This chapter about fibrinolytic, antiplatelet, and antithrombin treatment for acute ST-segment elevation (STE) myocardial infarction (MI) is part of the American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th Edition). Grade 1 recommendations are strong and indicate that the benefits do, or do not, outweigh risks, burden, and costs. Grade 2 suggests that individual patient values may lead to different choices (for a full understanding of the grading see the chapter by Guyatt et al, CHEST 2008; 133[suppl]:123S-131S). Among the key recommendations in this chapter are the following: for patients with ischemic symptoms characteristic of acute MI of < or = 12 h in duration and persistent STE, we recommend that all undergo rapid evaluation for reperfusion (primary percutaneous coronary intervention [PCI] or fibrinolytic) therapy and have a reperfusion strategy implemented promptly after contact with the health-care system (Grade 1A). For patients with ischemic symptoms characteristic of acute MI of < or = 12 h in duration and persistent STE, we recommend administration of streptokinase, anistreplase, alteplase, reteplase, or tenecteplase over no fibrinolytic therapy (all Grade 1A). For patients with symptom duration < or = 6 h, we recommend the administration of alteplase or tenecteplase over streptokinase (both Grade 1A). We recommend aspirin over no aspirin therapy followed by indefinite therapy (Grade 1A); we also recommend clopidogrel in addition to aspirin for up to 28 days (Grade 1A). In addition to aspirin and other antiplatelet therapies, we recommend the use of antithrombin therapy (eg, unfractionated heparin (UFH), enoxaparin, or fondaparinux) over no antithrombin therapy (Grade 1A), including for those patients receiving fibrinolysis (and regardless of which lytic agent is administered), primary PCI, or patients not receiving reperfusion therapy.

This chapter about antithrombotic therapy for acute myocardial infarction (MI) is part of the Seventh ACCP Conference on Antithrombotic and Thrombolytic Therapy: Evidence Based Guidelines. Grade 1 recommendations are strong and indicate that the benefits do, or do not, outweigh risks, burden, and costs. Grade 2 suggests that individual patients' values may lead to different choices (for a full understanding of the grading see Guyatt et al, CHEST 2004; 126:179S-187S). Among the key recommendations in this chapter are the following: For patients with ischemic symptoms characteristic of acute MI of < 12 h in duration, and ST-segment elevation or left bundle-branch block (of unknown duration) on the ECG, we recommend administration of any approved fibrinolytic agent (Grade 1A). We recommend the use of streptokinase, anistreplase, alteplase, reteplase, or tenecteplase over placebo (all Grade 1A). For patients with symptom duration < 6 h, we recommend the administration of alteplase over streptokinase (Grade 1A). For patients with known allergy or sensitivity to streptokinase, we recommend alteplase, reteplase, or tenecteplase (Grade 1A). For patients with acute posterior MI of < 12 h duration, we suggest fibrinolytic therapy (Grade 2C). In patients with any history of intracranial hemorrhage, closed head trauma, or ischemic stroke within past 3 months, we recommend against administration of fibrinolytic therapy (Grade 1C+). For patients with acute ST-segment elevation MI whether or not they receive fibrinolytic therapy, we recommend aspirin, 160 to 325 mg p.o., at initial evaluation by health-care personnel followed by indefinite therapy, 75 to 162 mg/d p.o. (both Grade 1A). In patients allergic to aspirin, we suggest use of clopidogrel as an alternative therapy to aspirin (Grade 2C). For patients receiving streptokinase, we suggest administration of either i.v. unfractionated heparin (UFH) [Grade 2C] or subcutaneous UFH (Grade 2A). For all patients at high risk of systemic or venous thromboembolism (anterior MI, pump failure, previous embolus, atrial fibrillation, or left ventricular thrombus), we recommend administration of IV UFH while receiving streptokinase (Grade 1C+).

