Safety of antithrombotic treatment in acute coronary syndromes

The management of acute coronary syndromes (with or without ST segment elevation) requires the use of anticoagulants, antiplatelet agents (aspirin, clopidogrel and/or glycoprotein (GP) IIb/IIIa inhibitors), beta-blockers, thrombolytics in some cases, and revascularization / reperfusion.

The appropriate management of ACS has been shown over the last few decades to result in a significant improvement in outcome in the short and long term. However, the combined use of these therapies, particularly antithrombotic therapies (which include anticoagulants, antiplatelet agents and thrombolytics) may result in an excess of bleeding. Until the recent past, bleeding was not considered to be a serious complication, but over the last 5 years, bleeding complications have in fact emerged as a major contributor to overall risk, with a significant increase in the rate of death, myocardial infarction and stroke in patients who suffer bleeding complications during the initial phase of ACS, as compared to those who do not. In addition, blood transfusion has been shown to result in a higher risk of death, and is suspected to have deleterious effects in selected groups of patients.

The risk factors for bleeding have been well identified. Older age, female sex and low body weight have been identified as markers of the risk of bleeding. A past history of bleeding, the presence of renal failure, the use of an early invasive approach, excess dose of antithrombotic agents, and use of GP IIb/IIIa inhibitors have also been identified as strong predictors of the risk of bleeding.

Conversely, careful selection of drugs, giving precedence to drugs with less potential for bleeding, use of a radial versus femoral approach for invasive strategy, and systematic use of proton pump inhibitors to avoid gastro-intestinal bleeding during the initial phase, are all measures that have the potential to reduce the bleeding risk.

In this context, some anticoagulants have been shown to carry a lower risk of bleeding, such as fondaparinux and bivalirudin, as compared to low molecular weight heparins or unfractionated heparin. It would also appear that more consistent inhibition of platelet aggregation leads to better clinical outcome, albeit with an increased risk of bleeding.

In all, bleeding and possibly also blood transfusion have emerged as major contributors to worse outcome in patients with ACS. Proper management of patients, with appropriate selection of doses, drugs, and arterial approach, combined with systematic evaluation of the bleeding risk prior to starting therapy may help prevent bleeding and improve patient outcome.