Rosuvastatin (brand name Crestor, marketed by AstraZeneca) is one of the most commonly used statin drugs. Like other statins, rosuvastatin is prescribed to improve a person’s blood lipid levels and to reduce cardiovascular risk.
During the first decade or so that rosuvastatin was on the market, it was widely touted as a “third-generation statin,” and hence as being more effective and possibly causing fewer adverse effects than most other statin drugs. As the years have gone by and as evidence from clinical trials has accumulated, much of the early enthusiasm for this specific statin has become moderated.
Most experts now consider the relative risks and benefits of rosuvastatin to be largely similar to those of other statins. However, there are a few clinical circumstances in which rosuvastatin may be preferred.
Uses of Rosuvastatin
The statin drugs were developed to reduce blood cholesterol. These drugs bind competitively to the liver enzyme called hydroxymethylglutaryl (HMG) CoA reductase. HMG CoA reductase plays the rate-limiting role in the synthesis of cholesterol by the liver.
By blocking HMG CoA reductase, statins can significantly reduce LDL (“bad”) cholesterol production in the liver, and thus can reduce LDL cholesterol blood levels by as much as 60%. In addition, statins modestly lower blood triglyceride levels (by about 20-40%), and produce a small increase (about 5%) in blood levels of HDL cholesterol (“good cholesterol”).
With the exception of the recently developed PCSK9 inhibitors, statins are the most potent cholesterol-reducing drugs available. Furthermore, in contrast to the other classes of cholesterol-lowering drugs, clinical trials have shown that statin drugs can significantly improve the long-term outcomes of people with established coronary artery disease (CAD), and people at moderate or high risk of developing CAD.
Statins also significantly reduce the risk of subsequent heart attacks, and lower the risk of dying from CAD. (The newer PCSK9 inhibitors have also now been shown in large-scale RCTs to improve clinical outcomes.)
This ability of statins to significantly improve clinical outcomes is thought to result, at least in part, from some or all of their non-cholesterol-lowering benefits. In addition to lowering LDL cholesterol, statins also have anti-inflammatory properties, anti-blood clotting effects, and plaque-stabilizing properties. Furthermore, these drugs reduce C-reactive protein levels, improve overall vascular function, and reduce the risk of life-threatening cardiac arrhythmias.
It is very likely that the clinical benefits demonstrated by statin drugs are due to a combination of their cholesterol-lowering effects and their diverse array of non-cholesterol effects.
How Is Rosuvastatin Different?
Rosuvastatin is a newer, so-called “third-generation” statin drug. Essentially, it is the most potent statin drug on the market.
Its relative strength derives from its chemical characteristics, which allow it to bind more firmly to HMG CoA reductase, thus effecting a more complete inhibition of this enzyme. Molecule for molecule, rosuvastatin produces more LDL-cholesterol-lowering than other statin drugs. However, similar magnitudes of cholesterol-lowering can be achieved by using higher doses of most other statins.
When “intensive” statin therapy is needed to push cholesterol levels as low as possible, rosuvastatin is the go-to drug for many physicians.
Effectiveness of Rosuvastatin
Rosuvastatin has gained a reputation of being particularly effective among the statin drugs, mainly based on the results of two clinical trials.
In 2008, publication of the JUPITER study got the attention of cardiologists everywhere. In this study, over 17,000 healthy people who had normal blood LDL cholesterol levels but elevated CRP levels were randomized to receive either 20 mg per day of rosuvastatin or placebo.
During follow-up, people randomized to rosuvastatin not only had substantially reduced LDL cholesterol levels and CRP levels, but they also had significantly fewer cardiovascular events (including heart attack, stroke, the need for a revascularization procedure such as a stent or bypass surgery, and the combination of heart attack stroke, or cardiovascular death), as well as a reduction in all-cause mortality.
This study was remarkable not only because rosuvastatin significantly improved clinical outcomes in apparently healthy people, but also because these people did not have elevated cholesterol levels at the time of enrollment.
In 2016, the HOPE-3 trial was published. This study enrolled over 12,000 people with at least one risk factor for atherosclerotic vascular disease, but no overt CAD. Participants were randomized to receive either rosuvastatin or placebo. At the end of a year, people taking rosuvastatin had a significant reduction in a composite outcome endpoint (including nonfatal heart attack or stroke, or death from cardiovascular disease).
In both of these trials, randomization to rosuvastatin significantly improved the clinical outcomes of people who had one or more risk factors, but no signs of active cardiovascular disease.
It ought to be noted that rosuvastatin was chosen for these trials not because it was the most potent of the statin drugs, but (at least in large part) because the trials were sponsored by AstraZeneca, the maker of rosuvastatin.
Most lipid experts believe that the results of these trials would have been the same if another statin had been used at sufficient dosage, and in fact, current recommendations on therapy with statin drugs generally allow the use of any of the statin drugs as long as the dosage is high enough to achieve roughly the same level of cholesterol-lowering as would be achieved with a lower dose of rosuvastatin. (An exception to this general rule occurs when “intensive statin therapy” is called for. Intensive statin therapy is understood to mean either high-dose rosuvastatin or high-dose atorvastatin, which is the next-most-potent statin available.)
But because rosuvastatin was indeed the statin that was used in these two pivotal clinical trials, many doctors have defaulted to using rosuvastatin as their statin of choice.
Statin therapy is indicated to improve abnormal blood lipid levels (specifically, to reduce LDL cholesterol and/or triglyceride levels), and to prevent cardiovascular disease. Statins are recommended for people with established atherosclerotic cardiovascular disease, people with diabetes, and people whose estimated 10-year risk of developing cardiovascular disease is above 7.5% to 10%.
