American Heart Journal
Volume 148, Issue 6 , Pages 931-936, December 2004

The continuing importance of prior stroke in STEMI patients

  • Michael A. Sloan, MD, MS, FACC

      Affiliations

    • Department of Neurological Sciences, Rush University Medical Center, 1725 W. , Harrison, Suite 1106, Chicago, IL, USA 60612
    • Corresponding Author InformationPhone 312-942-4500, FAX 312-563-3495,

Article Outline

 

See related article on page 1012.

In the pre-fibrinolytic era, stroke occurred in 1.7-3.2% of acute ST-segment elevation myocardial infarction (STEMI) patients, typically in the first week (one third within 24 hours). Associated factors included anterior or apical MI, large infarct size, atrialarrhythmias, cardiac pump failure or Killip Class IV, history of previous MI and history of previous stroke. The mortality from stroke was 54-61%. Most (if not all) strokes were attributed to cerebral embolism (cerebral infarction or CI), and intracranial hemorrhage (ICH) was rare (0.05-0.14% patients treated with anticoagulants).1, 2

Fibrinolytic therapy for acute STEMI is associated with a slight excess risk of stroke (especially ICH) that occurs predominantly within the first day of therapy.2, 3 Most CIs following fibrinolytic therapy for acute STEMI occur more than 48 hours after treatment for myocardial infarction.4, 5, 6, 7 Anterior wall myocardial infarction has been associated with CI in many7, 8, 9 but not all10, 11 studies. The overall range (mean) frequencies of stroke subtypes in large comparative coronary fibrinolysis trials using evaluable fibrinolytic regimens are: total stroke 0.7% to 2.7% (1.34%); ICH 0.08% to 2.7% (0.59%); CI 0.15 to 1.24% (0.52%); unknown cause 0.06% to 0.62% (0.21%); and subdural hematoma 0.01% to 0.15% (0.02%).4, 5, 7, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31 In large coronary fibrinolysis registries, ICH has occurred in 0.88%32 and 1.43%.33 The higher frequencies of ICH in recent trials26, 27, 28, 29, 30 and registries32, 33 may be due to inclusion/treatment of patients at higher risk of ICH (older age, other risk factors), use of bolus fibrinolytic agents,34, 35 and higher heparin doses or activated partial thromboplastin times.36, 37

Risk factors for CI in coronary fibrinolysis trials have been identified. Older age (particularly >/= 70 years) has been strongly associated with CI.5, 8, 11, 13, 14 Poor Killip class has also been strongly associated with CI.5, 8, 11 In GUSTO-I,11 multivariable baseline predictors of CI were older age (per 10 years), increased heart rate (per 10 beats per minute), history of stroke or TIA, diabetes, previous angina and history of hypertension and multivariable in-hospital predictors of CI were Killip class, atrial fibrillation/flutter, coronary artery bypass surgery, and cardiac catheterization. A multivariable model using baseline historical and clinical factors was developed. A simple nomogram incorporating age, heart rate, history of diabetes mellitus, history of hypertension, previous cerebrovascular disease and history of prior angina can predict the occurrence of CI after fibrinolysis for acute STEMI (c-index=0.68). In TIMI-II,6 28/29 (97%) CIs were felt to be embolic in origin; 17 (59%) showed strong evidence for at least one cardiac abnormality (mural clot, wall motion abnormality, aneurysm, or atrial fibrillation) known to be associated more specifically with embolism than acute myocardial infarction alone. In the Survival and Ventricular Enlargement (SAVE) trial,38 decreased ejection fraction (18% increased risk per every 5% decrease in ejection fraction) was independently associated with long term stroke risk in patients with acute myocardial infarction.

