Currently, there are seven U.S. FDA-approved statins on the market and available for use: atorvastatin, fluvastatin, lovastatin, pitavastatin, pravastatin, rosuvastatin and simvastatin. While the medical community is certain statins significantly reduce the risk of vascular events and cardiovascular mortality in high-risk patients, the choice of which statin to use in a specific patient is not always as clear. Not all statins are created equal and differences in their lipophilicity, potency and pharmacokinetic parameters can impact patient response.
UCHealth Integrated Network is actively and diligently working to improve the use of statins in patients with diabetes using collaborative approaches that include providers, clinical pharmacists and other health care team members. The current initiatives to date (e.g., Epic Health Maintenance tool, pharmacist chart review with recommendations to providers) have been effective in identifying patients who may benefit from statin therapy. The choice of statin for a specific patient is, ultimately, at the discretion of the prescribing physician.
To optimize the use of statin therapy, clinicians should consider several factors when selecting a specific statin drug for a patient. The goal is to maximize drug efficacy and patient tolerability to ensure patients remain adherent to their statin therapy.
Factors to consider when choosing a statin:
- Indicated statin intensity based on evidence.
- History of statin use and intolerance.
- Patient adherence.
- Drug-drug interactions.
- Renal function.
Indicated statin intensity.
It important to first identify patients who are indicated for statin therapy as well as the level of statin-intensity that should be utilized in those patients. The 2018 ACC/AHA Guideline on the Treatment of Blood Cholesterol to Reduce Atherosclerotic Cardiovascular Risk in Adults1 outlines four statin benefit groups and provides recommendations on statin-intensity based on a large body of clinical trials.
LDL-C: low-density lipoprotein cholesterol.
High-intensity statins lower LDL-C by at least 50 percent on average while moderate-intensity statins lower LDL-C by approximately 30-49% on average. The table below outlines the specific statins and doses for low-, moderate-, and high-intensity statin therapy.
The available statins differ in how water-soluble (hydrophilic) versus fat-soluble (lipophilic) they are. Statins that are lipophilic tend to distribute more into the body’s tissues as compared to hydrophilic statins. In patients who have a history of statin intolerance due to muscle-related adverse effects (e.g., myalgia), choosing a statin that is hydrophilic may be better tolerated due to less distribution into the body’s tissues.
Statins also differ in their half-lives affecting their overall duration of action. Some statins are considered to have short half-lives and should be dosed in the evening when LDL-C production is highest in order to maximize their effect. In contrast, statins with long half-lives can be dosed at any time of the day due to their longer duration of action and may be more optimal in patients who have issues with adherence.
Lastly, the potential for drug-drug interactions should be considered when selecting the most appropriate statin for a patient. Drug-drug interactions with statins can increase risk of adverse effects with statin therapy which may deter patients from maintaining statin therapy. Several statins are metabolized through the cytochrome P450 (CYP) pathway. Simvastatin and lovastatin (and to a lesser extent atorvastatin) are metabolized by CYP3A4 and are therefore most likely to have drug-drug interactions. Pravastatin is not metabolized through the CYP pathway and is a good option for patients who may be on multiple other drugs that affect CYP enzymes. In general, gemfibrozil should be avoided with all statins. The table below provides a list of select interactions that are commonly seen in clinical practice.
Note: this is not an all-inclusive list of statin interactions.
According to the 2018 ACC/AHA Guidelines, it is not recommended to initiate statin therapy in patients with advanced kidney disease who require dialysis treatment. In patients with chronic kidney disease not on hemodialysis, it is useful to consider urinary excretion of statin medications when choosing statin therapy. Atorvastatin and fluvastatin have the least urinary excretion, and may be the best choice in individuals with impaired renal function. Although only 10 percent of rosuvastatin is eliminated in the urine, it should be used cautiously in patients with decreased renal function because its long half-life can increase serum concentrations.
Given the magnitude of benefit that statins provide to our patients in terms of cardiovascular morbidity and mortality, it is essential we select a statin that is both evidence-based and will be best tolerated by the patient to ensure continued use.
≠Metabolized through CYP2C9, so would need to avoid in some situations.
Questions or comments? Please contact Joseph.VandeGriend@uchealth.org.
Marina L. Maes, PharmD and Marina S. Snellings, PharmD authored this article. They are both second-year ambulatory care pharmacy residents with the University of Colorado Skaggs School of Pharmacy and provide clinical pharmacy services to patients across the UCHealth Clinically Integrated Network.
- Grundy SM, Stone NJ, Bailey AL, et al. 2018 AHA/ACC/AACVPR/AAPA/ACPM/ADA/AGS/APhA/ASPC/NLA/PCNA guideline on the management of blood cholesterol: a report of the American College of Cardiology/American Heart Association Task Force on clinical practice guidelines. J Am. Coll Cardiol, Nov 2018, 25709; doi: 10.1016/j.jacc.2018.11.003.
- Venero CV, Thompson PD. Managing statin myopathy. Endocrinol Metab Clin North Am. 2009 Mar;38(1):121-36. doi: 10.1016/j.ecl.2008.11.002.