Statins?is there no end to their usefulness?

Abstract

See also article by Birnbaum et al. [15] (pages 345–355) in this issue . Ever since the data from the West of Scotland Coronary Prevention (WOSCOP) Study demonstrated an unequivocal beneficial effect in patients at risk from coronary events [1], statins have become a standard addition to the therapeutic management of this group of the population. As inhibitors of HMG-CoA reductase, the primary pharmacodynamic effect of the statins is to inhibit the synthesis of cholesterol by the liver, thereby increasing hepatic cholesterol uptake and reducing circulating lipid levels–or is it? While lipid lowering is more than likely to underpin the clinical observations of a deceleration of atherosclerotic lesion formation and induction of regression and stabilisation of plaques, evidence is growing that the pleiotropic effects of statins (i.e. their effects beyond lipid lowering) may also contribute to their beneficial effects in this setting and may imply an earlier initiation of treatment. The pleiotropic effects of statins include an improvement in endothelial dysfunction and bioavailability of nitric oxide (NO), antioxidant potential, and anti-inflammatory properties. These properties immediately widen the scope for this increasingly versatile group of drugs. With respect to cardiovascular pathologies, statins have been shown to inhibit atrial myocardial remodelling [2,3], prevent atrial fibrillation [4], to conserve NO production in heart failure [5], to reduce the activity of small G-proteins in cardiac hypertrophy [6], and to contribute to post-ischaemic myocardial repair through mobilisation of endothelial progenitor cells [7]. A further potential use for statins is their ability to protect the myocardium from ischaemia/reperfusion injury. The infarct-limiting effects of statins have been observed with a number of different statins, including simvastatin, [8,9], pravastatin [10,11], and cerivastatin [12], in a range of experimental models. … *Tel.: +44 1224 262450; fax: +44 1224 262555. Email address: c.wainwright{at}rgu.ac.uk