Risk factors for the occurrence of ICH in large coronary thrombolysis trials5, 7, 13, 14, 15, 29, 39, 40 and registries32, 33 have been identified. These include age, low body weight, prior cerebrovascular disease, diastolic blood pressure, hypertension, systolic blood pressure, excess pulse pressure, thrombolytic choice and dose, gender, race, anticoagulant therapy at study entry, dementia, head or face trauma, and use of concomitant medications. Several clinical trials5, 7, 41 and registries32, 33 have shown that prior cerebrovascular disease is a moderately strong risk factor for ICH. In GUSTO-1,7 2% of the study population had a history of cerebrovascular disease. Of 526 patients with a history of transient ischemic attack, 2.9% had ICH. Of 293 patients with a history of stroke, 2.4% had ICH. In NRMI-2,32 a history of prior stroke mitigated the effect of advancing age on ICH risk in both men and women. The risk of ICH after fibrinolytic therapy for acute STEMI can be predicted for individual patients.7, 32, 33, 39, 41 In CCP33 and InTIME-2,41 risk stratification scores were developed to estimate the risk of ICH for individual patients, with an ICH risk of 0.25%-0.68% for patients with 0-1 risk factor to 4.11%-4.50% for patients with ≥5 risk factors. The c-indices for the GUSTO-1, NRMI-2 and InTIME-2 models range from 0.547 to 0.74,32 suggesting that much discriminating power resides in other variables, such as history of head/facial trauma, syncope, or dementia.42

In placebo-controlled trials or comparative studies using streptokinase,4, 12, 17 recombinant tissue type plasminogen activator5, 21, 24, 25 and anisoylated plasminogen-streptokinase activator complex,43, overall stroke-related mortality was similar between treatment (42%) and control (37%) groups.1 In GUSTO-1,7 41% of all stroke patients died, with no significant differences in stroke mortality rates between the four thrombolytic/antithrombotic regimens. However, mortality rate varied by stroke subtype: 44%23 to 60%7 for ICH, 17%7 to 57%24 for CI, 12.5% 6 to 32.4%7 for HI and 54.8% 13 to 72.1%7 for stroke of unknown cause. In ISIS-2,9 TIMI-2,5 and GUSTO-1,7 there was no difference in the occurrence of major or disabling stroke between the various treatment and control groups7, 9 or between ICH and CI patients.5 The occurrence of stroke results in reduced utilization of cardiac procedures, increased length of stay, and significantly higher baseline and follow-up medical costs as indicated by the need for institutional care, especially in ICH patients.44 Mortality rates from CI following coronary fibrinolysis for acute STEMI decreased from the prefibrinolytic era to the fibrinolytic era in some studies (ref. 7% – 17%) but not others (ref 24% – 57%; ref. 45% – 40%). Risk factors for fatal CI following acute MI include older age, high blood pressure, history of diabetes mellitus, history of peripheral vascular disease, history of coronary heart disease and cigarette smoking.45, 46

Data from recently published registries and clinical trials indicate that prior cerebrovascular disease is an important determinant of long-term outcome in patients with coronary artery disease.47, 48, 49 Individuals with prior cerebrovascular disease tend to be older, have higher frequencies of cardiovascular risk factors, and higher frequencies of multivessel coronary artery disease.47, 48, 49 In addition, these individuals have an approximately 2-fold increase in mortality over 1-5 year follow-up,47, 48 an increased hazard of death, re-infarction, recurrent ischemia, stroke and a composite of these events over 10 months of follow-up.49 These individuals may be at a 3-fold increased risk of subsequent TIA and stroke.49 Of great concern is the observation that patients with prior cerebrovascular disease receive less aggressive therapy with beta-blockers and hypolipemic agents.48, 49

