[The best of 2001. Clinical pharmacology]

In the field of cardiovascular pharmacology the year 2001 has been marked by the demonstration of the clinical significance of new anti-thrombotics and by the interesting results with anti-endothelins. Whereas the failure of oral antiGPIIb-IIIa has been confirmed, melagatran (an anti-thrombin administered orally) and pentasaccharide (a new subcutaneous anti-Xa) have proved their efficacy in the prevention of venous thromboembolic disease compared to low molecular weight heparins, with an acceptable incidence of unwanted effects. Anti-endothelins under development have variable mechanisms of action from one drug to another. Their efficacy in cardiac insufficiency, pulmonary artery hypertension and arterial hypertension is suggested by clinical studies investigating small population; a more important study in decompensated cardiac insufficiency has not however shown a reduction of the morbidity and mortality with one of these drugs. The clinical significance of angiotensin II receptor antagonists has been confirmed for the indications which they share with ACE inhibitors (cardiac insufficiency, prevention of diabetic nephropathy). However, there are not enough comparative trials for these indications between these two classes in order to draw conclusions about the equivalence or superiority of one or the other. Of help elsewhere has been a re-interpretation of the mode of action of arterial wall drugs, and the inflammatory theory of atherosclerosis, putting the accent for example on the reduction of C reactive protein with a statin, or on the anti-inflammatory effect of aspirin. However, one study has not shown any benefit in giving a short course of corticosteroids in unstable angina. A very prominent event in the year 2001 remains the withdrawal of cerivstatin due to fatal rhabdomyolysis. The consequences go far beyond this drug, as its withdrawal justifies a fresh examination of the risk-benefit ratio for all the statins, with the probable corollary of a halt in the escalation of prescriptions. In this context, the new ezetimibe-type cholesterol absorption inhibitors could be a future solution.