Current guidelines support dual antiplatelet therapy with aspirin and clopidogrel (Plavix) in a number of clinical scenarios:
- ST-segment-elevation myocardial infarction (SEMI),
- Non-ST-elevation MI,
- Percutaneous Coronary Intervention.
The guidelines are based on strong evidence from several large randomized clinical trials over the last 10 years.
- Dual antiplatelet therapy is recommended after ST-elevation MI or non-ST-elevation acute coronary syndromes, with aspirin indefinitely and clopidogrel for up to 1 year.
- Dual antiplatelet therapy is recommended for at least 1 month after placement of a bare-metal stent and for at least 1 year (or possibly indefinitely) after placement of a drug-eluting stent.
- There is no compelling indication for clopidogrel in patients with chronic coronary artery disease.
The most important antiplatelet drugs are:
- Cyclooxygenase inhibitors
- Adenosine diphosphate (ADP) receptor inhibitors
- Phosphodiesterase inhibitors
- Cilostazol (Pletal)
- Glycoprotein IIB/IIIA inhibitors(intravenous use only)
- Adenosine reuptake inhibitors
- Dipyridamole (Persantine)
Prevention and treatment of arterial thrombosis
Treatment of established arterial thrombosis includes the use of Antiplatelet drugs and thrombolytic therapy. Antiplatelet drugs alter the platelet activation at the site of vascular damage crucial to the development of arterial thrombosis.
- Aspirin irreversibly inhibits the enzyme COX, resulting in reduced platelet production of TXA2 (thromboxane – powerful vasoconstrictor which lowers cyclic AMP and initiates the platelet release reaction).
- Dipyridamole inhibits platelet phosphodiesterase, causing an increase in cyclic AMP with potentiation of the action of PGI2 – opposes actions of TXA2
- Clopidogrel affects the ADP-dependent activation of IIb/IIIa complex
- Glycoprotein IIb/IIIa receptor antagonistsblock a receptor on the platelet for fibrinogen and von Willebrand factor. 3 classes:
- Murine-human chimeric antibodies (e.g. abciximab)
- Synthetic peptides (e.g. eptifibatide)
- Synthetic non-peptides (e.g. tirofiban)
- Epoprostenol is a prostacyclin which is used to inhibit platelet aggregation during renal dialysis (with or without heparin) and is also used in primary pulmonary hypertension.
Thrombolytic therapy is used in myocardial infarction, cerebral infarction and occasionally in massive pulmonary embolism. The main risk is bleeding. Treatment should not be given to patients who have had recent bleeding, uncontrolled hypertension or a hemorrhagic stroke, or surgery or other invasive procedures within the previous 10 days.
- Streptokinase forms a complex with plasminogen, resulting in a conformational change which activates other plasminogen molecules to form plasmin.
- Plasminogen activators (PA), tissue-type plasminogen activators (alteplase, tenecteplase) are produced by recombinant technology.