While, in general, the statin drugs are considered interchangeable in terms of their effectiveness and their risk of causing adverse events, there may be times when rosuvastatin might be preferred. Specifically, when “high-intensity” statin therapy is aimed at reducing LDL cholesterol to the lowest levels possible, either rosuvastatin or atorvastatin at their respective higher dose ranges are generally recommended.
Before you are prescribed any statin drug, your doctor will conduct a formal risk assessment to estimate your risk of developing cardiovascular disease and will measure your blood lipid levels. If you already have cardiovascular disease or are at substantially elevated risk of developing it, your doctor will likely recommend a statin drug.
Other commonly prescribed statin drugs include atorvastatin, simvastatin, fluvastatin, lovastatin, pitavastatin, and pravastatin.
Crestor, the brand name form of rosuvastatin in the U.S., is quite expensive, but generic forms of rosuvastatin are now available. If your doctor wants you to take rosuvastatin, ask if you can use a generic.
Statins should not be used in people who are allergic to statins or any of their ingredients, who are pregnant or breastfeeding, who have liver disease or renal failure, or who drink excessive amounts of alcohol. Studies show that rosuvastatin can be used safely in children over 10 years of age.
Dosage of Rosuvastatin
When rosuvastatin is being used to reduce elevated LDL cholesterol levels, usually lower doses are started (5 to 10 mg per day) and adjusted upwards every month or two as necessary. In people with familial hypercholesterolemia, doctors usually begin with somewhat higher doses (10 to 20 mg per day).
When rosuvastatin is being used to reduce the risk of cardiovascular disease in people with moderately elevated risk, the starting dose is usually 5 to 10 mg per day. In people whose risk is considered to be high (in particular, their 10-year risk is estimated to be above 7.5%), high-intensity therapy is often begun, with 20 to 40 mg per day.
If rosuvastatin is being used to reduce the risk of additional cardiovascular events in a person with already established cardiovascular disease, intensive treatment is usually employed with a dose of 20 to 40 mg per day.
In people taking cyclosporine or drugs for HIV/AIDS, or in people with reduced kidney function, the dose of rosuvastatin needs to be adjusted downwards, and generally should not exceed 10 mg per day.
People of Asian descent tend to be more sensitive to statin drugs and more prone to side effects. It is generally recommended that rosuvastatin should be started at 5 mg per day and increased gradually in Asian patients.
Rosuvastatin is taken once per day, and can be taken either in the morning or at night. Unlike several of the other statin drugs, drinking modest amounts of grapefruit juice has little effect on rosuvastatin.
Side Effects of Rosuvastatin
In the years immediately after rosuvastatin was developed, many experts postulated that statin side effects would be less pronounced with rosuvastatin, simply because lower doses could be used to achieve adequate cholesterol reduction. At the same time, other experts claimed that statin side effects would be magnified with this drug, since it was more potent than other statins.
In the intervening years, it has become apparent that neither assertion was correct. It looks like the type and magnitude of adverse effects is generally about the same with rosuvastatin as it is with other statin drugs.
Statins, as a group, are better tolerated than other cholesterol-reducing drugs. In a meta-analysis published in 2017 that looked at 22 randomized clinical trials, only 13.3% of people randomized to a statin drug discontinued the drug because of side effects within 4 years, compared to 13.9% of people randomized to placebo.
Still, there are well-recognized side effects caused by statin drugs, and these side effects generally apply to rosuvastatin as well as any other statin. The most notable of these side effects include:
Muscle-related adverse events. Muscle toxicity can be caused by statins. Symptoms may include myalgia (muscle pain), muscle weakness, muscle inflammation, or (in rare, severe cases) rhabdomyolysls. Rhabdomyolysis is acute renal failure caused by severe muscle breakdown. In most cases. muscle-related side effects can be controlled by switching to another statin. Rosuvastatin is among the statin drugs that appear to cause relatively little muscle toxicity. In contrast, lovastatin, simvastatin, and atorvastatin are more prone to cause muscle problems.
Liver problems. About 3% of people taking statins will have an increase in liver enzymes in their blood. In most of these people, no evidence of actual liver damage is seen, and the significance of this small elevation in enzymes is unclear. In a very few people, severe liver injury has been reported; it is not clear, however, that the incidence of severe liver injury is higher in people taking statins than in the general population. There is no indication that rosuvastatin produces more or fewer liver issues than other statins.
Cognitive impairment. The notion that statins can cause cognitive impairment, memory loss, depression, irritability, aggression, or other central nervous system effects has been raised, but has not been clearly demonstrated. In an analysis of case reports sent to the FDA, alleged cognitive problems associated with statins appear to be more common with lipophilic statin drugs, including atorvastatin, fluvastatin, lovastatin, and simvastatin. The hydrophilic statin drugs, including rosuvastatin, have been implicated less frequently with this potential adverse event.
Diabetes. In recent years, a small increase in the development of diabetes has been associated with statin therapy. A 2011 meta-analysis of five clinical trials suggests that one additional case of diabetes occurs in every 500 people treated with high-intensity statins. In general, this degree of risk is considered acceptable as long as the statin can be expected to substantially reduce overall cardiovascular risk.
Other side effects that have been commonly reported with statin drugs include nausea, diarrhea, and joint pain.
Taking certain drugs can increase the risk of developing side effects with rosuvastatin (or any statin). This list is a long one, but the most notable drugs that interact with rosuvastatin include:
Gemfibrozil , which is a non-statin cholesterol-lowering agent
Amiodarone, which is an anti-arrhythmic drug
Several of the HIV drugs
Some antibiotics, particularly clarithromycin and itraconazone
Cyclosporine, an immunosuppressant drug
A Word From Verywell
While rosuvastatin is the most potent statin available, in general, its effectiveness and toxicity profile is very similar to all the other statins. Still, there are a few clinical situations in which rosuvastatin may be preferred over other statin drugs.