Healthy Skepticism International News
June 2002
Cerivastatin and fatal rhabdomyolysis: not just a safety issue.
June 2002 Vol 20 No 6
By Juan Gérvas and Mercedes Pérez-Fernández
Bayer has voluntarily withdrawn cerivastatin from the world market after almost one hundred reported deaths[1] and an unknown number of unreported deaths associated with rhabdomyolysis. It is hard to believe that the European Medicines Evaluation Agency is only now undertaking the first comprehensive safety evaluation of statins since their debut into clinical use prompted by that withdrawal.[2] However, the cerivastatin affair triggers more questions than just regarding the safety of statins [1].
Cerivastatin was approved on the basis of surrogate efficacy. Should we continue to approve drugs on that basis? The use of surrogate end points for reaching conclusions about drug benefits has caused rising concern and the cerivastatin affair confirms that such concern is well justified.[3,4] Disappointingly neither the U.S.A. nor the E.U. authorities have discussed or reviewed this question in response to the cerivastatin withdrawal.
The risk of fatal rhabdomyolysis was found to be higher among patients who received the full dose (0.8 mg/day in the USA and 0.4 mg/day in the EU) and those who received gemfibrozil concomitantly. It is important to ask two additional questions that appear to have the same answer: 1) Why did doctors use cerivastatin this way? 2) How was cerivastatin marketed? Cerivastatin was promoted as “a first line agent for hypercholesterolaemia”, “safe and effective for patients who require aggressive LDL cholesterol lowering to achieve NCEP-recommended targets” [5]. We are hoping for some explanation, some re-analysis of the original data from The Cerivastatin Group (USA) [6], The Canadian Cerivastatin Study Group [7] and The International Cerivastatin Study Group (Belgium, France, Germany, Israel, Italy, Netherlands, Norway, South Africa, Spain, Sweden and the United Kingdom) [8] at least.
The cerivastatin fatal rhabdomyolysis affair should be use as an example to stimulate reconsideration of the whole process of drug approval, marketing and use, as occurred after thalidomide was found to cause adverse effects to the foetus. It is not just a safety issue [1].
-Juan Gérvas, MD, PhD, Equipo CESCA, Madrid. General practitioner, Canencia de la Sierra (Madrid). Spain
Mercedes Pérez-Fernández, MD, Equipo CESCA, Madrid, Spain.
-Postal address: TravesÃa de la Playa, 3. Buitrago del Lozoya (Madrid), Spain.
-Fax: +34 91 8681451
-e-mail: .(JavaScript must be enabled to view this email address)
1.- Staffa JA, Chang J, Green L. Cerivastatin and reports of fatal rhabdomyolysis. N Engl J Med 2002;346:539-540 [letter]
2.- Farmer JA. Learning from the cerivastatin experience. Lancet 2001;358:1383-1385 [letter]
3.- Temple R. Are surrogate markers adequate to assess cardiovascular disease drugs?. JAMA 1999;282:790-795.
4.- Furgerg CD, Pitt B. Withdrawal of cerivastatin from the world market. Curr Control Trials Cardiovascular Med 2001;2;205-207
5.- Plosker GL, Dunn CI, Figgitt DP. Cerivastatin: a review of its pharmacological properties and therapeutic efficacy in the management of hypercholesterolaemia. Drugs 2000;60:1179-1206
6.- Dujovne CA, Knopp R, Kwiterovich P, Hunninghake D, McBride TA, Poland M. Randomized comparison of the efficacy and safety of cerivastatin and pravastatin in 1030 hypercholesterolemic patients. Mayo Clin Proc 2000;75:1124-1132
7.- McPherson R, Hanna K, Agro A, Braeken A. Cerivastatin versus branded pravastatin in the treatment of primary hypercholesterolaemia in primary care practice in Canada: a one-year, open-label, randomized, comparative study of efficacy, safety, and cost-effectiveness. Clin Ther 2001;23:1492-1507
8.- Betteridge DJ. International multicentre comparison of cerivastatin with placebo and simvastatin for the treatment of patients with primary hypercholesterolaemia. Int J Clin Pract 1999;53:243-250
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