Rosuvastatin (CRESTOR) - The Most Dangerous Cholesterol-Lowering Statin Drug

Rosuvastatin (CRESTOR) is the most dangerous of the popular cholesterol-lowering statin drugs, according to a new study. That was the finding of researchers from the Tufts-New England Medical Centerand Tufts University School of Medicine published in the May 23, 2005issue of the medical journal Circulation. Rosuvastatin is manufactured by AstraZeneca in Wilmington, Del.AstraZeneca sold more than $600 million worth of the drug in 2004 in the United Statesalone.

Public Citizen originally opposed the FDA approval of rosuvastatin, and we listed it as a DO NOT USE drug in September 2003 (see Worst Pills, Best Pills News October 2003). In March 2004, we petitioned the FDA to remove the drug from the market.

We are principally concerned about two types of adverse effects with rosuvastatin. The first is rhabdomyolysis, a life-threatening muscle adverse reaction that can lead to kidney failure and death. Rosuvastatin is the only statin in which rhabdomyolysis was seen in controlled clinical trials before the drug was approved. Even cerivastatin (BAYCOL), eventually banned because of rhabdomyolysis, did not have any cases of this occurring in the clinical trials before its approval.  

Second, rosuvastatin is unique among the statins in that early signs of kidney damage and blood and protein in the urine were also seen in pre-approval clinical trials. These are independent of the rhabdomyolysis risk. The kidney problems alone should have been sufficient for the FDA not to approve the drug, particularly because there is no evidence that rosuvastatin can lower the risk of either heart attack or stroke, which are the primary reasons for prescribing cholesterol-lowering drugs.

The Tufts researchers reviewed rosuvastatin-associated adverse reactions reported to the FDA over the drug’s first year on the market. They calculated the rates of adverse reactions per million prescriptions, using prescription data obtained from a market research firm specializing in prescription drugs. They compared the rates of rosuvastatin-associated adverse reactions over its first year of marketing with those seen with other statin drugs: atorvastatin (LIPITOR), simvastatin (ZOCOR), and pravastatin (PRAVACHOL).

They also compared rosuvastatin’s record with the first year of marketing of cerivastatin. Cerivastatin, you may remember, was banned from the market in August 2001 because of excessive deaths due to rhabdomyolysis (see Worst Pills, Best Pills News October 2001). The statins fluvastatin (LESCOL) and lovastatin (MEVACOR) were not included in the study.

The researchers compared the relative safety of the statin drugs by examining reports on several health problems associated with the statin drugs, including rhabdomyolysis, protein in the urine, kidney toxicity, or kidney failure. Rosuvastatin was found to be significantly more likely to be associated with rhabdomyolysis, protein in the urine, kidney toxicity, or kidney failure than the other statin drugs in the study.

Reported cases of rhabdomyolysis, protein in the urine, or kidney failure tended to occur early after the start of treatment and at relatively modest doses of rosuvastatin. The increased rate of rosuvastatin-associated adverse reactions relative to other widely used statins — atorvastatin, simvastatin, and pravastatin — was also observed when other categories of adverse reactions were examined. Those included adverse events with serious outcomes, liver toxicity, and muscle toxicity without rhabdomyolysis.

The researchers did find that now-banned cerivastatin had an even worse track record than rosuvastatin. During cerivastatin’s first year of marketing, the rate of reported cases of rhabdomyolysis, protein in the urine, or kidney failure was more than twice as great as it was for rosuvastatin. The rate of liver injury was about the same for the two drugs.

The researchers concluded that:

...rosuvastatin-associated adverse events reported to the US FDA raises concerns about the safety of this drug at the range of doses used in common clinical practice in the general population.

The type of research methodology used in this study was not the “gold standard” randomized, controlled clinical trial that can show a cause and effect relationship between taking a drug and the development of an adverse reaction. This was an epidemiological, or observational study of reports from the drug’s use in a wide population that technically cannot prove cause and effect. However, if done carefully and if certain criteria are fulfilled, causality can be presumed. Nevertheless, most of what we know about drug safety and what we are likely to know in the future will come from observational research.

Pharmaceutical companies criticize observational research when one of their drugs is found to have a safety problem, proclaiming that observational research proves nothing. They assert that proof of a problem is needed in the form of controlled clinical trials to conclusively show that one of their products is dangerous.  

This is monumentally disingenuous on the part of the industry, as they are aware that observational research is the standard for identifying drug safety problems. Moreover, it is unethical to conduct controlled clinical trials to measure a drug’s harm. They also know that the short-term controlled clinical trials used to gain a drug’s approval will not detect most serious safety problems. The pharmaceutical industry is not interested in sponsoring long-term drug safety research. The industry learned long ago that the less patients and physicians know about the safety of drugs, the easier they are to sell.

In this case, the Tufts research only adds to the previous body of evidence about the unacceptable level of harm that is potentially associated with use of rosuvastatin compared to other popular statin drugs. The original basis for concern about rosuvastatin comes from controlled clinical trials conducted before the drug was approved. Simply stated, rosuvastatin should have never been approved by the FDA.

What You Can Do

There is no medical reason why you should be taking rosuvastatin. If you are taking this drug to lower your cholesterol and need a statin drug, talk to your physician about switching to another statin that carries a smaller potential to cause harm, such as simvastatin, pravastatin, or atorvastatin.