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ester and New York, New York f stroke is increased after myocardial infarction close association between anterior myocardial infarction and left ventricu ‘on that embo~i~ati~n a tant cause of stroke i a reviews (5-8) recommend obtaining an in patients with an anterior myoca~djal viding anticoagulant therapy if thrombus is d, a~tbo~~b this procedure is not accepted universally (9). Yet, prospective studies have reported varying degrees of success with the use of anticoagulants to prevent tbrombus (W-14) or reduce the likelihood of stroke (12-18). From the Division of Cardiology, The Harris Chasanoff Heart Ins&% Department of Medicine, Long Island Jewish Medical Center, New Hyde Park and Long Island Campus for the Albert Einstein College OF Medicine, Bronx; *Department of Preventive Medicine and Community Health and Department of Medicine. University of Rochester Medical Center, Rochester; and tDepartment of Biostatistics, Columbia University, New York, New York. This study was supported by a consortium grant from Godecke Aktiengesellschaft, Freiburg, Germany: Laboratories Dr Esteve, SA, Barcelona, Spain; Marion Laboratories, Inc.. Kansas City, Missouri; Nordic Laboratories, Inc., Laval, Quebec, Canada; Lars Synthelabo, Paris, France; Tanabe Seiyaku Co. Ltd., Osaka. Japan: an4 Warner-Lambert International, Morris Plains, New Jersey. Manuscript received December 3. 1993; revised manuscript received Fe : Dr. Monty M. Bodenheimer, Chief of Cardiology, The Harris Chasanoff Heart Institute, Room 2135, Long Island Jewish Medical Center, New Hyde Park, New York 11042. 81994 by the American College of Cardiology ardial infarction ~othes~zed that if tI nterior infarction is with anterior infarction increased incidence of stroke. sbou trospective review of the in the Multicenter from February 17, 1983 to June 30, 1986. The rec~~tment procedure and inclusion and exclusion criteria have been previously reported (19). In brief, men or women 25 to 75 years old who were admitted to the hospital and subsequently documented to have had an acute myocardial infarction were eligible. Patients were excluded if there was evidence of ongoing cardiogenic shock, pulmonary h e at~iovent~c~~ar block or other c ce survival. randomization took during hospital days 3 to I5 (median day 8) from the ti onset of the myocardial infarction. ths (averAll patients were followed up for 12 to 52 age 25 months). Patients were seen by the investigator or or both, at periodic intervals throughout the trial. The MDPIT follow-up schedule consisted of five clinical coordinator, 07351097/94/$7.aQ 62 JACCVol. 24. No. I July 19%61-6 BODENHEIMER ET AL. STROKE AND MYOCARDIAL INFARCT SITE 1. ClinicalCharacteristicsby MyocardialInfarct Site Covariate (no. of patients with anterior, nonanterior infarction) Age 260 yr (724, 1,740) Previous Ml (723. 1,739) NYIIA class II-IV (724. 1,740) History of hypertension (723, 1,739) Insulindependent diabetes (724, 1,740) Cigarette smoking (72 I, 1,727) Cardiachndings Systolic BP cl00 mm IIg (722, 1,734) Bibasiiar pulmonary rales (721,1,733) Cteatine kinase ~619 IJ (724, 1,739) brillation (724, 1,740) sis (at index MI) (724, 1,746) Aspirin adrenergic blocking agents abs ridamole Other antipkitelet agents Reinfatction (before CVA) (724. !,74ft! Warfaiin (at discharge) (724, 1,740) StroktiIA (724, 1.740)” Site uf MI (%I Anterior Nonanterior v:ue 0.795 0.002 a.553 0.886 0.243 0.055 50 25 19 38 9 46 51 20 18 38 8 50 2 4a 79 9 56 I2 5 36 62 8 17 7 0. e 0. < 0. 0. < 0. < 0. 22 49 23 8 9 0.28 19 3 24 56 IO 7 6 0.34 4 4 0.145 0. ==z0. 0. 