What's new about clopidogrel.

Clopidogrel is an oral tyenopiridin with a central role in the management of acute coronary syndromes and after stent implantation. Despite the use of this drug, many patients continue to experience thrombotic events which are usually referred as "therapy failure". Actually, to date, only stent thrombosis is considered therapy failure: mainly, it could be due to patient genetic predisposition or drug interaction, in particular with proton pump inhibitors. Genetic mutations in the CYP2C19 cytochrome (involved in the metabolism of clopidogrel and many other drugs) may lead to a lower concentration of active metabolites of the drug. In the same way, proton pump inhibitors interaction with the cytochrome may reduce clopidogrel activation. To overcome the problem some authors have suggested to increase the dosage of the drug, to use other drugs, to genotype patients, and not to use proton pomp inhibitors in patients on double antiplatelet therapy. Recent studies have shown that the interaction between clopidogrel and proton pump inhibitors is far to be clinically relevant and that the variability between the different assay to determine patients response to the drug does not allow, to date, to rely on their use. Moreover, double clopidogrel dose is as effective as low one in preventing major cardiovascular events, with a significant reduction in stent thrombosis in spite of a modest increase in major bleeding. Aim of this review article was to update current knowledge on clopidogrel, particularly focusing on the problem of "resistance" and PPI interaction. Moreover, we will discuss current strategies to overcome the resistance.

[Ranolazine in the treatment of chronic stable angina]. / La Ranolazina nella terapia della angina cronica stabile.

Coronary artery disease is the leading cause of death in Europe and in the US and angina is the most common symptom associated with stable coronary artery disease. Despite receiving optimal antianginal therapy, based on agents such as beta-blockers, calcium channel antagonists and nitrates, many patients continue to experience angina. Furthermore, the administration of these drugs is limited by adverse effects such as bradycardia or hypotension. Ranolazine is a new antianginal agent, recently approved as add-on therapy in patients with stable angina. This review will focus on its mechanism of action, tolerability, highlighting the clinical benefit coming from its use.

[High-sensitivity troponin assay: biochemistry and clinical application]. / Troponine ad alta sensibilita: dalla biochimica alle applicazioni cliniche.

Cardiac troponin is the marker of choice for the diagnosis of acute coronary syndrome. Its introduction in clinical practice consistently improved both sensibility and specificity as compared with other biomarkers, as creatin-chinase MB. However traditional troponin assays show some limits: the relatively long time elapsing between the onset of ischemia and the increase in serum concentration, and the difficulty in distinguishing ischemic from non ischemic damage. An earlier diagnosis could be obtained by adopting new high sensitivity troponin assays, with a coefficient of variation ≤10% at the 99° percentile of a reference healthy population, and capable of detecting circulating troponin in the most healty subjects. The difficulty in distinguishing ischemic from non ischemic harm can be overcome considering that only a rising and falling pattern can be attributed to ischemic harm. Further studies are needed to evaluate the prognostic role of low circulating troponin levels in healthy subjects and for properly fixing cut off values. Indeed biomarker increase has always to be considered in the specific clinical context.