Atorvastatin, sold under the brand name Lipitor among others, is a statin medication used to prevent cardiovascular disease in those at high risk and to treat abnormal lipid levels. For the prevention of cardiovascular disease, statins are a first-line treatment in reducing cholesterol. It is taken by mouth.
Common side effects may include diarrhea, heartburn, nausea, muscle pain (typically mild and dose-dependent) and, less frequently, joint pain. Muscle symptoms often occur during the first year and are commonly influenced by pre-existing health issues and the nocebo effect. Most patients can continue therapy with dose adjustment or statin switching. Rare (<0.1%) but serious side effects may include rhabdomyolysis (severe muscle disorder), liver problems and diabetes. Use during pregnancy may harm the fetus. Like all statins, atorvastatin works by inhibiting HMG-CoA reductase, an enzyme found in the liver that plays a role in producing cholesterol.
Atorvastatin was patented in 1986, and approved for medical use in the United States in 1996. It is on the World Health Organization's List of Essential Medicines. It is available as a generic medication. In 2024, it was the most commonly prescribed medication in the United States, with more than 115million prescriptions filled for over 29 million people. In Australia, in 2023, it was the second most prescribed medication after Rosuvastatin.
Medical uses The primary uses of atorvastatin are for the treatment of dyslipidemia and for the prevention of cardiovascular disease.
Dyslipidemia Hypercholesterolemia (heterozygous familial and nonfamilial) and mixed dyslipidemia (Fredrickson types IIa and IIb) to reduce total cholesterol, LDL-C, apo-B, triglycerides levels, and CRP as well as increase HDL levels Heterozygous familial hypercholesterolemia in children Homozygous familial hypercholesterolemia Hypertriglyceridemia (Fredrickson Type IV) Primary dysbetalipoproteinemia (Fredrickson Type III) Combined hyperlipidemia
Cardiovascular disease Primary prevention of heart attack, stroke, and need for revascularization procedures in people who have risk factors such as age, smoking, high blood pressure, low HDL-C, and a family history of early heart disease, but have not yet developed evidence of coronary artery disease. Secondary prevention of all-cause mortality, myocardial infarction, stroke, major coronary events, ischaemic heart disease and revascularization in people with established coronary artery disease. The effect is dose-dependent and is amplified at higher doses. Close monitoring of liver function tests is required when high doses are used Alongside other lifestyle changes in primary and secondary prevention of angina Myocardial infarction and stroke prevention in people with type 2 diabetes
A 2014 meta-analysis showed high-dose statin therapy was significantly superior compared to moderate or low-intensity statin therapy in reducing plaque volume in people with acute coronary syndrome. The SATURN trial, which compared the effects of high-dose atorvastatin and rosuvastatin, also confirmed these findings.
Kidney disease Atorvastatin may have modest renal protective effects, such as reducing protein in the urine, but current evidence has not shown that it prevents progression to kidney failure.
Prior to contrast medium (CM) administration, pre-treatment with atorvastatin therapy can reduce the risk of contrast-induced acute kidney injury (CI-AKI) in people with pre-existing chronic kidney disease (CKD) (eGFR < 60mL/min/1.73m2) who undergo interventional procedures such as cardiac catheterisation, coronary angiography (CAG) or percutaneous coronary intervention (PCI).
A meta-analysis of 21 RCTs found that short-term high-dose statin therapy, including atorvastatin, was associated with a reduced incidence of contrast-induced acute kidney injury (CI-AKI) compared with low- or moderate-dose statin therapy or placebo in patients undergoing coronary angiography or percutaneous coronary intervention.
. Atorvastatin therapy can also help to prevent in-hospital dialysis post CM administration, however there is no evidence that it reduces all-cause mortality associated with CI-AKI. Overall, the evidence concludes that statin therapy, irrespective of the dose, is still more effective than no treatment or placebo at reducing the risk of CI-AKI.
Administration Statins (predominantly simvastatin) have been evaluated in clinical trials in combination with fibrates to manage dyslipidemia in people who also have type 2 diabetes, and a high cardiovascular disease risk; however, there is limited clinical benefit noted for most cardiovascular outcomes.
While statins with short half-lives (with half-lives of 2-4 hours, such as simvastatin, pravastatin, lovastatin) has a greater LDL-C and TC (and potentially TG) reduction effects when being taken in the evening time, so that their peak blood concentrations cover the peak of natural cholesterol synthesis in the body, the administration time difference of statins with long half-lives (such as atorvastatin, rosuvastatin) on therapeutic efficacies of cholesterol-lowering (including LDL-C, HDL-C, TC and TG) could not be established. A recent meta-analysis suggested that statins with longer half-lives, including atorvastatin, may also be more effective at lowering LDL cholesterol if taken in the evening. However, the only study included in the meta-analysis of atorvastatin in people with heart disease did not specifically investigate if morning or evening dosing was more effective for reducing LDL cholesterol. The trial did confirm that, irrespective of dosing time, atorvastatin is very effective at reducing total cholesterol, LDL cholesterol, and triglycerides, and increasing HDL cholesterol levels. Hence, atorvastatin should be taken at the same time each day, at a time that is most convenient for the patient, so it does not compromise compliance.