Unequivocal evidence exists that reperfusion therapy, when given within 12 hours after onset of symptoms, saves the lives of patients with acute myocardial infarction (MI). As a result, the routine use of such treatment has increased rapidly since the mid-1980s but the rates of utilisation have been relatively static over the last decade at approximately 50% of patients with acute MI. The major question arising in this respect is: is the benefit of reperfusion therapy, which is achieved during the acute phase in evolving MI, maintained on the long term? The main thrombolytic agents currently in use are streptokinase, alteplase, anistreplase, urokinase and reteplase. Other studies compared coronary angioplasty with thrombolytic therapy and investigated the effect of an additional angioplasty procedure after failed thrombolytic therapy. Furthermore, several studies have been performed to investigate the effect of initiation of reperfusion therapy before hospital admission. It is generally agreed that, in particular, patients receiving early treatment within 6 hours from onset of symptoms and patients with ST elevation benefit most from thrombolytic therapy. One would theoretically expect that infarct size reduction achieved by reperfusion therapy would also have a beneficial effect on the survival, not only during the hospital stay but also afterwards, resulting in diverging survival curves between patients who received reperfusion therapy and those who did not. However, the survival curves run perfectly parallel after hospital discharge from 1 year up to year 10 in most studies. The explanation for a lack of extra benefit may be a net result of combining the results of several subgroups. For example, thrombolytic therapy results in more frequent reinfarction especially in the first year, or patients with low left ventricular ejection fraction could survive the hospital phase because of effective thrombolytic therapy, but they survive at high risk. Although several trials suggest that primary percutaneous transluminal coronary angioplasty may be more beneficial than thrombolytic therapy in acute MI, these data should be interpreted cautiously unless confirmed by larger studies with long term results. In addition, evidence exists to suggest that administration of fibrinolytic treatment, under certain conditions, before hospital admission may lead to further improvement of a patient's prognosis. Again, further investigation is warranted. The conclusion is that clear evidence exists that the early improved survival after thrombolytic therapy has been shown to be maintained beyond a decade. However, the expected theorectical additional benefit of reperfusion therapy after hospital discharge has not been observed.

The treatment of acute myocardial infarction (MI) constitutes a significant problem in remote geographical areas of Greece. Furthermore, thrombolysis, the treatment of choice in the early phase of acute MI, requires the supervision of an expert. We have used thrombolytic treatment, using telemedicine, in remote medical centres. The Onassis Cardiac Surgery Centre was linked to six remote Aegean islands via telemedicine systems which permitted the transmission of 12-lead electrocardiograms (ECGs). The thrombolytic agent anistreplase was administered to patients with acute MI. Supervision, including consultation for treatment of complications, was achieved using the telemedicine system. One hundred and fifty-two ECGs were transmitted during 24 months, of which 108 (71%) indicated specific treatment of a cardiac condition. Ten cases were diagnosed as having acute MI and eight of these were treated with anistreplase. All patients survived acute MI and complications were treated locally. The application of thrombolytic treatment in acute MI is feasible in remote areas, with the use of a telemedicine system.

In patients with acute myocardial infarction (MI), quick initiation of thrombolytic therapy is the best strategy for improvement of survival and reduction of morbidity. Streptokinase, a purified product of haemolytic streptococci, is the most commonly administered agent. The compound anistreplase (a complex of streptokinase to plasminogen), is available but currently not often used. The non-antigenic competitor for these two compounds for the indication of MI is alteplase (recombinant tissue plasminogen activator, rt-PA). Due to former use of streptokinase or its derivative anistreplase, patients may develop specific antibodies to the foreign protein, whereas cross-reacting antibodies may be due to streptococcal infections. These antibodies may neutralise streptokinase or its derivative in case of (re)administration and may mediate adverse events, sometimes serious. Since advanced age by itself is certainly not a contraindication to thrombolytic therapy, and because reinfarction occurs frequently, the benefit-risk ratio of re-exposure to streptokinase or its derivative is decreased in the elderly who present with reinfarction. In the framework of tailored thrombolytic therapy, alteplase or urokinase appear to be the drugs of choice in these patients.

