domingo, 29 de agosto de 2010

Should antiplatelet response be tested?

The effectiveness of dual antiplatelet therapy (DAT) with clopidogrel in cardiovascular (CV) patients is highly variable, and the degree of residual platelet aggregation can significantly influence the prognosis. A number of clinical and genetic risk factors contribute to this observation, and the contribution of genetic polymorphisms has been addressed. To date, however, common genetic clusters have not been identified that reliably predict a patient’s response to antiplatelet therapy. The challenge faced by researchers at University Hospital, Tuebingen in Germany is to determine ways of balancing the thrombotic risk, with the risk of bleeding when using DAT. The outcomes of the research includes a conclusion that platelet function testing (PFT), while an important component in risk evaluation, should not be relied on to adjust antiplatelet therapy regimes.
New antiplatelet agents have been developed – and will continue to be developed – that overcome low responsiveness to clopidogrel. These agents have a higher antiplatelet effect and are less susceptible to genetic inheritance. But, according to Professor Meinrad Gawaz of the University Hospital in Tuebingen, Germany, there are important factors to consider before prescribing them. “These new agents offering higher platelet inhibition come with an increased risk of bleeding,” he says. “So far, these drugs have mostly been studied in patients with acute coronary syndromes, but their role in stable CV patients has yet to be fully characterised.”

It is therefore essential to identify sub-groups of patients who could benefit from novel treatment regimes. Platelet function testing (PFT) can help to monitor and guide antiplatelet therapy for patients in at-risk groups more likely to respond to additional antiplatelet therapy. These groups include diabetics and patients suffering from stent thrombosis. Major concerns have been expressed, however, about the transferability of results obtained by different PFT methodologies. Near-patient testing methods have been evaluated in the clinical setting and show reproducible results, but consensus has to be reached upon the appropriate cut-off values to differentiate between thrombotic and bleeding risk.
The results of ongoing trials will show whether adjustment on behalf of routine PFT will lead to improved outcomes. Until then, PFT represents an important component to evaluate the thrombotic risk but adjustment of antiplatelet therapy based on PFT cannot be recommended in a routine fashion but can only be considered as an off-label indication in individual cases bearing in mind the bleeding risk.