0.003 0.785 0.381 ‘Total t!Jmber of cerebrovascular events during follow-up (see text). BP = blood pressure; CVA = cerebrovascular accident; EF = eiection fraction: MI = myocardia! infarction; NYHA class = New York Heart Associatiun functional class; TIA i transient ischemic attack. visits in the first year (an initial visit at I month followed by a visit every 3 months), then a visit every 4 months until study closure. Bata retrievalat the clinic visit consisted of an interval medical and cardiac history, review of concurrent medications and physical examinations. During these visits any adverse experiences or intervening medicalconditions, or both, were noted and described on the clinical record forms. Stroke was not coded separately but included as either an adverse event or an interval medical event. As a result, 1,731 medical follow-up repcsrts had to be reviewed. This review was performed by two of us (D.S. and B.S.) without knowledge of the site of the index myocardial infarction. A stroke was defined as an acute focal cerebra) disorder’that resulted in localizing findings characterized by either the patient’s physician or the clinical investitot as a cerebrovascular accident. If the duration of symptoms was ~24 h, the episode was definedas a transient ischemic attack (20).Nonlocalizingsymptoms, such as dizziness, giddiness or wooziness, or involuntary movements, such as limb shaking, were not classified as transient ischemit attacks (20).Because this study was not prospectively designed, confirmationwith computed tomography,ancephalography and other procedures was not always available and was generally not recorded in the patient data. The diagnosisof acute myocardialinfarctionrequiredserum enzyme confirmation:an MBisoenzymefraction>4% of total Creatinekmase (CK)or a qualitativelypositive MB band; an elevatiott of total Iactic deh reversalof the LD or an elevationof 22 times normal of CK, se xaloa?etic transaminaseor LDH in the coronary care unit with a clinically consistent pattern. Acute anterior wail myocardialinfarctionwas defined as Q waves appearing in leads V, to Vd; absence of new Q waves in these leads identifiedpatients with nonanteriormyocatdial infarction(19).The latter group included patients with inferioror posterior Q wave infarction(61%)and those with non-Q wave infarction(39%),defined as elevated serum ent with infarctionwithout Q waves (19). zY Univariateanalysis was performed to determine the relation between baseline clinical variables and infarct site (Table I). A model was then constructed using Cox regression analysis with the occurrence of stroke or transient ischemic attack as the dependent variable (21). All covariates with a p value I 0.10 were forced into the model. The use of warfarin was added to the model to determine its contribution, and it was maintained in the model regardless of its p value. The final model was constructed by adding infarct site to the model (21).Results are expressed as hazard ratio with 95% confidence limits. A Roweranalysiswas performedto determine the possibilityof a beta error (22). The effect of infarct site on time to end point was examined with the method of Kaplan and Meier. The log-rank statistic was used to compare Kaplan-Meier curves. Summary odds ratios were determined with the technique of Mantel and Haenszel(22). Covariates (95% Cl) Value Systolic BP* (on admission to CCU) 1.014 (1.007 to 1.021) < 0.0001 0.930 NS (0.397 to 2.179) 0.F NS Warfarin Anterior i~a~ctiom (0.508 to 1.340) The hazard ratio for sys!olic blood pressure (BP) is per unit increase in , when compared with a patient with a systoli g, a patient with a systolic blood pressure of 150 would have a hazard ratio of 1.014” (=1.97). CCU = coronary care unit; C1 = confidence interval. viva!curvesfor likeli fined RSstroke or attack, in patients wi!la a~it~ri~r or ~Q~~~t~rior m I) at the time of enro~lmc~t. and transient isc s with anterior ~~~a~cti acebo group and 44 ( patients with an event. level and lower cardial infarction as we of admission with the index myoto be treated with infarction had a stroke or transient is pared with 68 (3.9%) of 1,742 patients with a nonanterior myocardial infarction (relative risk 0.82; 95% confidence interval [CI] 0.55 to 1.30).Power analysis revealed that this study had an 86%chance of detecting a relativerisk of stroke of 1.5in patients with anterior versus nonanterior infarction. When the patients with nonanterior infarctionwere classified into those with inferior or posterolateral Q waves a with nap-Q wave infarction, the likelih 3.5% and 4.