To evaluate the influence of thrombolytic therapy (TT) on the course of acute myocardial infarction (AMI), a comparative analysis of clinical and pathological findings was conducted. The latter included post mortem examination of 35 myocardial samples from patients treated with APSAC in the acute phase of the infarction. The analysis indicated the predominance of cases with unfavourable coronary heart disease, severe myocardial damage and severe AMI complications in the group of the decreased patients. The following beneficial effects of TT were reported: relatively safe stromal and parenchymal myocardial components, earlier regeneration of the connective tissue. Late TT had a negative effect on MI because more hemorrhagic infarctions occurred. The combination of TT and myocardial repair modulators is proposed.

Thrombolytic treatment and aspirin will save about 50 in 1000 patients treated for acute myocardial infarction, but with a risk of cerebral or other serious bleeding in two to three in every 1000. Early treatment (< 4 h) about halves mortality; the benefits decline with time but are clearly proven up to 12 h from onset. Benefit is best and risk least when there is ST elevation and bundle branch (BB) block on the initial ECG. Hypotension is not a contraindication. There is no clear benefit from treatment of patients with ST depression, T wave change or a normal ECG. Streptokinase (SK), tissue plasminogen activator (tPA) or APSAC are equally effective with no mortality benefit for any of the drugs. SK is safer, particularly in older or more hypertensive patients. tPA is reserved for patients who have received SK during the previous year, when high antibody titres may neutralize its effect on a second myocardial infarction (MI). Heparin (either i.v. or high dose S/Q) added to aspirin may confer some small additional benefit, but at the cost of significantly increased risk of bleeding. It should be reserved for high risk patients. Routine angioplasty is unhelpful. Investigation should be reserved for patients with continuing symptoms or ECG evidence of ischaemia, at rest or after stress testing. The benefits of thrombolysis are seen at all ages, in both sexes, and whatever the site of the MI. Aspirin 75-100 mg daily should be continued long-term.

The properties and physiological effects of three currently FDA-approved thrombolytic agents, streptokinase (SK), tissue plasminogen activator (tPA), and anisoylated plasminogen activator complex (APSAC) are reviewed. All thrombolytic agents have been shown to reduce mortality postmyocardial infarction (MI). Comparative trials have failed to demonstrate a difference between the effects of tPA, SK, and APSAC on mortality. In addition, no consistent difference between the three agents on ejection fraction (EF) has been found despite a superior reperfusion rate with tPA at 90 min. Furthermore, reinfarction and interventional procedure rates were significantly higher after thrombolytic treatment, and the incidence of total strokes was higher with tPA than SK in some comparative studies. Based on analysis of the published megatrials, SK is a more cost-effective thrombolytic agent for patients with acute MI than tPA or APSAC.

Streptokinase is well established as an effective thrombolytic. Anistreplase, a new thrombolytic drug, is a complex of streptokinase and acylated human plasminogen that can be administered by intravenous bolus and activates plasminogen at the clot site. Although both streptokinase and anistreplase are effected in treating myocardial infarction (MI), they have different pharmacologic properties. This study was designed to identify short- and long-term differences in their clinical effectiveness, safety in use, and survival rates in patients with acute MI. One hundred ten successive patients under seventy years of age admitted within three hours after onset of sustained chest pain suggestive of acute MI were randomized to receive either 30 units of anistreplase intravenously over five minutes or intravenous injection of 750,000 units of streptokinase over thirty to sixty minutes. Reperfusion was achieved in 34 of the 52 (65%) patients treated with anistreplase and in 41 of the 58 (71%) patients treated with streptokinase (p = NS). The two drugs were equally effective in preserving left ventricular ejection fraction, which was found to be significantly better in patients with anterior wall MI who had achieved reperfusion than it was in those who did not (p less than 0.02). One-month, twelve-month, and thirty-six-month survival rates were high (96% to 88%) with no significant difference between the two treatment groups. The authors conclude that the two drugs are equally effective thrombolytic agents but that anistreplase has the advantage that it can be administered as a bolus injection.

The underlying cause of acute myocardial infarction can now be effectively treated with thrombolytic agents, thereby increasing myocardial salvage and reducing mortality. Clinicians should always be aware of the risk-to-benefit ratio in treating patients with thrombolytic agents and treat each patient on an individual basis.