Antithrombotic drugs in coronary artery disease: risk benefit ratio and bleeding

The antithrombotic treatment of coronary artery disease is becoming increasingly complex. Aspirin is often combined with more potent antiplatelet agents such as thienopyridines and glycoprotein IIb/IIIa inhibitors. The classic anticoagulant unfractionated heparin is giving way to low-molecular-weight heparin, the pentasaccharide fondaparinux and the direct thrombin inhibitor bivalirudin. Warfarin (or another vitamin K antagonist) and antiplatelet agents are often required in combination for several months. Patients and physicians who have experienced major bleeding complications sometimes question the benefit of these treatment strategies. It is therefore crucial to try and weigh the impact on efficacy against safety. In this review the net benefit is discussed both numerically, comparing absolute reductions vs. increases in risks, and also by addressing the qualitative importance of each component in reaching the net benefit. Except for primary prophylaxis in patients at low-moderate risk for coronary events, there is a net benefit of antithrombotic therapy. With increasing severity of the coronary condition the net benefit generally prevails even with an increasing number of antithrombotic drugs combined. However, as the patient slowly stabilizes after appropriate interventions, it is necessary to de-escalate the treatment in accordance with decreasing net benefit of prolonged combination therapy.