Rosuvastatin

The effects of rosuvastatin on low-density lipoprotein (LDL) cholesterol are dose-related. Higher doses were more efficacious in improving the lipid profile of patients with hypercholesterolemia than milligram-equivalent doses of atorvastatin and milligram-equivalent or higher doses of simvastatin and pravastatin.[11]

Meta-analysis showed that rosuvastatin is able to modestly increase levels of high-density lipoprotein (HDL) cholesterol as well, as with other statins.[12] A 2014 Cochrane review determined there was good evidence for rosuvastatin lowering non-HDL levels linearly with dose.[13]

As with all statins, there is a concern of rhabdomyolysis, a severe undesired side effect. The U.S. Food and Drug Administration (FDA) has indicated that "it does not appear that the risk [of rhabdomyolysis] is greater with Crestor than with other marketed statins", but has mandated that a warning about this side-effect, as well as a kidney toxicity warning, be added to the product label.[20][21]

Statins increase the risk of diabetes,[22] consistent with FDA's review, which reported a 27% increase in investigator-reported diabetes mellitus in rosuvastatin-treated people.[23]

Because low- to moderate dose statins are strongly recommended by the United States Preventive Services Task Force (USPSTF) for primary prevention of cardiovascular disease in adults aged 40–75 years who are at risk,[31] the Patient Protection and Affordable Care Act (PPACA) in the United States requires most health insurance plans to cover the costs of these drugs without charging the insured patient a copayment or coinsurance, even if he or she has not yet reached his or her annual deductible.[32][33][34] Rosuvastatin 5 mg and 10 mg are examples of regimens meeting the USPTFS guideline;[31] however, insurers have discretion as to which low- and moderate-dose statin regimens to cover under this requirement,[35] and some only cover other statins.[36]

The drug was billed as a "super-statin" during its clinical development; the claim was that it offers high potency and improved cholesterol reduction compared to rivals in the class. The main competitors to rosuvastatin are atorvastatin and simvastatin. However, people can also combine ezetimibe with either simvastatin or atorvastatin and other agents on their own, for somewhat similar augmented response rates. As of 2006 some published information for comparing rosuvastatin, atorvastatin, and ezetimibe/simvastatin results is available, but many of the relevant studies are still in progress.[25]

First launched in 2003, sales of rosuvastatin were $129 million and $908 million in 2003, and 2004, respectively, with a total patient treatment population of over 4 million by the end of 2004. Annual cost to the UK National Health Service (NHS) in 2018, for 5–40 mg rosuvastatin daily was £24-40, compared to £10-20 for 20–80 mg simvastatin.[37]

In 2013, it was the fourth-highest selling drug in the United States, accounting for approximately $5.2 billion in sales.[38] In 2020, it was the seventeenth most commonly prescribed medication in the United States, with more than 29 million prescriptions.[9]

Rosuvastatin is approved in the United States for the treatment of high LDL cholesterol (dyslipidemia), total cholesterol (hypercholesterolemia), and/or triglycerides (hypertriglyceridemia).[39] In February 2010, rosuvastatin was approved by the FDA for the primary prevention of cardiovascular events.[40]

As of 2004, rosuvastatin had been approved in 154 countries and launched in 56. Approval in the United States by the Food and Drug Administration (FDA) came on 13 August 2003.[41][42]

The main patent protecting rosuvastatin (RE37,314 — due to expire in 2016) was challenged as being an improper reissue of an earlier patent. This challenge was rejected in 2010, confirming protection until 2016.[43][44][45][46][47]

In April 2016, the FDA approved the first generic version of rosuvastatin (from Watson Pharmaceuticals Inc).[48] In July 2016, Mylan gained approval for its generic rosuvastatin calcium.[49]

In October 2003, several months after its introduction in Europe, Richard Horton, the editor of the medical journal The Lancet, criticized the way Crestor had been introduced. "AstraZeneca's tactics in marketing its cholesterol-lowering drug, rosuvastatin, raise disturbing questions about how drugs enter clinical practice and what measures exist to protect patients from inadequately investigated medicines," according to his editorial. The Lancet's editorial position is that the data for Crestor's superiority rely too much on extrapolation from the lipid profile data (surrogate end-points) and too little on hard clinical end-points, which are available for other statins that had been on the market longer. The manufacturer responded by stating that few drugs had been tested so successfully on so many patients. In correspondence published in The Lancet, AstraZeneca's CEO Tom McKillop called the editorial "flawed and incorrect" and slammed the journal for making "such an outrageous critique of a serious, well-studied medicine."[50]

In 2004, the consumer interest organization Public Citizen filed a Citizen's Petition with the FDA, asking that Crestor be withdrawn from the US market. On 11 March 2005, the FDA issued a letter to Sidney M. Wolfe of Public Citizen both denying the petition and providing an extensive detailed analysis of findings that demonstrated no basis for concerns about rosuvastatin compared with the other statins approved for marketing in the United States.[51] In 2015, Wolfe explained why he thought that "the drug should have been withdrawn and why it should not be used", due to the incidence of rhabdomyolysis, renal problems, and significant increase in glycated hemoglobin (HbA_1C) and fasting insulin levels, and decreased insulin sensitivity in diabetic patients. Rosuvastatin indeed lowered cholesterol more than other statins, but Wolfe asked "what about actually improving health, preventing heart attacks and strokes?"[10]