There is both legitimate concern and confusion surrounding the issue of whether fibrinolytic therapy should be contraindicated in patients with a history of prior cerebrovascular disease. In TIMI-2,5 the reduction of ICH occurrence from 2.5% with 150 mg to 1.1% with 100 mg tissue plasminogen activator also reflects the influence of the other three protocol changes: use of aspirin 80 mg was postponed for 24 hours, patients who ever had a history of stroke or intermittent cerebral ischemic attacks were made ineligible for the study, and patients with blood pressures >/= 180 systolic or ≥110 diastolic were excluded. The 1996 ACC/AHA Guidelines for the Management of Acute Myocardial Infarction50 stated that “Previous hemorrhagic stroke at any time; other strokes or cerebrovascular events within 1 year” was a contraindication to use of fibrinolytic therapy and that “History of prior cerebrovascular accident or known intracerebral pathology not covered in contraindications” was a caution/relative contraindication. These statements were “Viewed as advisory for clinical decision making and may not be all-inclusive or definitive.” In more recent small and large coronary thrombolysis trials,19, 20, 26, 27, 28, 29, 30, 31 the use of prior TIA or stroke as an exclusion criterion has varied: stroke within 2 years,31 TIA within 6 months/any history of stroke,20 any stroke,19, 26, 27 and any history of prior TIA or stroke.28, 29, 30 The reported frequency of ICH in patients older than 75 years has been 0.5% with streptokinase and heparin,20 2.2% percent with pre-hospital tenecteplase and enoxaparin51 and 2.5% with reteplase.26 Giugliano et al37 have shown that the higher ICH frequencies with the bolus agents lanoteplase or tenecteplase may in part be explained by the effect of the heparin bolus (InTIME-2=1.12%, InTIME-IIb=0.50%) and dose of the heparin infusion (ASSENT-1 and TIMI-10B: higher heparin dose = 1.83%, lower heparin dose = 0.74%). In the Maximal Individual Therapy in Acute Myocardial Infarction (MITRA) registry,52 previous stroke within three months was the strongest predictor of stroke (OR= 9.3, 95% CI = 6.0-14.2) after acute MI. However, the type of stroke within three months of MI, the type of stroke after MI, and whether or not the stroke patients received fibrinolytic therapy was not specified. Based upon limited information regarding prior stroke and transient ischemic attack in recent publications from the most recent clinical trials, it appears that the effect of prior stroke/transient ischemic attack per se on the frequency of ICH may be exaggerated by the effects of age greater than 75 years, heparin bolus and prolonged activated thromboplastin times.

Two recent meta-analyses53, 54 of 23 randomized trials involving 7,739 fibrinolysis-eligible patients comparing primary percutaneous transluminal coronary angioplasty (PTCA) and various fibrinolytic therapy regimens for acute STEMI show that the frequency of stroke (total and hemorrhagic) may be less with PTCA. Consistently lower frequencies of total stroke and ICH were observed following PTCA compared with streptokinase, tissue plasminogen activator within 3-4 hours of symptom onset and accelerated tissue plasminogen activator infusion. The pooled frequency of total stroke was 1.0% for PTCA and 2.0% for thrombolysis (OR = 0.46, 95% CI = 0.30-0.72). In addition, the pooled frequency of hemorrhagic stroke was 0.05% for PTCA and 1.14% for fibrinolysis (OR = 0.05, 95% CI = 0.006-0.35).

It is in this context that Cooper et al.55 in this issue report on the significance of prior stroke in STEMI patients enrolled in the Magnesium in Coronaries (MAGIC) trial. Of the 6,213 patients enrolled in MAGIC, 558 (9%) had a history of prior stroke, emphasizing the importance of this patient subgroup. This study confirmed the findings of other investigators47, 48, 49 by showing that patients with prior stroke were significantly more likely to have a history of hypertension, diabetes, myocardial infarction, and congestive heart failure. Novel features of the study were as follows. Patients with prior stroke had higher mean Thrombolysis in Myocardial Infarction (TIMI) risk scores than patients without prior stroke (4.37 vs. 3.93, P < .0001). Fibrinolysis-eligible patients with prior stroke were significantly less likely to receive reperfusion therapy (66.3% vs. 80.6%) and more likely to receive primary percutaneous coronary intervention (PCI) (20.5% vs. 8.1%). In-hospital stroke (3% vs. 1%), severe congestive heart failure (23.3% vs. 18.2%) and 30-day mortality (21.0% vs. 14.7%) were significantly higher in patients with prior stroke. Mortality from in-hospital stroke was 56%. In a multivariable analysis, prior stroke was independently and significantly associated with a higher risk of death at 30 days after adjusting for individual components of the TIMI Risk Score (OR = 1.44, 95% CI = 1.14-1.82, P = .0023, c index = 0.732).

