The statin wars.

1 The Lancet. The statin wars: why AstraZeneca must retreat. Lancet 2003; 362: 1341. 2 Uretsky BG, Thygesen K, Armstrong PW, et al. Acute coronary findings at autopsy in heart failure patients with sudden death: results from the assessment of treatment with lisinopril and survival (ATLAS) trial. Circulation 2000; 102: 611–16. 3 Krum H, McMurray JJV. Statins and chronic heart failure: do we need a large-scale outcome trial? J Am Coll Cardiol 2002; 39: 1567–73. 4 Rauchhaus M, Coats AJ, Anker SD. The endotoxins-lipoprotein hypothesis. Lancet 2000; 356: 930–33. 5 Horwich TB, Hamilton MA, Maclellan WR, Fonarow GC. Low serum total cholesterol is associated with marked increased mortality in advanced heart failure. J Card Fail 2002; 8: 216–24. However, the success of such a strategy relies on a clear understanding of the side-effect profile of the molecule. An 80 mg dose of rosuvastatin clearly has an unacceptable side-effect profile. This issue was highlighted when the US regulatory authorities examined the New Drug Approval data, resulting in the Food and Drug Administration eventually granting a licence for rosuvastatin only at a dose range of 5–40 mg. Interestingly, the regulatory authorities of three European countries withdrew from the mutual recognition procedure to grant a licence for rosuvastatin. Finally, WellPoint Health Networks Inc—the USA’s second-largest private health insurer—has said it will not reimburse patients prescribed rosuvastatin because of concerns over the safety and benefits of the drug. I would suggest that, with increased experience of use by clinicians, the effective dose range of rosuvastatin could fall even further, thus providing a greater safety margin. It might well be, for example, that a dose of 2·5 mg might be clinically adequate for many patients. Indeed, as little as 1 mg of rosuvastatin provides over half the beneficial effect of an 80 mg dose. This would have major pricing and cost implications, and I can already hear the tablet splitters hard at work! The issue of pharmaceutical companies launching their products at a dose that turns out to be higher than is necessary is not a new one. Examples from the past include angiotensin-convertingenzyme inhibitors, blockers, thiazides, and oral contraceptives. Those who forget history are condemned to repeat it. Prescribers of rosuvastatin should consider the dose.