Overview

Metalyse® (tenecteplase) is a thrombolytic agent indicated for the thrombolytic treatment of suspected myocardial infarction with persistent ST elevation or recent left bundle branch block; its use is limited to within 6 hours after the onset of symptoms of acute myocardial infarction.  

 

The use of Metalyse® is now established as a major advance in the management of acute myocardial infarction, and can give a 12-50% reduction in short-term mortality, and up to 47% in long-term mortality.

Thrombolytics activate the natural endogenous lytic pathways in the circulation, and dissolve blood clots. The precursor of this pathway is plasminogen, which is converted into the active enzyme plasmin. Plasmin is a protease enzyme (i.e. it breaks down proteins) which breaks down the fibrin matrix of the thrombus, thus dissolving the clot itself. Thrombolytics have no effect on the underlying atheromatous disease.

Plasmin is non-specific and can attack other proteins including fibrinogen, the precursor to fibrin. This may increase the risk of bleeding as it can dissolve other clots in the body, and prevent new clotting taking place.

Alteplase and its derivatives (for example, reteplase and tenecteplase) are more specific than streptokinase, targeting plasminogen in the presence of a fibrin clot as opposed to circulating fibrinogen. Therefore, these agents attain higher early patency rates. Heparin inhibits clotting by affecting fibrin formation and modifying platelet aggregation. A better clinical effect, notably improved angiographic patency, has been achieved in studies when thrombolytics have been administered in conjunction with heparin.

Given early enough, thrombolytic treatment will remove the thrombus, re-establish the blood flow, limit myocardial damage and consequently improve prognosis by preserving left ventricular function.

Principle of Lysis

Pharmacological reperfusion: Components of the fibrinolytic system

Pharmacological reperfusion Components of  the fibrinolytic system Diagram showing different components of the fibrinolytic system and their regulatory affects

Recanalisation is the process of reopening a blocked artery to allow blood to flow through it. Patency is the state of being wide open. Therefore recanalisation restores the patency of the blocked artery and thus allows resumption of blood flow through this artery. The goal of thrombolysis is recanalisation.

Restoring the patency of a coronary blood vessel, and reintroducing blood flow to the tissue, enables reperfusion. The flow of blood and oxygen to the muscle halts anaerobic respiration, and therefore cell death. It is not possible to reverse cell death, but by restoring the blood flow and availability of oxygen, jeopardised muscle can be salvaged. This preserves the left ventricular function, increasing survival.

Early reperfusion:

  • prompt relief of pain,
  • reduction in ST elevation.

Late reperfusion:

  • less likely to produce resolution of ECG,
  • reduced mortality,
  • improved morbidity.

Thrombolysis has been shown to significantly reduce the risk of mortality for patients suffering an acute myocardial infarction. Early treatment (within 2 hours of symptom onset) is especially beneficial, with large reductions in risk of mortality. Reperfusion usually occurs within 1 hour of thrombolysis. This results in the prompt relief of pain and a reduction in the ST elevation, which can be seen on the ECG. However, late reperfusion due to delayed administration of a thrombolytic or a slow acting thrombolytic is less likely to produce resolution of the ECG changes. It is quite common to get reperfusion arrhythmias due to atrial or ventricular ectopics, but they are usually short-lived and rarely require treatment. Early treatment can therefore minimise the damage to the myocardium, salvaging some muscle. This results in improvements in left ventricular function, increasing both short-term and long-term survival.

References: 
  1. Cannon et al. Circulation 1998; 98 (25): 2805–2814.
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