Adjunctive Anti-thrombotic Therapy
The various types of adjunctive anti-thrombotic therapies are as listed below:
Aspirin
Aspirin irreversibly acetylates platelet cyclooxygenase and therefore inhibits platelet aggregation; it is also an indirect antithrombotic agent. Aspirin is the most cost-effective treatment available for patients with AMI (indeed, with any ACS) and should be administered early in all patients with ischaemic cardiac chest pain who do not have a known allergy or active gastro-intestinal bleeding. Offer people with acute STEMI a single loading dose of 300-mg aspirin as soon as possible unless there is clear evidence that they are allergic to it [22].
Learning Bite
Aspirin is the most cost-effective treatment for AMI, and is associated with a survival benefit similar to thrombolysis.
Clopidogrel
Clopidogrel is also an anti-platelet agent; it promotes formation of platelet c-AMP, lowering platelet calcium and reducing platelet aggregation. It also prevents the transformation of the glycoprotein IIB/IIIA receptor into its high affinity state, further reducing platelet aggregation. Two recent trials have reported the beneficial effects of clopidogrel in patients with STEMI: patients receiving clopidogrel, in addition to thrombolysis, aspirin and heparin, had a significantly reduced incidence of adverse events at 30 days [15-16].
NICE [22] advises to offer Clopidogrel, as part of dual antiplatelet therapy with aspirin, if they are already taking an oral anticoagulant. For people with acute STEMI not treated with PCI, consider clopidogrel, as part of dual antiplatelet therapy with aspirin, or aspirin alone, if the patients have a high bleeding risk [22].
Prasugrel
Prasugrel is, like clopidogrel, an oral anti-platelet agent and acts in a similar way to clopidogrel but with a faster onset of action. NICE [22] recommends to use Prasugrel in patients with STEMI undergoing PPCI, as part of dual antiplatelet therapy with aspirin, if they are not already taking an oral anticoagulant (for patients aged 75 and over, think about whether the person’s risk of bleeding with prasugrel outweighs its effectiveness, in which case offer ticagrelor or clopidogrel as alternatives).
Learning bite
Prasugrel has become the preferred option over clopidogrel in patients receiving PPCI for STEMI.
Ticagrelor
Ticagrelor is another novel oral anti-platelet agent, which is an antagonist to the P2Y12 ADP receptor and, co-administered with aspirin, is indicated in the management of patients with acute coronary syndromes. It has undergone a NICE Technology Appraisal which has recommended its’ use in combination with aspirin as an alternative to clopidogrel in patients with STEMI undergoing PPCI [18]. Ticagrelor is being increasingly adopted instead of clopidogrel in STEMI patients undergoing PPCI, who are unsuitable for prasugrel.
NICE [22] advises to offer ticagrelor, as part of dual antiplatelet therapy with aspirin, to patients with acute STEMI not treated with PCI, unless they have a high bleeding risk.
Heparin
Unfractionated heparin (UH) inhibits clot formation by preventing the conversion of fibrinogen to fibrin. Low Molecular Weight Heparins (LMWH) inhibit the coagulation system in a similar way and also bind to Factor Xa which is resistant to inactivation by UH. LMWH also has a longer half-life, less individual variability of the anticoagulant response, more predictable kinetics and less platelet activation than UH. These agents do not enhance immediate clot lysis, but prevent re-occlusion following thrombolysis.
A recent direct comparison of UH and the LMWH enoxaparin in patients with STEMI receiving in-hospital thrombolysis reported improved outcome at 30 days in the enoxaparin group [19]. Indeed, one of the lowest 30 day mortality rates of recent trials (5.4%) was reported using the combination of thrombolysis and enoxaparin [20]. However, there have been concerns of increased intracranial haemorrhage in the elderly with this regime used in the pre-hospital setting.
With the increased use of PPCI and the emergence of the newer anti-thrombotic agents discussed above, heparins are used much less frequently as anti-thrombotic agents in the initial management of STEMI.
Fondaparinux
Fondaparinux is a selective Factor Xa Inhibitor that has recently been evaluated in the setting of STEMI: it was found to be associated with reduced mortality and reduced re-infarction when compared to UH or placebo [21]. It is indicated in patients who are managed initially with thrombolytics or who have no specific reperfusion therapy. It is not indicated in patients undergoing PPCI. It has a long half-life and is given once daily.
Glycoprotein IIB/IIIA inhibitors
Clinical studies have not reported improved outcome with GpIIB/IIIA Inhibitors agents as adjuvant therapy with thrombolysis in the setting of STEMI and there is, therefore, no role for GpIIB/IIIA Inhibitors in this context in routine clinical practice [20].