Which is safer, atorvastatin or rosuvastatin?

In this article:

• Difference between atorvastatin and rosuvastatin
• Is atorvastatin safer than rosuvastatin?
• Atorvastatin side effects, interactions, and warnings
• Rosuvastatin side effects, interactions, and warnings
• Bottom line

In this article

• Difference between atorvastatin and rosuvastatin
• Is atorvastatin safer than rosuvastatin?
• Atorvastatin side effects, interactions, and warnings
• Rosuvastatin side effects, interactions, and warnings
• Bottom line

Statins are the most commonly recommended and prescribed cholesterol-lowering drugs, and within the drug class, atorvastatin and rosuvastatin are esteemed for their potency in reducing low-density lipoprotein cholesterol (LDL) levels, known as the “bad cholesterol.” As a result, they are frequently chosen for the prevention of heart attack and stroke in patients with the highest levels of risk. Choosing between the two medications could be a matter of your healthcare provider’s preference, but knowing about the potential side effects of atorvastatin and rosuvastatin can inform your decision. Certain adverse effects can be more likely with one, while other side effects occur more often with the other. 

Difference between atorvastatin and rosuvastatin

Atorvastatin and rosuvastatin are both generic medications that are also available as brand-name medications. Atorvastatin is available as brand-name Lipitor, and rosuvastatin is available as brand-name Crestor. Atorvastatin and rosuvastatin, like all statins, work by inhibiting the HMG CoA-reductase enzyme and thereby reducing lipid production in the liver. Because of their potency, the American Heart Association and American College of Cardiology classifies them as high-intensity statins. 

Both atorvastatin and rosuvastatin are available in tablet form with various dosing strengths, each taken once daily. Prices for the two drugs are similar. Without insurance, the average retail price of 30, 10 mg rosuvastatin tablets is $120, and the average retail price of rosuvastatin is $116 for 30, 10 mg tablets. With a SingleCare prescription discount card, you could pay $4 for atorvastatin and $6 for rosuvastatin. While quite similar, they do have their differences.

Metabolism

The liver metabolizes atorvastatin to a much higher extent than it metabolizes rosuvastatin. Specifically, the CYP3A4 enzyme is responsible for metabolizing atorvastatin. To a lesser extent, the CYP2C9 enzyme is responsible for metabolizing rosuvastatin.

Distribution

Rosuvastatin is more hydrophilic, meaning it tends to distribute into fatty tissues and cells. In contrast, rosuvastatin is carried by proteins in plasma and acts more specifically within the liver.

Potency

With regard to potency in lowering LDL cholesterol levels and triglycerides, rosuvastatin is more powerful than atorvastatin. As such, rosuvastatin may be better at reducing the risk of cardiovascular events than atorvastatin. They are equally recommended in national guidelines when high-intensity statin therapy is indicated, such as for the secondary prevention of another heart attack in the setting of coronary artery disease.

Is atorvastatin safer than rosuvastatin?

As you can see, there are important differences between the two titans of the statin world. Those distinctions may explain why rosuvastatin may carry a higher risk for some side effects, while atorvastatin has a higher risk for others. While neither can be labeled as safer overall, arguments can be made for either when it comes to specific adverse effects.

Muscle pain

Muscle pain (myalgia is a commonly feared statin side effect, along with extreme cases of rhabdomyolysis (muscle breakdown). One study found that rosuvastatin had similar rates of myalgia as placebo pills, while atorvastatin was more likely to cause muscle pain. This was just one study, though, and other studies indicate similar drug tolerability among both drugs. 

Kidney dysfunction

Kidney disease is a common concern among people with hypertension (high blood pressure) and diabetes mellitus, two conditions that often occur with high levels of LDL (bad) cholesterol. Some clinical trials have suggested that rosuvastatin may have the potential to cause abnormal kidney function tests, although other research refutes this. If there is a risk of this outcome, it is thought to be outweighed by the drug’s benefits in heart disease and atherosclerosis. Healthcare providers may choose to limit rosuvastatin dosage in people with severe kidney disease.

