Jenifer Smith, Pharm.D.
Clinical pharmacist specialist, Providence Health Plan
A new risk calculator has incited controversy over the potential for statin-based therapy to be used for primary prevention of atherosclerotic cardiovascular disease. The calculator is a companion tool to the new 2013 American College of Cardiology/American Heart Association guidelines for managing blood cholesterol, which take into account new factors, such as fatal and nonfatal stroke.
While it’s generally agreed that statin therapy reduces the risk of ASCVD events, there is concern the risk calculator could result in statin-based therapy for millions of new patients, mostly within the primary prevention cohort.1,2
The health care community worries that statins may have too many adverse effects to broadly prescribe for primary prevention, as the guidelines recommend. Some of these include muscle symptoms, incident diabetes mellitus, cognitive changes and elevated liver enzymes. However, not all of these are serious and the benefits of statins likely outweigh the risks in most patients.1
In practice, muscle symptoms (e.g., pain, soreness, weakness) related to statin therapy are commonly reported by patients and can increase with the dose. More severe side effects, such as myopathy and rhabdomyolysis, occur infrequently and are very rarely serious or life-threatening.
- If your patient develops severe muscle-related symptoms, consider discontinuing therapy and evaluating for possible myopathy or rhabdomyolysis.
- If symptoms are mild to moderate, discontinue therapy until the patient’s symptoms subside. Resume therapy with the original or a lower dose of the same statin.
- If your patient’s symptoms return, switch to another statin. You may want to consider a low-dose and titrating, depending on your patient’s tolerance level.
- If symptoms continue after two months, consider other causes and resume statin therapy at the original dose.
Statin use has been shown to increase the risk of developing Type 2 diabetes. However, in clinical trials and meta-analyses, the incidence of new-onset diabetes is relatively low. One meta-analysis of 13 randomized control trials evaluating over 90,000 patients showed that treating 255 patients for four years resulted in one additional case of diabetes. This same analysis showed that statin therapy prevented 5.4 vascular events (nonfatal MI or coronary heart disease death) in those same patients.2
The ACC/AHA guidelines recognize there is an increased risk of developing diabetes with statin-based therapy, but overall, the benefits of therapy are believed to outweigh the risks for most patients with a 10-year ASCVD risk at, or more than, 7.5 percent.
Take action: Patients on statin-based therapy should be monitored for diabetes according to current screening guidelines. The American Diabetes Association recommends:
- Asymptomatic patients receive a screening at least every three years, starting at age 45.
- If patients are overweight and have additional risk factors, such as physical inactivity or a first-degree relative with diabetes or hypertension, screenings may start earlier.4
- For patients with diabetes, statin therapy should be continued as the benefits associated with ASCVD risk reduction outweigh the risks associated with new-onset diabetes.1
In 2012, the Food and Drug Administration issued new safety labeling requirements for statin medications. At that time, postmarketing reports heightened concern that statin therapy could lead to cognitive impairment in some patients.5 Since then, the FDA has continued to monitor post marketing reports and has determined that symptoms, such as memory loss, forgetfulness and confusion generally are not serious and are reversible with discontinuation of the drug.6
A systematic review and meta-analysis looked at several clinical trials and did not find a true association between statin use and cognitive impairment. Richardson et al examined 27 studies and found that statin therapy did not increase the risk of dementia, Alzheimer’s disease or mild cognitive impairment (low- to moderate-quality evidence).
Subsequent meta-analysis of 10 cohort studies actually showed an association between statin therapy and decreased risk of dementia.7 Swiger et al also performed a systematic review of 11 randomized control trials and found that statins were not associated with short-term cognition deficits. Additionally, the authors found that statins may have a protective effect on cognition in long-term studies, as there was a 29 percent relative risk reduction in diagnosis of dementia.8
Take action: The ACC/AHA guidelines recommend that patients who develop symptoms of cognitive impairment while taking a statin should be evaluated for causes other than statin therapy, including exposure to other medications, neuropsychiatric and other systemic reasons.1
Some patients may experience increases in liver enzymes during routine use of statin therapy. However, the FDA has stated that these effects are transient and return to normal after statin therapy ceases. Recently, the FDA has concluded that liver injury is very rare with statin use and is not predicted by transient, elevated liver enzymes.5,6 Additionally, statins can be considered safe in patients with pre-existing mild hepatic impairment and nonalcoholic fatty liver disease.9
Take action: The FDA and the ACC/AHA guidelines recommend measuring baseline values for liver function prior to initiating statin therapy. Routine monitoring of liver function is not recommended unless your patient develops signs or symptoms of hepatotoxicity (unusual fatigue, abdominal pain, dark-colored urine, yellowing of the skin or sclera).1,6 In this case, interrupt therapy and determine the cause of symptoms. If statin therapy is not the cause of symptoms, consider restarting therapy.
To learn more, visit ProvLink and look for:
Pathways to Treat: ASCVD Risk Reduction
Do the Benefits of Statins Outweigh the Risks in Primary Prevention? (Providence Medical Group Clinical Pharmacy Department)
- 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.