Thrombolysis for Acute Myocardial Infarction

Abstract

Thrombolytic therapy has been a major advance in the management of acute myocardial infarction. Unfortunately, it continues to be underused or is administered later than is optimal. Thrombolytic therapy works by lysing infarct artery thrombi and achieving reperfusion, thereby reducing infarct size, preserving left ventricular function, and improving survival. The most effective thrombolytic regimens achieve angiographic epicardial infarct-artery patency in only approximately 50% of patients within 90 minutes. Bleeding requiring transfusion occurs in approximately 5% of patients and stroke in approximately 1.8% with these regimens, which include adjunctive aspirin and intravenous heparin. There are several ways in which reperfusion rates and thus patient outcomes might be improved, such as different dosing regimens of established agents; combinations of different agents; improved adjunctive therapy such as direct antithrombin agents, low-molecular-weight heparin, or glycoprotein IIb/IIIa receptor antagonists; or the development of novel thrombolytic agents with enhanced fibrin specificity, resistance to native inhibitors, or prolonged half-lives allowing bolus administration. All of these strategies are being tested in clinical trials. The best approach currently is to administer thrombolytic therapy as soon as possible to all patients without contraindications who present within 12 hours of symptom onset and have ST-segment elevation on the ECG or new-onset left bundle-branch block, unless an alternative reperfusion strategy is planned.

Fibrinolysis for Acute Myocardial Infarction

“…Deletion of the fingerlike domain contributes to lesser fibrin specificity. 1,43 A phase 2 study of nPA, Intravenous nPA for Infarcting Myocardium Early (InTIME), evaluated nPA administered as a split, single bolus over 2 to 4 minutes in doses varying between 15 and 120 kU/kg compared with accelerated rt-PA. 43 Although a clear dose response on 60-minute TIMI 3 patency was evident over the first 3 doses, no incremental patency advantage was evident between 60 and 120 kU/kg, and neither of the 2 top doses exceeded that achieved with rt-PA. The 120-kU/kg dose was subsequently chosen for a large phase 3 comparative study (InTIME-2) with a 2-to-1 randomization of nPA compared with accelerated rt-PA. 44 Although the 30-day mortality rates for nPA (6.77%) and rt-PA (6.60%) were similar, there was an unacceptable excess of intracranial hemorrhage with nPA (1.13% versus 0.62%, Pϭ0.003) and an increase in the composite of mild and moderate bleeding with nPA (22% versus 17%, Pϭ0.0001).…”

“…1 Although streptokinase (SK), recombinant tissue plasminogen activator (rt-PA), and more recently reteplase (r-PA) are in general clinical use, there remains some dissatisfaction with their overall efficacy. This relates in part to the failure to achieve optimal tissue reperfusion in approximately one half of patients so treated, as well as persistent risks associated with systemic hemorrhagic effects, some of which complicate ancillary vascular interventional procedures in complicated patients.…”

Cardiac surgery and hypertension: a dangerous association that must be well known

“…Thrombolytic therapy is the optimal choice for patients with acute myocardial infarction within 12 hours after the onset of the symptoms [68]. The principle of treatment choices for either percutenous transluminal coronary angioplasty or coronary artery bypass grafting will be guided by technical improvements in cardiology or surgery, local expertise, and patients preference.…”

Xylarinase: a novel clot busting enzyme from an endophytic fungusXylaria curta

“…Heart related diseases such as myocardial infarction 4 , high blood pressure; ischemic heart diseases 5 are primarily caused due to accumulation of fibrin in the walls of the blood vessels resulting in the formation of a haemostatic plug or a clot 6 . In such conditions, drugs like urokinase and streptokinase are administrated intravenously to dissolve the fibrin clots 7 .…”