Diabetes mellitus

High lipid levels and high blood sugar (diabetes mellitus) frequently occur together. Although rosuvastatin was associated with higher rates of new-onset diabetes in some studies, it may still be advised for people with diabetes or who are at risk for diabetes. The reason is that these patients have a high risk of heart disease, which statins can lower. 

Memory loss

Case reports of memory loss associated with statin use, including atorvastatin, have raised alarms. The concerns revolved around whether atorvastatin and other lipophilic statins could cause adverse effects on brain function. On the other hand, dementia risk seems to be lowered by using statins. Once again, the benefits of atorvastatin are generally felt to outweigh any neurologic risk in most cases.

Drug interactions

Atorvastatin’s metabolism via the liver’s CYP3A4 enzyme puts it in conflict with more prescription drugs than rosuvastatin. Drug interactions can result in heightened or lessened effects of atorvastatin, and consequently, a patient could potentially experience more adverse effects from the statin or less cardiovascular benefit. Therapy with any statin runs a risk of drug interaction. If you’re a patient taking statins, it is important for you to report an accurate list of all medications and supplements you’re taking to your healthcare provider. 

Atorvastatin side effects, interactions, and warnings

Atorvastatin and its brand-name counterpart Lipitor are generally well-tolerated without side effects for most patients. The list of atorvastatin and Lipitor’s side effects seems less daunting when one realizes that the most common side effect described in the drug label, nasopharyngitis (cold symptoms), occurred in only about 8% of patients. Additional common side effects include:

• Joint pain and muscle pain or spasms
• Nausea and stomach upset
• Diarrhea
• Insomnia

Atorvastatin’s label calls attention to a few warnings that include muscle side effects, liver dysfunction, elevated blood sugar, and central nervous system problems.

As previously described, atorvastatin can interact with numerous other drugs—too many to be listed here. Some of the most noteworthy include the following:

• Fibrates like gemfibrozil
• Macrolide antibiotics like clarithromycin
• Antivirals like Paxlovid (nirmatrelvir-ritonavir)
• Antifungals like ketoconazole
• Digoxin
• Grapefruit juice

Rosuvastatin side effects, interactions, and warnings

Crestor is the brand-name version of rosuvastatin. Both rosuvastatin and Crestor’s side effects are similar to those of Lipitor (atorvastatin). The adverse effects are not that common and do not deviate a lot from the rates experienced by patients taking placebo, according to the drug’s label. The common side effects include the following:

• Joint and muscle pain
• Headache
• Abdominal pain
• Nausea or constipation
• Liver or muscle enzyme elevation on blood tests
• Diabetes mellitus

The highlighted warnings in rosuvastatin’s label call attention to the same concerns that atorvastatin’s label mentions. The risk of muscle, liver, blood sugar, or nervous system problems are all to be considered prior to starting the drug. Your healthcare provider will monitor your symptoms throughout rosuvastatin treatment.

Although rosuvastatin may not have as many drug interactions as atorvastatin, it is still an issue requiring caution. Healthcare providers will need to consider other prescription drugs, over-the-counter medications, and dietary supplements their patients take. Although this is not a complete list, examples include:

• Gout treatments like colchicine and febuxostat
• Fibrates like gemfibrozil
• Antivirals like Paxlovid (nirmatrelvir-ritonavir)
• The blood thinner Brilinta (ticagrelor)

Bottom line

The answer as to which is safer, atorvastatin or rosuvastatin, isn’t straightforward. Reports of muscle pains and memory loss with atorvastatin, along with more drug interactions, could point one toward taking rosuvastatin. But reports of disturbances in kidney function and blood sugar with rosuvastatin could make atorvastatin a better choice for some people. Ultimately, both drugs have impressive safety records and efficacy for preventing serious cardiovascular events. Talk to your healthcare provider about your specific concerns so you can make an informed choice that you’re both comfortable with.