What is the role of thrombolytics (thrombolytic agents) in the management of myocardial infarction (MI)?

From the Guidelines

Thrombolytics are recommended for patients with ST-elevation myocardial infarction (STEMI) when primary percutaneous coronary intervention (PCI) cannot be performed promptly, as they exert a highly significant 21% proportional reduction in 35-day mortality, corresponding to an overall reduction of 21 deaths per 1000 patients treated 1. The initial evaluation of the patient with suspected acute MI should take place promptly, and the benefit of reperfusion therapy is greatest if therapy is initiated early, ideally within 10 minutes of arrival in the emergency department (ED) 1.

• Key considerations for thrombolytic therapy include:
  • The greatest benefit occurs when thrombolysis is initiated within 6 hours of the onset of symptoms, although it exerts definite benefit when begun within 12 hours 1.
  • Thrombolysis benefits the patient irrespective of age and gender and the presence of comorbid conditions such as diabetes mellitus, although the degree of benefit varies among patient groups 1.
  • Thrombolytic therapy is associated with a slightly increased risk of intracranial hemorrhage (ICH) that usually occurs within the first day of therapy, with variables such as age greater than 65 years, body weight less than 70 kg, systemic arterial hypertension, and administration of tissue plasminogen activator (TPA) predicting an increased risk 1.
• The patient with suspected acute MI should immediately receive oxygen, sublingual nitroglycerin, adequate analgesia, and aspirin, and a 12-lead electrocardiogram (ECG) should be performed to assess for ST-segment elevation, which provides strong evidence of thrombotic coronary arterial occlusion and makes the patient a candidate for immediate reperfusion therapy 1.

From the FDA Drug Label

1.2 Acute Myocardial Infarction Activase is indicated for use in acute myocardial infarction (AMI) for the reduction of mortality and reduction of the incidence of heart failure. The recommended total doses for acute myocardial infarction (AMI) is based on patient weight, not to exceed 100 mg, regardless of the selected administration regimen (accelerated or 3 hour, described below) There are two Activase dose regimens (accelerated and 3-hour) for use in the management of AMI; Accelerated Infusion The recommended accelerated infusion dose consists of an IV bolus [see Dosage and Administration (2.4,2. 5)] followed by an IV infusion as set forth in Table 1. 3-Hour Infusion For patients weighing ≥ 65 kg, the recommended dose is 100 mg administered as 60 mg in the first hour (6-10 mg administered as a bolus), 20 mg over the second hour, and 20 mg over the third hour.

Thrombolytics for MI: The drug label indicates that Activase (which is actually alteplase, not streptokinase) is indicated for use in acute myocardial infarction (AMI) for the reduction of mortality and reduction of the incidence of heart failure.

• The recommended total dose is based on patient weight, not to exceed 100 mg.
• There are two dose regimens: accelerated and 3-hour.
• The choice of regimen depends on patient weight and other factors, as outlined in the tables provided in the drug label 2.

From the Research

Thrombolytics for Myocardial Infarction

• Thrombolytic therapy has been a major advance in the management of acute myocardial infarction, working by lysing infarct artery thrombi and achieving reperfusion, thereby reducing infarct size, preserving left ventricular function, and improving survival 3.
• The most effective thrombolytic regimens achieve angiographic epicardial infarct-artery patency in only approximately 50% of patients within 90 minutes, with bleeding requiring transfusion occurring in approximately 5% of patients and stroke in approximately 1.8% of patients 3.
• Thrombolytic therapy reduces mortality in patients with ST elevation treated within the first 6 to 12 hours of acute infarction, with an approximately 0.5% risk of intracranial haemorrhage 4.
• Newer agents, including tissue plasminogen activators such as alteplase, reteplase, and tenecteplase, have been developed for the treatment of patients with acute myocardial infarction 5.
• Thrombolytic therapy and primary percutaneous coronary intervention have revolutionized the way patients with acute myocardial infarction are managed, resulting in significant reduction in cardiovascular death 5.
• However, in the current era, thrombolytic therapy has been largely supplanted by primary percutaneous coronary intervention as the go-to treatment for acute myocardial infarction, although these agents remain important for vast populations without access to primary PCI and acute ischemic stroke 6.
• The efficacy and safety of low-dose intracoronary alteplase infused early after coronary reperfusion associates with ischemic time, and may be harmful for patients with an ischemic time ≥4 to 6 hours 7.

Benefits and Risks

• Benefits of thrombolytic therapy include reduced infarct size, preserved left ventricular function, and improved survival 3, 4.
• Risks of thrombolytic therapy include bleeding requiring transfusion and stroke 3, 4.
• The risk of intracranial haemorrhage is approximately 0.5% 4.

Current Use

• Thrombolytic therapy is currently used for the treatment of patients with acute myocardial infarction, particularly those without access to primary PCI 6.
• Low-dose intracoronary alteplase may be used as an adjunctive treatment during primary percutaneous coronary intervention, but its use may be harmful for patients with an ischemic time ≥4 to 6 hours 7.