The TIMI Risk Score for STEMI was originally developed in the InTIME-II trial and externally validated in the TIMI-9A trial as a convenient and powerful bedside tool to predict mortality risk upon presentation and permit risk stratification.56 This tool was applied to the National Registry of Myocardial Infarction-3 dataset and was shown to have similar discriminative power among patients treated with fibrinolytics (c index = 0.79) and PCI (c index = 0.80).57 Thus, the TIMI Risk Score has utility across the entire spectrum of patients presenting with STEMI. The data of Cooper, et al. strongly suggest that prior stroke be included in a revised TIMI Risk Score in order to further improve risk stratification for STEMI patients.

The preferential use of PCI as reperfusion therapy in STEMI patients with prior stroke in the MAGIC trial might have reflected the concern regarding ICH as a complication of fibrinolytic therapy33, 39, 41 and reported summary observations of reduced total and hemorrhagic stroke with PCI.53, 54 However, due to the inclusion criteria of the MAGIC trial, it could not be determined if use of reperfusion therapies varied according to TIMI Score strata. In addition, detailed information regarding a history of transient ischemic attacks and the type of prior stroke were not collected and brain images to evaluate adverse neurological events in the trial were not required by the study protocol. It is not possible to know if patients who received fibrinolytics in the MAGIC trial were more likely to have a history of prior hemorrhagic stroke and had ICH as a complication. Future clinical trials comparing pharmacologic and PCI strategies for STEMI, excluding patients with prior ICH, should include evaluation of brain images in patients with stroke-like events in order to address the issues of whether outcomes in STEMI patients with prior stroke differ according to TIMI Score and reperfusion strategy.

At this time, the results of Cooper et al55 provide physicians with implicit suggestions on how to reduce the short-term and long-term mortality and morbidity in STEMI patients with prior stroke. Risk factors for 30-day mortality, as identified by the TIMI Risk Score, should be aggressively managed to reduce their impact. Prior stroke patients, especially those who have or develop (severe) congestive heart failure, should receive optimal treatment according to national guidelines in order to reduce short-term morbidity and mortality. Patients at risk for in-hospital stroke can be identified using predictive models for CI11 and ICH.33, 39, 41 Reperfusion-eligible patients at unacceptably high risk of ICH should probably be transferred to centers where PCI can be performed in a timely and effective manner, assuming coronary anatomy is suitable. Patients at high risk of CI can be identified by the GUSTO-1 instrument11 and echocardiographic features.6, 38 In clinical trials comparing moderate (INR 2-3) or high (INR 2.8-4.2) intensity warfarin and aspirin to aspirin alone,58, 59, 60 there was a significant 29-61% reduction in risk of death, recurrent myocardial infarction and thromboembolic stroke with combination therapy. In a trial comparing high (INR 2.8-4.2) intensity warfarin and aspirin to aspirin alone,60 there was a statistically significant 48% reduction in thromboembolic stroke in patients receiving combination therapy in a pre-specified secondary analysis. In the Survival and Ventricular Enlargement trial,38 use of aspirin and anticoagulant therapy were each independently associated with a decreased risk of stroke (aspirin: OR = 0.49, 95% CI = 0.29-0.65; anticoagulant therapy: OR = 0.19, 95% CI = 0.13-0.27; each P < .001).

In the absence of guidance from a homogeneous clinical trial of STEMI patients with sufficient sample size and power, one may take the following approach to prevention of in-hospital stroke in this setting. If the predicted probability of CI is higher or lower than expected from the natural history and a cardiac source of embolism other than acute myocardial infarction is present (i.e., atrial fibrillation, left ventricular thrombus, congestive heart failure, etc.), then aspirin and long-term anticoagulation should be strongly considered. If the predicted probability of CI is lower than expected from the natural history and evidence for a strong cardiac source of embolism and severe extracranial stenosis is absent, then appropriate antiplatelet therapy may be administered. Since there is no proven therapy which reduces mortality from stroke, it is prudent to modify stroke risk factors and prevent the stroke in the first place.