%, respectively. Figure 1 Meier life table event rate for patients with anterior and r myocardial infarction. As is evident, no signifinona ence exists (p = 0.42 by log-rank test). When cant analyzed by infarct site and treatment with placebo or diltiazem, the findingswere essentially the same (p - 0.35). Multivariate analysis (Table 2). Stepwise multivariate Cox analysis was used to determine variables that were limitingthe screening process to those with anterior infarction (5-S). us ~~rrnat~Q~(Ta A~t~coa~w~~t~~~ an Echocardiographicstudies of the relation between anterior myocardial infarction, thrombus and stroke differ in methstudy oatients, timing of echocardiog~aphy~there including thrombolytic agents) and follow-up. e limitations in mind, pooling these studies shows that the likelihood of thrombus and embolizationin patients with anterior infarction is high whether or not anticoagulants are used (Table 3). In four studies, patients were randomized to receive either anticoagulantsor placebo, althoughthrombolytic agents were sometimes used (1l-14). Two studies (11,12) showed benefit, whereas two (13,l effect on left ventricular thrombus formation. coagulation was studies (I 1-14) were combined, no bus of 1.86 (95% associated with an increased risk of th CI 1.22to 2.82). Thrombolytic agents have been reported to reduce thrombus formation (27,31) or to have no effect (14,18,29,32). However, because anticoagulants are often used concur- 64 JACC Vol. 24, No. I July 1994:61-Q BODENHEIMER ET AL. STROKE AND MYOCARDIAL INFARCT SITE Total No. Study No. With Emboli No. With Thrombus Total No. No. With Thrombus No. With Emboli 497 203 (41%) 24t (4.8%) Norarandomized PooZ Studies 31* (4.7%) 169 (26%) 653 Ref. IO, 15-18,23-32 Randomized Trials of Anticoanulation and Left Ventricular Thrombus Vecchio et al. (14) SCAT) trial (12) Gueret et al. (13) hhnnesilcrnet al. (II) Totals 86 93 25 21 225 26 34 13 7 80 (36%) I 94 2 107 21 1 21 243 2 6 (2.6%) 25 19 0 0 8 I 1 0 52 (21%) 2 (0.8%) ‘21 strokes and IO nonccreblal emboli. K?Ostrokes and 4 noncerebral emboli. SCumulativc odds ratio of thrombus it patients without aflt~coag~~~tjo~ vm.us patients with antic ulation is 1.86 (95% confidence interval 1.22 to 2.82) with a chi-square of 8.36 with I degree of freedom. rently, any benefit may not reflect the effect of throm~o~ytic ents (14). The ability of anticoagulation to prevent stroke is also difficult to assess because of inadequate controls and a relative paucity of embolic events (Table 3). In the present study, warfarin was used in only 1% of patients with anterior infarction, raising the possibility of a type 2 error to he lack of contribution of warfarin to the model. Won on stroke in mtion paof as tlents, The role of anticoagulation in patients after acute myocardial infarction has been the subject of numerous studies. Aithouqh stroke has generally not been a primary prospectively aefined end point, we used previously published analyses (33-35) and a search of MEDLINE to find those randomized studies in which the incidence of stroke could be determined (Table 4) (36-44). As assessed with use ofa cumulative odds ratio and the mantel-~aenszel test (22). the risk of stroke was 2.05 (95% CI I.5 to 2.8) in patients randomized to placebo versus anticoagulation. Left unre- solved is the role of aspirin relative to coMmadi~ in this setting (45). (Table 1). Dexter et al. (4) found a higher than expected rate of stroke. particularly in the 1st 2 months after myocardial infarction. Our study also shows a relatively higher rate within the 1st 2 