Further Updates on the Cholesterol-Lowering Statin Drug Rosuvastatin (CRESTOR)

We have obtained new information about serious post-marketing adverse reactions — rhabdomyolysis and kidney failure — caused by the recently-approved cholesterol-lowering “statin” drug rosuvastatin (Crestor-AstraZeneca) and have also become aware of decisions by major U.S. health insurers and by the Swedish government not to reimburse for it. This information, coupled with a blistering attack on the drug by the Editor of the medical journal, The Lancet, re-emphasizes the basis for which we strongly urged the FDA not to approve it last year and subsequently urged readers not to use the drug once it was approved (see Worst Pills, Best Pills News, October 2003).

In opposing the drug’s approval, we pointed to the studies submitted by AstraZeneca to the FDA to gain approval for rosuvastatin. There were two cases of kidney failure and one case of kidney insufficiency in which patients had also experienced both protein and blood in the urine, an early sign of kidney toxicity. There were also a large number of patients who had blood and/or protein in their urine but had not suffered from kidney failure. In addition to this kidney toxicity, unique among all of the statin drugs, rosuvastatin is the only one of these drugs in which any cases of the life-threatening muscle destruction known as rhabdomyolysis was found to occur prior to approval. Even cerivastatin (BAYCOL), which was ultimately banned after at least 31 cases of fatal rhabdomyolysis, had not caused a single case of this adverse reaction prior to approval. In contrast, there were seven cases of rhabdomyolysis in patients receiving rosuvastatin before its approval. Although all were receiving a dose (80 milligrams) now no longer recommended, a small patient getting even the 40 milligram dose might be receiving the same amount of drug per pound of body weight. We were concerned that cases would occur at this dose or even lower doses.

The total number of new cases in Canada and the U.K. combined after the drug went on the market in those countries includes three patients with kidney failure, all of whom were taking the low dose of 10 milligrams; two additional patients with kidney damage, one taking the 10 milligram dose and the other, 20 milligrams; three patients with blood in their urine, two of whom were using either 10 or 20 milligrams; and three cases of rhabdomyolysis, two of whom were using either 20 milligrams or 40 milligrams.

Two major U.S. insurers, WellPoint, with 15 million patients insured, and Group Health Cooperative of Puget Sound (GHCPS) with more than 500,000 members have refused to reimburse for rosuvastatin. “We’ve already been Baycolled,” said Dr. Robert Seidman, chief pharmacy officer for the Thousand Oaks, California-based WellPoint, referring to Baycol, a statin that was taken off the market because of rhabdomyolysis. “There is a level of nervousness, and we’re being conservative and we’re being cautious,” Seidman added. Referring to concerns raised in the studies prior to its approval, he also said “I’m going to want to know what happens in real-life [use] of this product before I endorse it.”

Group Health Cooperative of Puget Sound stated, in its decision not to reimburse for the drug, that “Rosuvastatin offers no advantage over current formulary HMG-CoA reductase inhibitors [other statins] in terms of efficacy, safety, and cost. The effect of rosuvastatin on cardiovascular outcomes has not yet been studied and the safety of rosuvastatin beyond the one-year duration of clinical trials is unknown. Due to the recall of cerivastatin, the committee recommends using caution before prescribing statins with limited safety data.” In addition, a spokesperson from GHCPS expressed some concern about the known questions of safety based on evidence from the clinical trials. It is of particular interest that GHCPS has decided to reject rosuvastatin because in the past, they similarly rejected other drugs that came on the market with serious safety questions such as the pain-killer DURACT, the high blood pressure drug POSICOR, the diabetes drug REZULIN, and the weight reduction drug REDUX, all of which we listed as DO NOT USE drugs that were eventually banned by the FDA.

In Sweden, regional governmental drug advisors recommended against the use of the drug. The committees said in a statement that newer drugs such as rosuvastatin were not recommended because they did not meet the criteria of documented safety and cost effectiveness. The decision was unusual, because the representatives for Sweden’s regional governments were unanimous in their decision.

In an editorial in the October 25, 2003 issue of the British medical journal, The Lancet, the editor Dr. Richard Horton stated that:

“For AstraZeneca’s tactics in marketing its cholesterol-lowering drug, rosuvastatin, raise disturbing questions about how new drugs enter clinical practice and what measures exist to protect patients from inadequately investigated medicines. ...After a damaging delay over safety concerns, rosuvastatin finally won U.S. FDA approval in August and was launched last month, winning a 2% market share after only three weeks. [AstraZeneca CEO] McKillop has pledged to do whatever it takes to persuade doctors to prescribe rosuvastatin, including launching an estimated $1 billion first-year promotional campaign. ‘We’ve got to drive the momentum’, he said at a recent investors meeting. ‘You get one shot at launching a major new product. This is our shot.’

Why does the quality of debate about statins matter? First, because safety cannot be assured. Bayer withdrew cerivastatin in August, 2001, after the occurrence of unexpected cases of fatal rhabdomyolysis. The 80 mg dose of rosuvastatin was withdrawn by AstraZeneca because of safety concerns. Some critics are even anxious about the 40 mg dose. The finding of proteinuria [protein in the urine] and microscopic haematuria [blood in the urine] associated with rosuvastatin use are additional worries... Since there are no reliable data about efficacy [that is, actually decreasing heart attacks and strokes, not merely lowering cholesterol levels] and safety — and AstraZeneca is facing unusually acute commercial pressure to force rosuvastatin into the market — doctors should pause before prescribing this drug. Physicians must tell their patients the truth about rosuvastatin — that, compared with its competitors, rosuvastatin has an inferior evidence base supporting its safe use. AstraZeneca has pushed its marketing machine too hard and too fast. It is time for McKillop to desist from this unprincipled campaign.”

As we stated in our initial opposition to the approval of rosuvastatin, it is reasonably certain that this drug will, like, BAYCOL, have to be removed from the market. Unfortunately, this will be too late for the many people who will have suffered life-threatening muscle or kidney damage before it is banned.

What You Can Do

There is no medical reason for you to be taking rosuvastatin when there are three safer and more effective statins, in terms of reducing cardiovascular events, on the market.