Since prior cerebrovascular disease is associated with higher frequencies of risk factors, long-term mortality and stroke recurrence in patients with coronary artery disease, a multifaceted approach appears warranted. First, aggressive treatment and control of risk factors for both cardiovascular and cerebrovascular disease is needed. Numerous studies have shown that hypertension, diabetes, atrial fibrillation and hypercholesterolemia are not adequately treated in the population. For hospitalized patients, smoking cessation counseling is now a quality indicator for cardiovascular and stroke care. This is an important area of concern for cardiologists and primary care physicians alike. Second, it would be valuable for physicians to better understand the mechanism of the prior stroke event in STEMI patients, so that effective, appropriate medical therapies and interventions can be prescribed. If the stroke diagnosis is unclear, it may be necessary to seek neurologic consultation for stroke diagnosis and to assist with choice of therapy(ies) for optimal patient care. In this way, joint cardiologic and neurologic issues can be effectively managed.

In summary, the results of Cooper et al remind us all of the importance of prior stroke in the STEMI patient. The authors correctly point out that as the population ages, the burden of combined cardiovascular/cerebrovascular disease will grow. We must be prepared to take concerted action and reduce the morbidity and mortality in this ever enlarging and challenging patient group.

Back to Article Outline

References 

  1. Sloan MA, Gore JM. Ischemic stroke and intracranial hemorrhage following thrombolytic therapy for acute myocardial infarction: A risk-benefit analysis. Am J Cardiol. 1992;69:21A–38A
  2. Sloan MA. Neurologic complications of thrombolytic therapy. In:  Biller J editors. Iatrogenic Neurology. Boston: Butterworth Heinemann; 1997;p. 335–378
  3. Fibrinolytic Therapy Trialists (FTT) Collaborative Group . Indications for fibrinolytic therapy in suspected acute myocardial infarction: Collaborative overview of early mortality and major morbidity results from all randomized trials of more than 1000 patients. Lancet. 1994;343:311–322
  4. ISIS-2 (Second International Study of Infarct Survival) . Randomized trial of intravenous streptokinase, oral aspirin, both or neither among 17,187 cases of suspected acute myocardial infarction: ISIS-2. Lancet. 1988;ii:349–360
  5. Gore JM, Sloan M, Price TR, et al.  TIMI Investigators   Intracerebral hemorrhage, cerebral infarction, and subdural hematoma after acute myocardial infarction and thrombolytic therapy in the thrombolysis in myocardial infarction study: Thrombolysis in Myocardial Infarction, Phase II, Pilot and Clinical Trial. Circulation. 1991;83:448–459
  6. Sloan MA, Price TR, Terrin ML, et al.  TIMI Investigators   Ischemic cerebral infarction after rt-PA and heparin therapy for acute myocardial infarction. The TIMI-II Pilot and Randomized Trial combined experience. Stroke. 1997;28:1107–1114
  7. Gore JM, Granger CB, Simoons ML, et al.  GUSTO-I Investigators   Stroke after thrombolysis: Mortality and functional outcomes in the GUSTO-I trial. Circulation. 1995;92:2811–2818
  8. Maggioni AP, Franzosi MG, Farnia ML, et al.  GISSI Group   Cerebrovascular events after myocardial infarction: Analysis of the GISSI trial. Br Med J. 1991;302:1428–1431
  9. Tanne D, Goldbourt U, Zion M, et al.  SPRINT Study Group   Frequency and prognosis of stroke/TIA among 4808 survivors of acute myocardial infarction. Stroke. 1993;24:1490–1495
  10. Bodenheimer MM, Sauer D, Shareif B, et al.  Relation between myocardial infarction location and stroke. J Am Coll Cardiol. 1994;24:61–66
  11. Mahaffey KW, Granger CB, Sloan MA, et al.  GUSTO-I Investigators   Risk factors for in-hospital nonhemorrhagic stroke in patients with acute myocardial infarction treated with thrombolysis: Results from GUSTO-I. Circulation. 1998;97:757–764
