What is the indication for Rosuvastatin (Crestor)?

From the Guidelines

Rosuvastatin is recommended as a high-intensity statin therapy for patients who require a significant reduction in LDL-C levels, with a typical starting dose of 20 mg once daily, which can be adjusted up to a maximum of 40 mg daily based on individual response and tolerance, as supported by the 2018 AHA/ACC/AACVPR/AAPA/ABC/ACPM/ADA/AGS/APhA/ASPC/NLA/PCNA guideline on the management of blood cholesterol 1.

Key Points

• Rosuvastatin is a potent statin medication that works by inhibiting HMG-CoA reductase, resulting in decreased LDL ("bad") cholesterol and triglycerides while slightly increasing HDL ("good") cholesterol.
• The medication is most effective when taken with lifestyle modifications, including a heart-healthy diet and regular exercise.
• Common side effects include muscle pain, weakness, and rarely, liver enzyme elevations.
• Patients should take rosuvastatin at the same time each day, with or without food, and report any unusual muscle pain or weakness to their healthcare provider immediately.
• Regular blood tests to monitor cholesterol levels and liver function are recommended, especially when starting therapy or adjusting dosage.
• Rosuvastatin may interact with certain medications, so patients should inform their doctor about all medications they're taking.

Dosage and Administration

• The typical starting dose of rosuvastatin is 20 mg once daily, which can be adjusted up to a maximum of 40 mg daily based on individual response and tolerance.
• According to the 2018 AHA/ACC/AACVPR/AAPA/ABC/ACPM/ADA/AGS/APhA/ASPC/NLA/PCNA guideline, rosuvastatin 20 mg (40 mg) is considered a high-intensity statin therapy, with an expected LDL-C lowering of ≥50% 1.

Clinical Evidence

• The CORONA trial (Controlled Rosuvastatin Multinational Trial in Heart Failure) and GISSI HF trial (Effects of n-3 PUFA and Rosuvastatin on Mortality-Morbidity of Patients With Symptomatic CHF) evaluated the efficacy and safety of initiation of 10 mg of rosuvastatin daily compared with placebo in patients with heart failure, and showed a significant reduction in the risk of total hospitalizations, hospitalizations for a cardiovascular cause, and hospitalizations for worsening HF 1.
• A subsequent patient-level analysis that pooled data from both these trials and accounted for competing causes of death showed a significant 19% reduction in the risk of MI with rosuvastatin in patients with ischemic HF, although the ARR was small 1.

From the FDA Drug Label

ROSUVASTATIN tablets, for oral use Initial U. S Approval: 2003 INDICATIONS AND USAGE Rosuvastatin tablets are an HMG Co-A reductase inhibitor (statin) indicated: To reduce the risk of major adverse cardiovascular (CV) events As an adjunct to diet to: reduce LDL-C in adults with primary hyperlipidemia. reduce LDL-C and slow the progression of atherosclerosis in adults reduce LDL-C in adults and pediatric patients aged 8 years and older with heterozygous familial hypercholesterolemia (HeFH). As an adjunct to other LDL-C-lowering therapies, or alone if such treatments are unavailable, to reduce LDL-C in adults and pediatric patients aged 7 years and older with homozygous familial hypercholesterolemia (HoFH) As an adjunct to diet for the treatment of adults with: Primary dysbetalipoproteinemia. Hypertriglyceridemia.

The main use of Rosuvastatin is to:

• Reduce the risk of major adverse cardiovascular events
• Lower LDL-C in various conditions, including primary hyperlipidemia, heterozygous familial hypercholesterolemia, and homozygous familial hypercholesterolemia
• Treat primary dysbetalipoproteinemia and hypertriglyceridemia in adults 2

From the Research

Rosuvastatin Overview

• Rosuvastatin is a potent statin used to reduce circulating low-density lipoprotein cholesterol (LDL-C) levels, enabling high-risk patients to achieve their lipid goals 3.
• It has a favorable balance of effects on atherogenic and protective lipoproteins, as well as pleiotropic effects, including anti-inflammatory and antioxidant effects, and improvement in endothelial dysfunction 3.

Efficacy and Safety

• Rosuvastatin has been shown to be effective in reducing LDL-C levels by 43% to 63% at doses of 10 to 40 mg/d, with a higher dose-to-dose potency compared to other statins 4.
• It is well tolerated, with rare incidences of myopathy and liver function test abnormalities, and has fewer clinically significant drug interactions due to its lack of metabolism by cytochrome P-450 enzymes 4, 5.
• Long-term treatment with rosuvastatin 40 mg has been shown to be safe and effective in patients with severe hypercholesterolemia, with 83% of patients achieving National Cholesterol Education Program (NCEP) Adult Treatment Panel (ATP) III LDL cholesterol goals at 12 weeks 6.

Clinical Benefits

• Rosuvastatin has been shown to reduce cardiovascular events in relatively low-risk subjects with elevated high-sensitivity C-reactive protein and normal LDL-C 3.
• It is an appropriate therapy in addition to antihypertensive treatment to reduce cardiovascular risk in hypertensive patients 3.
• Rosuvastatin-based lipid-lowering therapy can provide intensive LDL-C reductions, with a low risk of side effects, in patients at high vascular risk 7.

Patient Outcomes

• Rosuvastatin has been shown to enable significantly more patients to achieve their NCEP goals for LDL-C with lower doses, reducing the need for dose titration or combination therapy 4, 5.
• It has been effective in improving lipid profiles in patients with a broad spectrum of dyslipidemias, including those with hypercholesterolemia and high-risk patients 5.