AstraZeneca letter to The Lancet in response to publication of a letter by Public Citizen about Crestor

Main Category: Cholesterol
Article Date: 28 Jun 2004 - 9:00 PDT

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In response to the letter from Public Citizen (June 26, p 2189),1 rosuvastatin (Crestor) is a highly efficacious 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitor (statin) with a safety profile comparable to those of other marketed statins. AstraZeneca's ongoing review of post-marketed safety data as well as a recent review of data by health authorities worldwide, including the US Food and Drug Administration, supports this conclusion.

Because patients' safety is of paramount importance to AstraZeneca, rosuvastatin was the most extensively studied statin ever submitted for regulatory review. To date, regulatory authorities in more than 60 countries worldwide have approved rosuvastatin on the basis of the excellent benefit-risk profile, and over 2 million patients have now been treated with rosuvastatin.

Since rosuvastatin is the statin delivering the greatest reduction in LDL cholesterol (with the advantage of a significant increase in HDL cholesterol), more than 80% of patients can reach their LDL cholesterol goal on the usual start dose of rosuvastatin 10 mg. For the small number of patients with particularly severe hypercholesterolaemia who are inadequately treated with current monotherapies, titration to rosuvastatin 40 mg offers a therapeutic option.

Rhabdomyolysis is seen with all statins and is observed rarely across the full dose range. With continued marketed experience of rosuvastatin, the reporting rate of rhabdomyolysis has remained very rare by the Council for International Organizations of Medical Sciences' definition (<0.01%) and is consistent with the rates for all currently marketed statins.

Rare cases of fatal rhabdomyolysis have been reported with all other statins, but cerivastatin was unusual in that it was associated with 31 fatal reports of rhabdomyolysis on a background of nearly 10 million prescriptions.

For rosuvastatin, there have been no cases to date of fatal rhabdomyolysis, directly or indirectly related to the drug, on a background of over 5 million prescriptions.

Despite Public Citizen's claims to the contrary, rosuvastatin 10-40 mg is well tolerated from the renal perspective. In the clinical trial programme, proteinuria was seen in a small number of patients receiving rosuvastatin, comparator statins, and placebo.

This finding was thoroughly assessed for rosuvastatin and found to be transient, often resolved on continued treatment, and was not predictive of acute or progressive renal disease. Indeed, a recent publication reported that renal function in more than 10 000 patients treated with rosuvastatin for up to 3.8 years was maintained or tended to improve slightly.2

AstraZeneca is surprised that The Lancet has decided to publish a letter containing inappropriate data comparisons that only serve to cause undue alarm for patients whose dyslipidaemia is currently being successfully treated with rosuvastatin. In fact, this letter, which is a rehash of misinformation presented by Public Citizen in the past, includes reference to a non-marketed dose (80 mg) and is highly speculative.

In summary, rosuvastatin has an excellent benefit-risk profile compared with the other marketed statins, having better efficacy in lowering LDL cholesterol and raising HDL cholesterol and a safety profile comparable to those of the other marketed statins.

Gunnar O Olsson
gunnar.o.olsson@astrazeneca.com

AstraZeneca, Pepparedsleden 1, 431 83 Mölndal, Sweden

1 Wolfe SM. Dangers of rosuvastatin identified before and after FDA approval. Lancet 2004; 363: 2189-2190.

2 Vidt DG, Cressman MD, Harris S, Pears JS, Hutchinson HG. Rosuvastatin-induced arrest in progression of renal disease. Cardiology 2004; 102: 52-60.