  12. Gruppo Italiano per lo Studio della Streptochinasi nell'Infarto Miocardico (GISSI) . Effectiveness of intravenous thrombolytic treatment in acute myocardial infarction. Lancet. 1986;i:397–402
  13. Gruppo Italiano per lo Studio della Sopravvivenza nell'Infarto Miocardico . GISSI-2: A factorial randomized trial alteplase versus streptokinase, and heparin versus no heparin among 12,490 patients with myocardial infarction. Lancet. 1990;336:65–71
  14. International Study Group . In-hospital mortality and clinical course of 20,891 patients with suspected acute myocardial infarction randomized alteplase and streptokinase with or without heparin. Lancet. 1990;336:71–75
  15. de Jaegere PP, Arnold AA, Balk AH, Simoons ML. Intracranial hemorrhage in association with thrombolytic therapy: Incidence and clinical predictive factors. J Am Coll Cardiol. 1992;19:289–294
  16. ISIS-3 (Third International Study of Infarct Survival) Collaborative Group . ISIS-3: A randomized comparison of streptokinase vs. tissue plasminogen activator vs. anistreplase and of aspirin plus heparin vs. aspirin alone among 41,299 cases of suspected acute myocardial infarctions. Lancet. 1992;339:753–770
  17. EMERAS (Estudio Multricentrico Estreptoquinasa Republicas de America del Sur) Collaborative Group . Randomized trial of late thrombolysis in patients with suspected acute myocardial infarction. Lancet. 1993;342:767–772
  18. The Global Use of Strategies to Open Occluded Coronaries (GUSTO) IIa Investigators . Randomized trial of intravenous heparin versus recombinant hirudin for acute coronary syndromes. Circulation. 1994;90:1631–1637
  19. International Joint Efficacy Comparison of Thrombolytics . Randomised, double-blind comparison of reteplase double-bolus administration with streptokinase in acute myocardial infarction (INJECT): Trial to investigate equivalence. Lancet. 1995;346:329–336
  20. The Hirulog and Early Reperfusion or Occlusion (HERO)-2 Trial Investigators . Thrombin-specific anticoagulation with bivalirudin versus heparin in patients receiving fibrinolytic therapy for acute myocardial infarction: The HERO-2 randomised trial. Lancet. 2001;358:1855–1863
  21. Wilcox RG, Olsson CG, Skene AM, et al.  Trial of tissue plasminogen activator for mortality reduction in acute myocardial infarction: Anglo-Scandinavian Study of Early Thrombolysis (ASSET). Lancet. 1988;ii:525–530
  22. O'Connor CM, Califf RM, Massey EW, et al.  Stroke and acute myocardial infarction in the thrombolytic era: Clinical correlates and long term outcome. J Am Coll Cardiol. 1990;16:533–540
  23. Kase CS, Pessin MS, Zivin JA, et al.  Intracranial hemorrhage after coronary thrombolysis with tissue plasminogen activator. Am J Med. 1992;92:384–392
  24. Longstreth WT, Litwin PE, Weaver WD  MITI Project Group . Myocardial infarction, thrombolytic therapy, and stroke: A community study. Stroke. 1993;24:587–590
  25. LATE Study Group . Late assessment of thrombolytic efficacy (LATE) study with alteplase 6-24 hours after onset of acute myocardial infarction. Lancet. 1993;342:759–766
  26. The Global Use of Strategies to Open Occluded Coronary Arteries (GUSTO-III) Investigators . A comparison of reteplase with alteplase for acute myocardial infarction. N Engl J Med. 1997;337:1118–1123
  27. The Continuous Infusion versus Double-Bolus Administration of Alteplase (COBALT) Investigators . A comparison of continuous infusion of alteplase with double-bolus administration for acute myocardial infarction. N Engl J Med. 1997;337:1124–1130
  28. Assessment of the Safety and Efficacy of a New Thrombolytic (ASSENT-2) Investigators . Single-bolus tenecteplase compared with front-loaded alteplase in acute myocardial infarction: The ASSENT-2 double-blind randomized trial. Lancet. 1999;354:716–722
