the right coronary branch and Ro%are in the atrioventricular (AV) circumflex artery (Fig. I and 2). branch. Thus, it appearsthat theelectrocardiographic (ECG) lschemic burden. When both the site of occlusion of the criterion of ST segmentelevation is very effective in exclud- infarct-related artery and anatomic variation in coronary ingpatients fer thrombo!ytic therapy with distal left anterior artery distribution are considered, it becomes apparent that Fiire 2. Left anterioroblique projections of a codominant right coronary artery (upper panel) and a dominant right coronary artery with large posterolateral branches (lower panel). anterior infarction is a fairly homogeneousentity, whereas inferior infarction is a heterogeneousentity. Anterior infarc- tion almost always involves the anterolateral ventricular segmentand part or all of the left ventricular apex. The high frequency of proximal arterial occlusion usually involves the anteroseptal segment in the infarct as well. In contrast, inferior infarction can be limitedto only the posterobasalor diaphragmaticor posterolateral segments.depending on the size of the infarct-related artery, or it can involve two or three of the segments. Additionally, the apical segmentcan be involved, and if the occlusion is in the proximal right coronary artery, right ventricular infarction can occur con- comitantly. A major limitation in all of the randomized trials is that the variable ischemic burden in inferior myocardial infarction has not been considered in the analyses of left ventricular function or mortality. ECG infarct size. Several studies (40-43) in the last decade have documentedthat the presence of precordial ST segmentdepression in inferior wall myocardial infarction is associated with CK enzyme release, acute left ventricular SOA BATES JACC Vol. 12. No. 6 REPERFUSION IN INFERIOR MYOCARDIAL INFAHCTION Dcccmbcr ,9”R:44A-SIA

Figure 3. Treatment algorithm for patients with inferior myocardial infarction who present within 6 h of symp tom onset. Cath = cardiac catheterization; HTN = hypertension: IV = intravenous; FTCA = percutaneous transluminal coronary angioplasty: rt-PA = recombi- nant tissue plasminogen activator: Rx = treatment: Sx = symp!om onset.

