Thrombolytic therapy myocardial infarction

Thrombolytic Enzymes. Although atherosclerosis and the accompanying vascular wall defects are ultimately responsible for such diseases as acute pulmonary embolism, arterial occlusion, and myocardial infarction, the lack of blood flow caused by a fibrin clot directly results in tissue injury and in the clinical symptoms of these devastating diseases (54). Thrombolytic enzyme therapy removes the fibrin clot by dissolution, and has shown promise in the treatment of a number of thrombo-occlusive diseases (60). 

Krumholz HM, Pasternak RC, Weinstein MC, et al. Cost effectiveness of thrombolytic therapy with streptokinase in elderly patients with suspected acute myocardial infarction. N Engl J Med 1992 327 7-13. 

Alteplase has proven effective in the early treatment of patients with acute myocardial infarction (i.e. those treated within 12 h after the first symptoms occur). Significantly increased rates of patient survival (as measured 1 day and 30 days after the initial event) are noted when tPA is administered in favour of streptokinase, a standard therapy (see later). tPA has thus established itself as a first-line option in the management of acute myocardial infarction. A therapeutic dose of 90-100 mg (often administered by infusion over 90 min) results in a steady-state alteplase concentration of 3-4 mg l 1 during that period. However, the product is cleared rapidly by the liver, displaying a serum half-life of approximately 3 min. As is the case for most thrombolytic agents, the most significant risk associated with tPA administration is the possible induction of severe haemorrhage. 

Castillo, P.A., Palmer, C.S., Halpern, M.T., Hatziandreu, E.J., and Gersh, B.J. 1997. Cost-effectiveness of thrombolytic therapy for acute myocardial infarction. Annals of Pharmacotherapy 31(5), 596-603. 

Hegele (H23) reported an acute reduction of Lp(a) during tPA infusion. The success of this type of thrombolytic therapy for acute myocardial infarction seems to be unaffected by high Lp(a) levels (H32). 

H32. Hodenberg, E. von, and Kreuzer, J., Effects of lipoprotein(a) on success rate of thrombolytic therapy in acute myocardial infarction. Am. J. Cardiol. 67, 1349-1353 (1991). 

Franzosi MG, Santoro E, De Vita C, et al. Ten-year follow-up of the first megatrial testing thrombolytic therapy in patients with acute myocardial infarction results of the Gruppo Italiano per lo Studio della Sopravvivenza nellTnfarto-l study. The GISSI Investigators. Circulation 1998 98 2659-2665. 

O Keefe JH, Jr., Rutherford BD, McConahay DR, et al. Early and late results of coronary angioplasty without antecedent thrombolytic therapy for acute myocardial infarction. Am J Cardiol 1989 64 1221-1230. 

Grines CL, Browne KF, Oneil W, et al., for the Primary Angioplasty in Myocardial Infarction study group. A comparison of immediate angioplasty with thrombolytic therapy for acute myocardial infarction. N Engl J Med 1993 328 673-679. 

Collen, D. (1998). Staphylokinase a potent, uniquely fibrin-selective thrombolytic agent. Nature Med. 4(3), 279-284. Collins, R. et al. (1997). Drug therapy—aspirin, heparin and fibrinolytic therapy in suspected acute myocardial infarction. N. Engl. J. Med. 336(12), 847-860. 

E Role in therapy Thrombolytic agents currently licensed for the treatment of AMI in the United States include streptokinase, tissue plasminogen activator, anistreplase, reteplase, and tenecteplase. TNKase and alteplase have similar clinical efficacy for thrombolysis after myocardial infarction (i.e., similar mortality and intracranial hemorrhage rates). However, advantages of TNKase include ease and rapidity of administration, longer half-life, greater fibrin specificity, and lower noncerebral bleeding rates. Reteplase shares some characteristics of tenecteplase (e.g., similar half-life, rapid onset, and ease of administration). 

The paradigm shift in 1980 on the causation of acute myocardial infarction to acute coronary occlusion by a thrombus created the rationale for thrombolytic therapy of this common lethal disease. At that time—and for the first time-intravenous thrombolytic therapy for acute myocardial infarction in the European Cooperative Study Group trial was found to reduce mortality significantly. Later studies, with thousands of patients in each trial, provided enough statistical power for the 20% reduction in mortality to be considered statistically significant. Although the standard of care in areas with adequate facilities and experience in percutaneous coronary intervention (PCI) now favors catheterization and placement of a stent, thrombolytic therapy is still very important where PCI is not readily available. 