  29. The InTIME-II Investigators . Intravenous NPA for the treatment of infracting myocardium early. InTIME-II, a double-blind comparison of single-bolus lanoteplase vs. accelerated alteplase for the treatment of patients with acute myocardial infarction. Eur Heart J. 2000;21:2005–2013
  30. The assessment of the Safety and Efficacy of a New Thrombolytic Regimen (ASSENT-3) Investigators . Efficacy and safety of tenecteplase in combination with enoxaparin, abciximab, or unfractionated heparin: The ASSENT-3 randomised trial in acute myocardial infarction. Lancet. 2001;358:605–613
  31. The GUSTO-V Investigators . Reperfusion therapy for acute myocardial infarction with fibrinolytic therapy or combination reduced fibrinolytic therapy and platelet glycoprotein IIB/IIIa inhibition: The GUSTO-V randomized trial. Lancet. 2001;357:1905–1914
  32. Gurwitz JH, Gore JM, Goldberg RJ, et al.  Participants in the National Registry of Myocardial Infarction 2   Risk for intracranial hemorrhage after tissue plasminogen activator treatment for acute myocardial infarction. Ann Intern Med. 1998;129:597–604
  33. Brass LM, Lichtman JH, Wang Y, et al.  Intracranial hemorrhage associated with thrombolytic therapy for elderly patients with acute myocardial infarction: Results from the Cooperative Cardiovascular Project. Stroke. 2000;31:1802–1811
  34. Mehta SR, Eikelboom JW, Yusuf S. Risk of intracranial haemorrhage with bolus versus infusion thrombolytic therapy: A meta-analysis. Lancet. 2000;356:449–454
  35. Llevadot J, Giugliano RP, Antman EM. Bolus fibrinolytic therapy in acute myocardial infarction. JAMA. 2001;286:442–449
  36. Granger CB, Hirsh J, Califf RM, et al.  Activated partial thromboplastin time and outcome after thrombolytic therapy for acute thrombolytic therapy: Results from the GUSTO-I trial. Circulation. 1996;93:870–878
  37. Giugliano RP, McCabe CH, Antman EM, et al.  Lower dose heparin is associated with lower rates of intracranial hemorrhage. Am Heart J. 2001;141:742–750
  38. Loh E, St. John Sutton M, Wuh CC-C, et al.  Ventricular dysfunction and the risk of stroke after myocardial infarction. N Engl J Med. 1997;336:251–257
  39. Simoons ML, Maggioni AP, Knatterud G, et al.  Individual risk assessment for intracranial hemorrhage during thrombolytic therapy. Lancet. 1993;342:1523–1528
  40. Selker HP, Beshansky JR, Schmid CH, et al.  Presenting pulse pressure predicts thrombolytic therapy-related intracranial hemorrhage: Thrombolytic Predictive Instrument (TPI). Circulation. 1994;90:1657–1661
  41. Sloan MA, Giugliano RP, Thompson SL, et al.  Prediction of intracranial hemorrhage in the InTIME-II trial. J Am Coll Cardiol. 2001;37(Suppl. A):372A
  42. Kandzari DE, Granger CB, Simoons ML, et al.  GUSTO-1 Investigators   Risk factors for intracranial hemorrhage and nonhemorrhagic stroke after fibrinolytic therapy (from the GUSTO-1 Trial). Am J Cardiol. 2004;93:458–461
  43. AIMS Trial Study Group . Effect of intravenous APSAC on mortality after acute myocardial infarction: Preliminary report of a placebo-controlled clinical trial. Lancet. 1988;i:545–549
  44. Tung CY, Granger CB, Sloan MA, et al.  GUSTO-I Investigators   Effects of stroke on medical resource use and costs in acute myocardial infarction. Circulation. 1999;99:370–376
  45. Tanne D, Gottlieb S, Hod H, et al.  Secondary Prevention Reinfarction Israeli Nifedipine Trial (SPRINT) and Israeli Thrombolytic Survey Groups   Incidence and mortality from early stroke associated with acute myocardial infarction in the prethrombolytic and thrombolytic eras. J Am Coll Cardiol. 1997;30:1484–1490
  46. Tanne D, Yaari S, Goldbourt U. Risk profile and prediction of long-term ischemic stroke mortality: A 21-year follow-up in the Israeli Ischemic Heart Disease (IIHD) Project. Circulation. 1998;98:1365–1371