months, with I8 of 91 strokes occurring during this period. However, the rates were similar for patients with anterior and nonanterior myocardial infarction (Fig. I). Table 4. Analysis of RandomizedStudiesof AnticoagulationAfter Myocardial Infarction: Incidenceof Stroke Control Group Study MRC (36) Wasserman et al. (37) Lovell et al. (38) Ritlsnd et al. (39) MRC (40) Drapkin and Merskey (II) VA Coop (42) Sixty Plus Reinfarction (43) Smith et al. (44) Total* Total No. 188 70 240 101 715 391 499 439 607 3,250 -- No. With Stroke I I 13 2 I8 9 16 21 44 125 Anticoagulation Group Total No. 195 77 172 97 712 145 500 439 No. With Stroke 3 0 2 0 8 13 4 I3 607 20 3,544 63 *Summary odds ratio of stroke in patients in control groupscompared with patients treated with anticoagulation is 2.05 (95% confidence interval I .50 to 2.80) with a chi-square of 20.6 with 1 degree of freedom. MRC = Medical Research Council: VA Coop = Veterans AtEM cooperative study. JACC Vol. 24, No 3uly 1994:61-6 1 5. Ezekowitz MD Acute ~~~~ctio~, left ventricular thrombus and systemic embo~izat~o~. An approach to ma~a8em~nt. J Am Coil Cardiol 1986;6: IZSJ-82. 6. Meltzer RS, Visser CA, Fuster V. ~at~aca~ia~ thro ernb~~~zatio~. Ann Intern 7. Wei~tra~b WS, Ba’albaki concerning the apphcation ofe~~oca~di~g~~by to :he diagnosis and treatment ofmuraltbrombi after anterior wall acme myocaedial infarction. Am J Cardiol1989;64:70816. 8. Editorial. Left ven . ular tbrombus and stroke following myocardial infarction. Lancet 1 ;335:759-60. 9. Cerebral Embolism Task Force. Cardiogenic brain embolism. The second report of the cerebral embolism task force. Arch Nemo1 1989:46:729-43. IQ. T&pie AGG, Robinson JG, Doyle DJ, et al. Comparison of high-dose with lOwdose subcutaneous heparin to prevent left ventricular mural thrombosis in patients with acute transmural anterior myocardial infarction. N Eng! J Med 1989;320:352-7. n Der Lippe 6. Left ventricular ticoagulants in acute myocardial 12. The SCATS Group. Randomised controlled trial of subcutaneous calciumheparin in acute myocardial infarction. Lancet 1989;2:182-6. 13. Gueret P. Dubourg 0, Ferrier A, Farcot JC, Rigaud M, Bourdarias IF. Effects of full-dose hepatin anticoagulation on the development of ventricular thrombosis in acute t~nsmM~al myocardial infarction. 3 Colt Cardiol 1986;8:419-26. prevent more than half of the cere~r~vasc~la~events seen inn our patients. Clearly, further studies are needed to determine the mechanis of these events. U diagnostic criteria exist strokes from those with ot vascular atherosclerosis( review of the ~~~lis~ed agulation even though o therapy. The exact place of this strategy in relation to other interventions remains to be determined with randomized trials (45). We thank Mark Andrews, BA, for help with the data analysis and Shirley Eberly, MS, for assistance with the statistical analysis. I. Fulton RM, Kucket K. Plasma fibrinogen and thromboemboli after myocardial infarction. Lancet 1976;2:1161-4. 2. Thompson PL, Robinson JS. Stroke after acute myocardial infarction: relation to infarct size. Br Med J 1978;2:457-9. 3. Komrad MS, Coffey CE, Coffey KS, McKinnis R, Massey EW, Califf RM. Myocardial infarction and stroke. Neurology 1984;34: 1483-9. 4. Dexter DD, Whisnant JP, Connolly DC, O’Fallon WM. The association of stroke and coronary heart disease: a population study. Mayo Clin Proc 1987:62:1077-83. 14. Vecchio C, Chiarella F, Lupi G, Bellotti P, Domenicucci S. Left ventrict,lar thrombus in anterior acute myocardial infarction tter thrombolysis. Circulation 1991;84:512-9. 15. Keating EC, Gross S, Schlamowitz RA, et al. Mural thrombi in myocardial infarctions. Prospeciive evaluation by two-dimensional ecbocardiography. Am J Med 1983;74:989-95. 16. Weinreich DJ, Burke JF, Pauletto FJ. Left ventricular mural thrombi complicating acute myocardial infarction. Ann Intern Med 1984;100:78994. 