Specific populations Geriatric: Plasma concentrations of atorvastatin in healthy elderly subjects are higher than those in young adults. Clinical data suggests a comparable reduction in cardiovascular events among geriatric population and adults under 65 years of age. However, limited information is available on the benefits of use in patients over 75 years old who have not already had a cardiovascular event such as a heart attack. Pediatric: Pharmacokinetic data is not available for this population. Gender: Plasma concentrations are generally higher in women than in men, but there is no clinically significant difference in the extent of LDL reduction between men and women. Kidney impairment: Kidney disease has no statistically significant influence on plasma concentrations of atorvastatin and dose adjustment considerations should only be made in context of the patient's overall health. Hemodialysis: Previous studies have demonstrated a lack of clear and significant clinical benefit of statins (including atorvastatin 20 mg) in reducing composite cardiovascular and all-cause mortality in adults on hemodialysis (including those with pre-existing cardiovascular disease(s) and/or diabetes), despite a reduction in total/ LDL cholesterol levels. The SHARP study suggested that the combination of a statin and ezetimibe is effective in reducing the risk of major atherosclerotic events in all CKD populations, including those on dialysis, but could not establish mortality benefit. Although limited studies have identified that statins may reduce all-cause mortality and composite cardiac events in hemodialysis patients with a higher baseline LDL-C level (>3.75 mmol/L), findings are inconsistent and potentially misleading. Evidence suggests that LDL-C levels are not a reliable predictor of mortality in the hemodialysis population given the complex interplay of patient factors in ESRD. Therefore, LDL-C levels cannot be considered a true predictor of composite risk. Additionally, the impact and relevance of hemodialysis on statin levels and efficacy were not addressed in these trials. Liver impairment: Increased drug levels can be seen in people with advanced cirrhosis. Despite these concerns, a 2017 systematic review and analysis of available evidence has shown that statins, such as atorvastatin, are relatively safe to use in stable, asymptomatic cirrhosis and may even reduce the risk of liver disease progression and death.
Contraindications Active liver disease: cholestasis, hepatic encephalopathy, hepatitis, and jaundice Pregnancy: Atorvastatin was previously classified as a pregnancy Category X medication by the U.S. Food and Drug Administration, indicating that it was contraindicated during pregnancy. In July 2021, this classification was removed and replaced with updated labelling advising discontinuation of statins during pregnancy and consultation with a healthcare professional. Recent systematic reviews and meta-analyses found no increased risk of major congenital anomalies associated with statin exposure. While some observational studies reported associations with stillbirth, spontaneous abortion and low birth weight, findings remain inconsistent and may reflect maternal comorbidities rather than a direct causal effect of statins. Statins, including atorvastatin, act by inhibiting HMG-CoA reductase, an enzyme that catalyzes the biosynthesis of cholesterol. Cholesterol is essential for fetal development, particularly during early embryogenesis, as it plays a critical role in cell membrane formation and steroid hormone production. Due to these concerns, atorvastatin should be discontinued prior to conception or as soon as pregnancy is confirmed. Breastfeeding: Small amounts of other statin medications have been found to pass into breast milk, although atorvastatin has not been studied specifically. Due to risk of disrupting a breastfeeding infant's metabolism of lipids, atorvastatin is not regarded as compatible with breastfeeding. Markedly elevated CPK levels or if a myopathy is suspected or diagnosed after dosing of atorvastatin has begun. Very rarely, atorvastatin may cause rhabdomyolysis, and it may be very serious leading to acute kidney injury due to myoglobinuria. When rhabdomyolysis is suspected or diagnosed, atorvastatin therapy is discontinued immediately. The likelihood of developing a myopathy is increased by the co-administration of cyclosporine, fibric acid derivatives, erythromycin, niacin, and azole antifungals.
Side effects
Major Type 2 diabetes is observed in a small number of people, and is an uncommon class effect of all statins. It appears it may be more likely in people who were already at a higher risk of developing diabetes before starting a statin due to multiple risk factors, for example raised fasting glucose levels. However, the benefits of statin therapy in preventing fatal and non-fatal stroke, fatal coronary heart disease, and non-fatal myocardial infarction are significant. For most people the benefits of statin therapy far outweigh the risk of developing diabetes. A 2010 meta-analysis demonstrated that every 255 people treated with a statin for four years produced a reduction of 5.4 major coronary events and induced only one new case of diabetes. In some case and clinical studies mild muscle pain or weakness have been reported (around 3%), compared to a placebo. However, this increase was not related to statin therapy in 90% of cases in a large meta-analysis of randomized controlled trials. In patients taking higher statin doses, a similarly low increase in muscle pain and weakness was present (5%) with no clear evidence of a dose-response relationship. Duration of treatment with atorvastatin is unlikely to increase the risk of muscle-related side effects as most occur within the first year of treatment, after which the risk is not increased further. The known cardiovascular benefits of atorvastatin over time outweigh the low risk of muscle-related side effects.