  47. Tanne D, Gottlieb S, Caspi A, et al.  Israeli Thrombolytic National Survey Group   Treatment and outcome of patients with acute myocardial infarction and prior cerebrovascular events in the thrombolytic era. Arch Intern Med. 1998;158:601–606
  48. Reicher-Reiss H, Jonas M, Tanne D, et al.  Benzafibrate Infarction Prevention (BIP) Study Group   Prognostic significance of cerebrovascular disease in 11,526 chronic coronary artery disease patients. Am J Cardiol. 1998;82:1532–1535
  49. Cotter G, Cannon CP, McCabe CH, et al.  OPUS-TIMI 16 Investigators   Prior peripheral arterial disease and cerebrovascular disease are independent predictors of adverse outcomes in patients with acute coronary syndromes: Are we doing enough?. Results from the Orbofiban in Patients with Unstable Coronary Syndromes-Thrombolysis In Myocardial Infarction (OPUS-TIMI) 16 study. An Heart J. 2003;145:622–627
  50. Ryan TJ, Anderson JL, Antman EM, et al.  ACC/AHA guidelines for the management of patients with acute myocardial infarction. J Am Coll Cardiol. 1996;28:1328–1428
  51. Wallentin L, Armstrong P, Granger C, van de Werf F  ASSENT-III PLUS Investigators . Assessment of the safety and efficacy of a new thrombolytic regimen in the pre-hospital setting (ASSENT-III PLUS). Circulation. 2002;106(23):2986a
  52. Wienbergen H, Schiele R, Gitt AK, et al.  MIR and MITRA Study Groups   Incidence, risk factors, and clinical outcome of stroke after acute myocardial infarction in clinical practice. Am J Cardiol. 2001;87:782–785
  53. Weaver WD, Simes RJ, Betriu A, et al.  Comparison of primary coronary angioplasty and intravenous thrombolytic therapy for acute myocardial infarction. A quantitative review. JAMA. 1997;278:2093–2098
  54. Keeley EC, Boura JA, Grines CL. Primary angioplasty versus intravenous thrombolytic therapy for acute myocardial infarction: A quantitative review of 23 randomised trials. Lancet. 2003;361:13–20
  55. Cooper HA, Domanski MJ, Rosenberg Y, et al. and the MAGIC Trial Investigators: Acute ST-segment elevation myocardial infarction and prior stroke – An analysis from the Magnesium in Coronaries (MAGIC) trial. Am Heart J 2004;xx:yyy-yyy
  56. Morrow DA, Antman EA, Charlesworth A, et al.  TIMI Risk Score for ST-elevation myocardial infarction: A convenient, bedside clinical score for risk assessment at presentation. An Intravenous nPA for Treatment of Infarcting Myocardium Early II Trial substudy. Cir-culation. 2000;102:2031–2037
  57. Morrow DA, Antman EA, Parsons L, et al.  Application of the TIMI Risk Score for ST-elevation MI in the National Registry of Myocardial Infarction 3. JAMA. 2001;286:1356–1359
  58. The Organization to Assess Strategies in Ischemic Syndromes (OASIS) Investigators . Effects of long-term moderate-intensity oral anticoagulation in addition to aspirin in unstable angina. J Am Coll Cardiol. 2001;37:475–484
  59. van Es RF, Jonker JJC, Verheught FWA, et al.  Antithrombotics in the Secondary Prevention of Events in Coronary Thrombosis-2 (ASPECT-2) Research Group   Aspirin and coumadin after acute coronary syndromes (the ASPECT-2 study): A randomised controlled trial. Lancet. 2002;360:109–113
  60. Hurlen M, Abdelnoor M, Smith P, Erikssen J, Arnesen H. Warfarin, aspirin, or both after myocardial infarction. New Engl J Med. 2002;347:969–974

PII: S0002-8703(04)00403-X

doi:10.1016/j.ahj.2004.06.010

Refers to article:

  • Acute ST-segment elevation myocardial infarction and prior stroke: An analysis from the Magnesium in Coronaries (MAGIC) trial

    Howard A. Cooper, Michael J. Domanski, Yves Rosenberg, James Norman, Judith H. Scott, Susan F. Assmann, Sonja M. McKinlay, Judith S. Hochman, Elliott M. Antman, the MAGIC Trial Investigators
    American Heart Journal December 2004 (Vol. 148, Issue 6, Pages 1012-1019)

American Heart Journal
Volume 148, Issue 6 , Pages 931-936, December 2004

Article Tools