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Heart Attack Treatment

The Future of Heart Attack Treatment The introduction of thrombolytics in the late 1980's revolutionized the treatment of heart attack, or acute myocardial infarction (AMI). Thrombolytics work by dissolving a clot that blocks a coronary artery and restoring blood flow to the heart.

  • In 1987, the U.S. Food and Drug Administration (FDA) approved two thrombolytics, streptokinase (Streptase®) and t-PA (Activase®; Alteplase, recombinant) for the treatment of heart attack, both which caused a substantial decrease in death and disability in patients who received them.
  • Results of the landmark GUSTO-1 (Global Utilization of Streptokinase and Tissue Plasminogen Activator for Occluded Coronary Arteries) study found that Activase reduced mortality by 14 percent and saved one additional life per 100 patients, compared to streptokinase (Kabikinase®).

To move beyond current standards of heart attack treatment, researchers currently are focused on identifying:

  • Better thrombolytic agents
  • Better adjunctive agents
  • Mechanical interventions

Thrombolytic agents are looking to combine the best features of the most widely used agent during the past decade, Activase, with the added benefit of faster administration. Key benefits include: a prolonged half-life (which allows single-bolus administration), a high level of fibrin specificity and resistance to plasminogen activator inhibitor (PAI-1).

  • A thrombolytic agent is TNKase® (Tenecteplase), approved by the FDA for the treatment of heart attack. TNKase can be administered over five seconds and in a single dose. As with all thrombolytics, the most significant adverse events observed in clinical trials with TNKase included intracranial hemorrhage and stroke.
  • All thrombolytic agents increase the risk of bleeding, including intracranial bleeding, and should be used only in eligible patients. In addition, thrombolytic therapy increases the risk of stroke, including hemorrhagic stroke, in elderly patients.
  • Mechanical interventions

Aspirin and heparin have been used for the past several years as adjuncts for heart attack treatment. Now, newer adjunctive agents are being investigated.

With the introduction of newer thrombolytics and newer adjunctive agents, several combination regimens using a thrombolytic with leading anti-thrombotic agents now are being tested.

  • One of the larger combination therapy trials, ASSENT 3, evaluated the safety and efficacy of TNKase and current anti-thrombotics in three combination regimens: full-dose TNKase plus Aventis' low molecular weight Lovenox (enoxaparin), half-dose TNKase plus unfractionated heparin plus Centocor's glycoprotein IIb/IIIa inhibitor ReoPro (abciximab), and full-dose TNKase plus unfractionated heparin.
  • All thrombolytic agents increase the risk of bleeding, including intracranial bleeding, and should be used only in eligible patients. In addition, thrombolytic therapy increases the risk of stroke, including hemorrhagic stroke, in elderly patients.

Mechanical interventions involve the use of angioplasty or stents.

  • Angioplasty involves the insertion and inflation of a balloon into a blocked blood vessel to expand the artery. An advantage to angioplasty is that it can open most blocked arteries, but it requires 24-hour availability of catheterization laboratories and highly trained interventional cardiologists. While results of trials comparing thrombolytics to angioplasty differ, a recent study found that these two treatment modalities may someday be used in a complementary way.
  • Stents are tiny cylindrical scaffolds that prop open coronary arteries. Physicians believed that stenting would be helpful in patients who experience vessel renarrowing, which often occurs within six months of an angioplasty procedure.

Sources ASSENT 2 (ASsessment of the Safety and Efficacy of a New Thrombolytic) Investigators. Single-bolus thrombolytic compared with front-loaded alteplase in acute myocardial infarction: The ASSENT 2 double-blind randomized trial. Lancet 1999; 354: 716-22.

Grines CL, Cox DA, Stone GW, et al. Coronary Angioplasty with or without Stent Implantation for Acute Myocardial Infarction. N Engl J Med 1999; 341: 1949-56.

GUSTO 1 (Global Utilization of Streptokinase and Tissue Plasminogen Activator for Occluded Coronary Arteries) Investigators. An International Randomized Trial Comparing Four Thrombolytic Strategies for Acute Myocardial Infarction. N Engl J Med 1993; 329: 673-82.

GUSTO IIb Angioplasty Substudy Investigators. A Clinical Trial Comparing Primary Coronary Angioplasty with Tissue Plasminogen Activator for Acute Myocardial Infarction. N Engl J Med 1997; 336: 1621-8.