17. Johannessen KA, Nordrehaug JE, Bon Der Lippe 6. Stein EV. Risk ems with left ventricular thrombi and acute factors for embolisation in myocardial infarctioo. Br rt J 1988;ti304-10. 18. Keren A, Goldberg S, Gottheb S, et al. Natural history of left ventricular thrombi: their appearance and resolution in the posthospitalization period of acute myocardial infarction. J Am Colt Cardiol 1990;15:798-8 ulricenter Diltiazem Postinfarction Trial Research Croup. The effect of dihiazem ou mortality and reinfarction after myccadial infarction. N Engl1 Med 1988;319:385-92. 20. Koudstaal PJ, Alma A, Pop G&M, Kappelle LJ, Van Latum JC, Van Gijn J, for the Dolch-TJA Study Group. Risk of cardiac events in atypisai transient ischemic attack or minor stroke. Lancet 1992;340:630-3. 21. BMDP Statistical Software Los Angeles CA, Version 1999. Vol I and 2. 22. Fleiss IL. Statistical Methods for Rates and Proportions. 2nd ed. New York: Wiley, 1981:145, 173-5. 23. Friedman M, Carlson K, Marcus FI, Woolfenden JM. Clinical comlalions in patients with acute myocardial infarction and left ventricular thrombus detected by two-dimensional echocardiography. Am J Med 1982:72:894-S. 24. Ezekowitz MD, Kellerman DJ. Smith EO, Streitz TM Detection of aclive left ventricular thrombosis during acute myocardial infarction using indium-11 I platelet scintinraphy. Chest 1984;86:35-9. 25. Johannessen #A. Nordrehag JE, Van Der Lippe G. Left ventricular thrombosis and cerebrovascular accident in acute myocardial infarction. Br Heart 5 1984;51:553-6. 26. Visser CA, Kan G, Meltzer RS, Lie KI. Durrer D. Long term follow-up of left ventricular thrombus after acute myocardial infarction. A twodimensional echocardiographic study ir 96 patients. Chest 1984;86:532-6. 27, Eigler N, Maurer 6, Predimqn SK. Elect of early systemic thromboytic therapy on left ventricular m;r? ::uombus formation in acute anterior myocardial infarction. Am J Cardiol 1934;54:261-3. 28. Spirit0 P, Bellotti P, Chiarella F, Domenicucci S, Sementa A, Vecchio C. Prognostic significance and natural history of left ventricular thrombi in patients with acute anterior myocardial infarction: a two-dimensional echocardiographic study. Circulation 1985;72:774-80. 29. Held AC, Gore JM, Paraskos J, et al. Impact of thrombolytic therapy on 66 BODENHEIMER ET AL. STROKE AND MYOCARDIAL INFARCT SITE left ventricular mural thrombi in acute myocardial infarction. Am J cardiol19@$2310-!. 30. Niiyanno~mulos P, Smith GC, Maseri A, Foale RA. The natural history of left ventricular thrombus in myocardkl i&r&n: a rationale in support of masterly inactivity. J Am Coil Cardiil 1,B9;14:903-11. 31. Lupi G, Domeniczcci S. Chiarella F. Rellotti P, Vecchio C. Jntluenceof thromboylytic ueatme~t followed by full dose anticoagulation on the ~~~~~~v~t~~ tbrombi in acute myocardial infarc!ion. Am :: -. 32. Kupper AF, Verheught FW, Peels CH. Galema I%‘, Roes JP. Left ventricular ihrombus incidence and behavior studied by serial twoy in acute anterior myowdial infarstion: dimenJionat echocard stcmic embolism and oral anticoagulation. J Am CoU Cardid 193!+13:514-20. 33. CbalaKn TC, Matte RJ, Smith H Jr, Kurt&r AM. Evidence favoring the use ofanticoagutants in the hospital phase of acute myocardial infarclion. J Med 1977;297:1091-5. 37. Wasserman AJ, Gutterman LA, Yoe KR, Kemp V Anticoagulants in acute myocardii infarction. Th lation to alter mortahty in a randomized series. A 38. Lovell RRH. Denborougb h4A, Nestel FJ, GobbleAJ. A co~~o~ledtrial of long-term treatment with ant~coa$ula~~ after myocardiat infarction in 412 male patients. Med J Aust 1 cacy of 3 and 12 months’ 39. Ritland S. Lygren T. Compa anticoagulant therapy after myocardial infarction. A controlled clinical trial. hcet l!X9;1:122-4. admi~l~tmtion after cardiac in- Ianl therapy after acute myocardia! iofarcdor~. Results of a c erapy in ~~~e~~ypatients after infarction, Second report in Coronary Thrombosis to hllicino FM. Xuereb RI. Aqt acute myocardhl infarction in