Jenifer Smith, Pharm.D.
Clinical Pharmacist Specialist, Providence Health Plan
There is a wealth of evidence supporting the use of statins to reduce the risk of atherosclerotic cardiovascular disease (ASCVD).1-3 Based on this, the 2013 American College of Cardiology/American Heart Association cholesterol guidelines chose to recommend statin therapy for primary prevention patients aged 40 to 75 years with elevated LDL-cholesterol levels and a higher 10-year risk of developing ASCVD.4 Concern has been raised, however, that this may result in millions of new patients on statins with many more statin-related adverse effects.5 Fortunately, the risks related to statins are usually not severe, and for most patients, the benefits likely outweigh the risks.
Muscle symptoms (e.g., pain, soreness, and/or weakness) are commonly reported by patients taking statins. More severe side effects, such as myopathy and rhabdomyolysis, occur infrequently and are rarely serious or life-threatening.
- Severe symptoms: Discontinue therapy and evaluate for myopathy or rhabdomyolysis4
- Mild/moderate symptoms:4
- Consider discontinuing therapy until symptoms subside and resume therapy at original or lower dose. (If symptoms do not resolve, consider other causes and resume therapy)
- If symptoms return, switch to another statin. Start with a low-dose and titrate based on tolerance.
Although statin use has been associated with an increased risk of developing diabetes, the incidence is low. While a meta-analysis evaluating 90,000 patients showed that treating 255 patients for four years resulted in one additional case of diabetes, the same statin therapy prevented 5.4 vascular events (i.e., nonfatal MI or coronary heart disease death).6
- Screen for diabetes according to American Diabetes Association recommendations:7
- Asymptomatic patients: Screen every three years, starting at age 45.
- Start screening earlier in high-risk or symptomatic patients
- Patients with diabetes: Continue statin therapy and treat diabetes according to standards of care4
The Food and Drug Administration (FDA) has stated that cognitive symptoms (e.g., memory loss, forgetfulness, confusion) are generally not serious and are reversible with discontinuation of statin therapy.8,9 Systematic reviews, however, have failed to find an association between statin use and cognitive impairment, with some data suggesting a decreased risk of dementia.10,11
Take action: The ACC/AHA guidelines recommend continuing therapy and evaluating for other causes of cognitive impairment.4
Increased liver enzymes
Although liver enzyme elevation can occur during statin therapy, the FDA has concluded these effects are transient, normalize with discontinuation of statin therapy, and very rarely result in liver injury.8,9 Statins can also be safely prescribed for patients with pre-existing mild hepatic impairment and nonalcoholic fatty liver disease.12
- Measure baseline liver function prior to initiating statin therapy.
- Subsequent monitoring is only recommended if signs of hepatotoxicity are present.4,9
- Concern for hepatotoxicity: Interrupt therapy and determine the cause of symptoms. If statin therapy is not the culprit, restart therapy.
Given evidence supporting the use of statins to lower ASCVD risk in primary prevention, it is reasonable to start statins in patients with elevated cholesterol levels and a higher 10-year risk of developing ASCVD. Although there are side effects with statin therapy, they are rarely serious or life-threatening. If side effects do occur in your patients, they can be mitigated. As always, it is important to individualize therapy based on your patient’s history, background and beliefs. However, statin therapy is safe and effective for most patients.
ASCVD risk estimator app:
- Downs JR, Clearfield M, Weis S et al. Primary prevention of acute coronary events with lovastatin in men and women with average cholesterol levels: results of AFCAPS/TEXCAPS. Air Force/Texas Coronary Atherosclerosis Prevention Study. JAMA. 1998;279:1615-1622.
- Nakamura H, Arakawa K, Itakura H et al. Primary prevention of cardiovascular disease with pravastatin in Japan (MEGA Study): a prospective randomised controlled trial. Lancet. 2006;368:1155-1163.
- Ridker PM, Danielson E, Fonseca FA et al. Rosuvastatin to prevent vascular events in men and women with elevated C-reactive protein. N Engl J Med. 2008;359:2195-2207.
- Stone NJ, Robinson J, Lichtenstein AH et al. 2013 ACC/AHA Guideline on the Treatment of Blood Cholesterol to Reduce Atherosclerotic Cardiovascular Risk in Adults: A Report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. Circulation. 2013; 129:S1-S45.
- Pencina MJ, Navar-Boggan AM, D’Agostino RB et al. Application of New Cholesterol Guidelines to a Population-Based Sample. N Eng J Med. 2014;370:1422-1431.
- Sattar N, Preiss D, Murray HM et al. Statins and risk of incident diabetes: a collaborative meta-analysis of randomised statin trials. Lancet. 2010;375:735–42.
- American Diabetes Association. Standards of Medical Care in Diabetes – 2014. Diabetes Care. 2014; 37(S1):S14-S80.
- U.S. Food and Drug Administration. FDA Drug Safety Communication: Important safety label changes to cholesterol-lowering statin drugs. (Accessed 1 August 2014)
- U.S. Food and Drug Administration. For consumers: FDA Expands Advice on Statin Risks. (Accessed 1 August 2014)
- Richardson K, Schoen M, French B, et al. Statins and cognitive function: a systematic review. Ann Intern Med. 2013;159:688-697.
- Swiger KJ, Manalac RJ, Blumenthal RS, et al. Statins and cognition: a systematic review and meta-analysis of short- and long-term cognitive effects. Mayo Clin Proc. 2013;88:1213-1221.
- Gillett RC, Norrell A. Considerations for Safe Use of Statins: Liver Enzyme Abnormalities and Muscle Toxicity. Am Fam Physician. 2011 Mar 15;83(6):711-716.