Medical management of unstable angina

Medical management of unstable angina

Initial medical management of unstable angina includes: restriction activities, morphine for pain relief, oxygen supplementation if there is hypoxia, nitroglycerine for pain relief, prevention of silent ischemia, control of hypertension and relief of ventricular dysfunction. Nitrate free period is recommended after first 24-48 hours of use of nitroglycerine, to prevent tolerance.

Beta-blockers lower anginal threshold and prevent ischemia and death after myocardial infarction. They are particularly useful during high sympathetic tone. Calcium antagonists, particularly the rate-limiting agents like verapamil and diltiazem are useful in unstable angina. Nifedipine is not recommended without concomitant beta blockade as it can cause hypotension and reflex tachycardia if used as monotherapy.

Thrombolytics agents are not indicated in unstable angina. Lytic agents may stimulate the thrombogenic process and result in paradoxical aggravation of ischemia and myocardial infarction.
Platelets play a key role in acute coronary syndrome. Sources of platelet activation (triggers) include thromboxane A2 (TXA2), ADP, epinephrine, exposed collagen in the vessel wall and thrombin.
Aspirin was the “gold standard” for antiplatelet therapy in unstable angina. It produces irreversible inhibition of COX pathway in platelets, blocking formation of TX A2 and platelet aggregation. In acute myocardial infarction, aspirin reduced risk of death by 20-25%, while in unstable angina it reduced the risk of myocardial infarction by 71%. Loading dose of 160~325 mg, followed by maintenance dose of 80~160 mg/day are required.

GP IIb/IIIa receptor is the final pathway to platelet aggregation. Platelet activation and aggregation are early events in development of coronary thrombosis. GP IIb/IIIa receptors on activated platelets undergo a conformational change allowing binding of fibrinogen. Fibrinogen bridges GP IIb/IIIa receptors on adjacent platelets, leading to platelet aggregation.

Thienopyridines like ticlopidine and clopidogrel block platelet aggregation induced by ADP and the transformation of GP IIb/IIIa into its high affinity state. Ticagrelor is more effective but costlier.

GP IIb/IIIa inhibitors include abciximab (monoclonal antibody), eptifibatide (peptidic inhibitor) and tirofiban (non-peptides). Direct occupancy of the GP IIb/IIIa receptor by monoclonal antibody or by synthetic compounds mimicking the RGD (Arg-Gly-Asp) sequence for fibrinogen binding prevents platelet aggregation. These agents are seldom used for medical management.

Heparin, low molecular weight heparin and fondaparinux are also important in the treatment of unstable angina.

Refractory cases have to be considered for early invasive strategy.