The proper selection of patients for thrombolytic therapy is critical. The diagnosis of acute myocardial infarction is made clinically and is confirmed by electrocardiography. Patients with ST-segment elevation and bundle branch block on electrocardiography have the best outcomes. All trials to date show the greatest benefit for thrombolytic therapy when it is given early, within 6 hours after symptomatic onset of acute myocardial infarction. 

Clinical use Acetylsalicylic acid is the prototype of a nonsteroidal anti-inflammatory drug and is used in a large number of inflammatory and pain indications including musculoskeletal, soft tissue and joint disorders, headache, dysmenorrhoea and fever (Symposium on new perspectives on aspirin therapy 1983, various authors). Furthermore, acetylsalicylic acid is used as an antiplatelet drug in the acute treatment of myocardial infarction in combination with thrombolytics and for the prevention of myocardial infarction and stroke (Patrono, 1994). 

Myocardial infarction -thrombolytic therapy [ENZYME APPLICATIONS - THERAPEUTIC] (Vol 9)... 

Two women and one man, aged 53-74 years, died after they received thrombolytic therapy for acute myocardial infarction. All three had a long history of seropositive rheumatoid arthritis treated with prednisone 5-20 mg/day for many years. 

Kotha P, McGreevy MJ, Kotha A, Look M, Weisman MH. Early deaths with thrombolytic therapy for acute myocardial infarction in corticosteroid-dependent rheumatoid arthritis. Clin Cardiol 1998 21(ll) 853-6. 

Thrombolytic drugs (streptokinase, t-PA, others) usually do not have a direct impact on physical therapy or occupational therapy. Thrombolytics are typically given in acute situations, immediately following myocardial infarction. Therapists may, however, benefit indirectly from the effects of these drugs because patients may recover faster and more completely from heart attacks. Thrombolytics may also help reopen occluded peripheral vessels, thus improving tissue perfusion and wound healing in rehabilitation patients. 

Menon V, Harrington RA, Hochman JS, et al. Thrombolysis and adjunctive therapy in acute myocardial infarction the Seventh ACCP Conference on Antithrombotic and Thrombolytic Therapy. Chest. 2004 126(suppl) 549S-5 75 S. 

All patients with acute myocardial infarction should be considered for intravenous thrombolytic therapy with streptokinase, tissue plasminogen activator (TPA), or anistreplase because these agents are effective in both preserving cardiac function and reducing mortality. 

Thrombolytic therapy in the management of acute myocardial infarction requires careful patient selection, the use of a specific thrombolytic agent, and the benefit of adjuvant therapy. Considerable controversy surrounds the question of greater safety or efficacy of t-PA compared with the other thrombolytic agents (see Thrombolytic Drugs for Acute Myocardial Infarction). 

These agents have been tested in various conditions where platelet activation plays a major role, in particular in patients undergoing percutaneous coronary intervention (PCI), patients admitted with ACS, and patients receiving thrombolytic therapy for acute myocardial infarction (Ml) (Fig. 2). 

Cannon CP Overcoming thrombolytic resistance. Rationale and initial clinical experience combining thrombolytic therapy and glycoprotein llb/llla receptor inhibition for acute myocardial infarction. J Am Coll Cardiol 1999 34 1395. 

Argatroban as adjunctive therapy to thrombolytics in acute myocardial infarction... 

Scharfstein JS, Abendschein DR, Eisenberg PR, et al. Usefulness offibrinogenolytic and procoagulant markers during thrombolytic therapy in predicting clinical outcomes in acute myocardial infarction. TIMI-5 Investigators. Thrombolysis in myocardial infarction. Am J Cardiol 1996 78 503-510. 

The clear alternative to fibrinolytic therapy in the reperfusion strategy of ST-segment elevation acute myocardial infarction is primary coronary angioplasty. This therapy has a clinical benefit over the optimal thrombolytic strategy front-loaded rt-PA or tenecteplase (13). The major drawback of primary angioplasty is its limited availability and treatment delay. The... 

Boersma E, Maas AC, Deckers JW, Simoons ML. Early thrombolytic therapy in acute myocardial infarction reappraisal of the golden hour. Lancet 1996 348 771-775. 

---