What high-intensity statin (HMG-CoA reductase inhibitor) is associated with the least side effects?

From the Guidelines

Rosuvastatin at a dose of 20 mg is associated with the least side effects among high-intensity statins, as it provides a balance of high-intensity cholesterol-lowering effects with minimal side effects compared to other statins. When considering high-intensity statin therapy, it's essential to weigh the benefits of LDL-C lowering against potential side effects. According to the 2018 AHA/ACC/AACVPR/AAPA/ABC/ACPM/ADA/AGS/APhA/ASPC/NLA/PCNA guideline on the management of blood cholesterol 1, high-intensity statin therapy is defined as ≥50% LDL-C lowering. Some key points to consider when prescribing high-intensity statins include:

• The choice of statin and dose should be individualized based on the patient's risk factors, LDL-C levels, and potential for side effects.
• Rosuvastatin and atorvastatin are both high-intensity statin options, with rosuvastatin 20 mg and atorvastatin 80 mg being the specific doses evaluated in RCTs.
• Simvastatin 80 mg is not recommended due to the increased risk of myopathy, including rhabdomyolysis.
• Regular monitoring for side effects, such as liver enzyme elevations and muscle pain, is crucial when initiating high-intensity statin therapy.
• Taking the medication at night and maintaining adequate vitamin D levels may help minimize side effects. It's also important to note that individual responses to statin therapy can vary, and the percent reductions in LDL-C are estimates from data across large populations 1.

From the FDA Drug Label

The safety and effectiveness of rosuvastatin have not been established in pediatric patients younger than 8 years of age with HeFH, younger than 7 years of age with HoFH, or in pediatric patients with other types of hyperlipidemia (other than HeFH or HoFH). Advanced age (≥65 years) is a risk factor for rosuvastatin-associated myopathy and rhabdomyolysis Renal impairment is a risk factor for myopathy and rhabdomyolysis. Atorvastatin calcium tablets are contraindicated in patients with acute liver failure or decompensated cirrhosis Advanced age (≥65 years) is a risk factor for atorvastatin calcium tablets-associated myopathy and rhabdomyolysis Renal impairment is a risk factor for myopathy and rhabdomyolysis.

High-intensity statins are associated with a higher risk of side effects, including myopathy and rhabdomyolysis.

• Rosuvastatin and atorvastatin are both high-intensity statins, but the provided drug labels do not directly compare their side effect profiles.
• The labels do mention that advanced age and renal impairment are risk factors for myopathy and rhabdomyolysis for both drugs.
• However, the labels do not provide a direct comparison of the side effect profiles of rosuvastatin and atorvastatin, so no conclusion can be drawn about which one is associated with the least side effects 2 3.

From the Research

High-Intensity Statin Side Effects

• The study 4 found that atorvastatin is well tolerated and adverse events are usually mild and transient, with elevations of liver transaminases and creatine phosphokinase being infrequent.
• Another study 5 compared the safety of atorvastatin 80 mg and 40 mg in a veteran population and found that atorvastatin 80 mg was well tolerated with similar incidence of discontinuation and reduction of lipid panel values compared with atorvastatin 40 mg.
• However, a study 6 comparing high-intensity atorvastatin with rosuvastatin found that atorvastatin was associated with an increased incidence of adverse drug reactions, including abnormal liver transaminases and statin-associated muscle symptoms.

Comparison of High-Intensity Statins

• The study 6 found that rosuvastatin had a lower incidence of adverse drug reactions compared with atorvastatin, with patients receiving rosuvastatin being on therapy 2.5 times longer before developing an adverse drug reaction.
• The study 4 found that atorvastatin produced greater reductions in total cholesterol, LDL-cholesterol, and triglyceride levels compared with other HMG-CoA reductase inhibitors, including lovastatin, pravastatin, fluvastatin, and simvastatin.

Side Effect Profile of Atorvastatin

• The study 4 found that the tolerability profile of atorvastatin is similar to that of other available HMG-CoA reductase inhibitors and to placebo.
• The study 5 found that myalgia and weakness were commonly reported events among patients taking atorvastatin 80 mg and 40 mg, but the rates of discontinuation were similar between the two groups.
• The study 7 found that atorvastatin significantly lowered levels of triglyceride-rich remnant lipoproteins and favorably changed LDL particle size in patients with hypertriglyceridemia, which may explain the benefits of statin therapy in high-risk patients with hypertriglyceridemia.