perhaps because of the larger thrombus volume in the right 5. Strauon JR. Speck SM. Caldwell JH, et al. Lale effects of intracoronary sweptokinasc on regional wall molion. vcnlricular aneurysm and Ien coronary arlery (30). The superior efficacy of intravenous venlricular lhrgmbus in myocardial infarction: rc~ults from the Western r&PA versus s!reptokinase in recanalizing older and perhaps Washington randomized trial. J Am Call Cardiol 1985;%1023+3. larger thrornbi is of particular importance in inferior infarc- 6. Stadius ML, Maynard C. Fritz JK. et al. Coronary anatomy and left tion, in which infarct size tends to be smaller and right venlricular function in the lint I2 hours of acute myocardial infarcrion: coronary artery reocclusion rates remain about 20% regard- the Western Washington rdadomized bumcoronary streptokinan trial. Circulation 1985;72:292-301. less of treatment strategy. 7. Stadius ML, Davis K. Maynard C. et al. Risk rtratiticalion for I year Figrrrc 3 presmts a ~rcutn~ct~t crlgoriflrrn for acute inferior survival based on chara&rislics identified in the early hours of acute infarction that takes into consideration the bleeding risk myocardial infarction. The Western Washington intracoronary streptoki- a.sociated with reperfusion therapy and the potential bene- nase trial. Circalalion 1986;74:703-Il. fits of arierial patency and preservation of ventricular func- 8. Simwns ML, Sermys PW. van den Brand M, et al. Improved survival after early thrombolytis in acute myocardial infarction. A randomized tion. The inability of previous trials to demonstrate a sur- trial conducted by the Interuniversity Cardiology lnsthutc in the Ncther- vival benefit in inferior infarction can be explained by lands. LanceI lY85:2:57~2. limitations in study design. It should be expected that when 9. Simwns ML, Serrays PW, van den Brand M. et al. Early thrombolysis in time to treatment is rapid, recanrlization rates are high, left acute myocardial infarction: limitation of infarct size and improved ventricular function is preserved and adequate sample sizes survival. J Am Coil Cardiol 1986?717-28. are tested, then mortality rates can be decreased by reper- IO. Serrays PW. Simwns ML, Saryapranata H. el al. Preservation of global and regional left ventricular fan&n after early thrombolysis in acute fusion therapy independent of infarct location. rnjrocardial infarction. J Am Coil Cardiol 1%7:729-42. - I I. Rcs JCJ. Simoons ML, van der Waal EE. e! al. Long term improvement The secretarial assis;ance of Lisa Hackbarth and the critical review of the m global left venlricala~ fuacdon after early thrombol)tic treatment in manuscripl by Robert C&T, MD. denram Pitt. MD and Eric Top& MD are acute myocardial infarction. Report of a randomised multicentre trial of gratefully acknowledged. inoacoronary streplokinase in acute myocardial infarction. Br Heart J 1986%x414-221. I?. van der Laarsc A. Vermeer F. Hermens WT. et al. Effects of early intrdcoronary streplokinase on infarct size estimated from cumulalive enzyme release and on enzyme release pdle: a randomized trial of 533 References patients whh acute myocardial infarction. Am Heart J 1986:112:672-81. I. Kennedy JW. Atkins JM. Gold&n S. et al. Recent ckdnge, in manage- 13. Vermcer F. Sirnoons ML. Bar FW. el al. Which patients benefit mosl ment of acute myocardlal infarction: implic;‘ion for emergency cafe from early thrombolylic Ihemp) with inwacoronary streptokinase? Cir- physwians. J Am Coil Cardiol 1988:11:446-9. culation 11)86:743137%89. 2. Kennedy JW. Rhchic JL. Davis KB. et al. Western Wall ,ngtoa random- 14. Bar FW. Vemxtr F. de Zwaan C. et al. Value of admission eloctrocar- ized trial of intrncoronnry strep:tikmase in scale myocardizl infarclion. N diogmm in predicting ouIcome of thrombolytic therapy in acute myocw En&: J Med 1983;309:1477-82. dial Infarction. A randomized trial conducted by the Netherlands lnter- 3. Riichic JL. Davis KB. Wilbamr DL. et al. Global and regional Ien university Cardiology Inslitu!e. Am J Cardiol 1987:59:613. ~enlncular function and tomographic radmnucbdc petiusmn: the Western IS. Hugenholtz PG. lschemic heart dixasc: inlrodactory sldteme~l. Am Waslangton inuacoronaq srreplokina.c .n myocardidl iafarcdoa trial. Hear? J 1987;114:230-I. Circulalion 19&1:7l1:867-75. 16 Sways PW. Suryapranald H. Siaoons ML, et al. lntracoronary throm- 4 Kennedy JW. Rilchic JL. Davi\ KR. rl al The Werwm Washington b&sip in palienls with acute myocardial infarction: the Netherlands randomized trial of intrdcoronary strc?tokmase m acute myocardial randomized lrial and current stalus. Circulation 1987:76(suppl ll):ll-63- infarction: a 12.month follow-up report. N Engl 3 Med 1985:312:lOT-8. 78. JACC Vol. 12. No. 6 RATES 51A December 19R8:~A-5lA REPERFIJSION IN INFERIOR MYOCARDIAL INFARCTION

17. Suryapranata H. Scrruys PW, Veneer F. et al. Value of lmmedrale 33. Guercl AD. Gersknblilh G, Bnnker JA, el al. A randomized trial of coronary aagiopk%ly followmg lnlracoronary thrombolyw in PEU~F mlravenws tirwe plasminogn aclivalor for acule myocardii mfarcllon myocardial inhrction. Cathct Cardiovasc Diaan 1987.13223-32 ?uulhrubwquenl randomization lo elective coronary angmplasly. N Engl IS. van der Laarse A, Kerkhof PLM. Vermeer F. et al. Relation belwcen J Med 1987:31~1613-8. infarct size and left ventricular perforraance assessed in patients wth 34. O’Rorrke M. Baron D. Keogh A. et al. Limilabon of myocardial first acole myofardial infarction randomized lo mtrxoronary lhrom- mfarc*wm by early infusion of recombinant tissue-lype ptarmiaoaen bolytic therapy or lo conventiondl lreatmenl Am J Cardiol 1988:61:t-7 aclIvBlor. ClrcuIalion 1988;‘n:131 l-5. 19. Gnlppo Italiaao per lo Studio delta Streptochmasi nell’lnfarlo Miocar- 35. 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