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29 August 2010

Assessing the risks of bleeding from antithrombotic therapy


Antithrombotic therapy using antiplatelet and anticoagulant agents is the cornerstone of treatment for acute and chronic coronary artery disease (CAD), yet it is also associated with an increased risk of bleeding. It is paradoxical that elderly patients, the most likely population to develop CAD, are those that suffer most from bleeding complications. Research has been carried out at OLVG Hospital in the Netherlands into the stratification of risk for all patients requiring this type of therapy.
Professor Freek Verheugt led the research. “Until relatively recently, aspirin used to be the only effective antiplatelet drug, but now CAD patients can get increased protection from ADP receptor antagonists added to aspirin,” he said. “Previous studies showed us that, compared to younger patients, the elderly seemed to benefit more from single antiplatelet therapy with aspirin that from dual antiplatelet therapy. This data, however, should be treated with caution since it is derived from post-hoc analysis of randomised control trials.”
The TRITON and PLATO clinical trials demonstrated that newer ADP blockers such as prasugrel and ticagrelor are more effective that clopidogrel. But in both trials, the benefits seemed to reduce in patients over 75 years, although this observation comes from post-hoc analyses of the mega-trials. Other research has also shown that the elderly do not get the full benefit from platelet glycoprotein IIb/IIIa receptors, include abciximab, eptifibatide and tirofiban.
For anticoagulants, there is less data available on the risk of bleeding in relation to age. In elderly patients with fibrinolysis, low molecular weight heparin increases the bleeding risk in the elderly significantly over un-fractionated heparin. So, if chosen as the most effective treatment, low molecular weight heparin should be administered in lower doses for older patients. Bleeding associated with the newer anticoagulant bivalirudin also increased in the elderly, when compared to younger patients.
The research concludes that the risk of bleeding is increased by antiplatelet and anticoagulant therapy when applied to the treatment of acute and chronic CAD. Professor Verheugt explained the findings, “For aspirin, it was clearly shown that the risk reduction of ischemic endpoints applies equally to the elderly, but for clopidogrel this benefit is less apparent. Neither was it clearly seen from use of newer ADP receptor blockers such as prasugrel and ticagrelor. Additionally, no clear benefit was observed for elderly patients treated with glycoprotein receptor blockers for acute coronary syndromes.”
Antiplatelet therapies carry an increased risk of bleeding, especially in the elderly. This is probably also true for anticoagulant drugs, but data that specifically covers the elderly is relatively scarce.

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