Research and Literature

Professional Refresher: AHA/ACC Guidelines on the Treatment of Blood Cholesterol to Reduce Atherosclerotic Cardiovascular Risk in Adults: Safety Recommendations (Statin and Nonstatin)

January 11, 2017   /

What are these guidelines?
The American Heart Association (AHA) and the American College of Cardiology (ACC) began work in 2008 to compile and transform evidenced-based research and outcomes into doable guidelines to better the heart health of the American people. 

How were the guidelines created?
Work groups, consisting of health professionals and researchers in the field, were formed. Each group looked at a different component of heart health and compiled the best and most relevant research studies and results. These work groups then established guidelines based on the available evidence. 
 

How can they help my patients?
These guidelines are intended to guide physicians and health professionals to better reduce the risk for cardiovascular events, like heart attacks and high blood pressure, in their patients. 
However, these specific guidelines may be more confusing compared to other guidelines due to the extensive use of medical language and abbreviations. 

What are the specific guidelines?
The Guidelines on the Treatment of Blood Cholesterol to Reduce Atherosclerotic Cardiovascular Risk in Adults were divided into 3 components: 1) Statin treatment recommendations, 2) Safety recommendations, and 3) Recommendations for Monitoring, Optimizing, and Addressing Insufficient Response to Statin Therapy. Due to the length of these specific guidelines, each component has been separated into its own document. The remaining 4 components, as well as other sets of guidelines from the report, can be found at www.nutrtion411.com in the Heart Health Information Center.

The guidelines below are copied directly from the report, which can be assessed at http://circ.ahajournals.org/content/129/25_suppl_2/S1.full

Component 2: Safety Recommendations (Statin and Nonstatin)

  1. Statin safety recommendations
    1. To maximize the safety of statins, selection of appropriate statin and dose in men and nonpregnant/nonnursing women should be based on patient characteristics, level of atherosclerotic cardiovascular disease (ASCVD) risk, and potential for adverse side effects. Moderate-intensity statin therapy should be used in individuals in whom high-intensity statin therapy would otherwise be recommended when characteristics predisposing them to statin-associated adverse effects are present. 
      1. Characteristics predisposing individuals to statin adverse effects include but are not limited to:
        1. Multiple or serious comorbidities, including impaired renal or hepatic function
        2. History of previous statin intolerance or muscle disorders
        3. Unexplained alanine transaminase (ALT) elevations ≥ 3 times the upper limit of normal (ULN)
        4. Patient characteristics or concomitant use of drugs affecting statin metabolism
        5. Age > 75 years
      2. Additional characteristics that could modify the decision to use higher statin intensities might include but are not limited to:
        1. History of hemorrhagic stroke
        2. Asian ancestry
    2. Creatine kinase (CK) measurements
      1. CK should not be routinely measured in individuals receiving statin therapy.
      2. Baseline measurement of CK is reasonable for individuals believed to be at increased risk for adverse muscle events because of a personal or family history of statin intolerance or muscle disease, clinical presentation, or concomitant drug therapy that might increase the risk of myopathy.
      3. During statin therapy, it is reasonable to measure CK in individuals with muscle symptoms, including pain, tenderness, stiffness, cramping, weakness, or generalized fatigue. 
    3. Hepatic transaminase measurements
      1. Baseline measurement of hepatic transaminase levels (ALT) should be performed before initiation of statin therapy.
      2. During statin therapy, it is reasonable to measure hepatic function if symptoms suggesting hepatotoxicity arise (eg, unusual fatigue or weakness, loss of appetite, abdominal pain, dark-colored urine, or yellowing of the skin or sclera).
    4. Decreasing the stain dose may be considered when 2 consecutive values of low density lipoprotein-cholesterol (LDL-C) levels are < 40 milligrams (mg)/deciliter (dL).
    5. It may be harmful to initiate simvastatin at 80 mg daily or increase the dose of simvastatin to 80 mg daily. 
    6. Individuals receiving statin therapy should be evaluated for new-onset diabetes according to the current diabetes screening guidelines. Those who develop diabetes during statin therapy should be encouraged to adhere to a heart-healthy dietary pattern, engage in physical activity, achieve and maintain a healthy body weight, cease tobacco use, and continue statin therapy to reduce their risk of ASCVD events.
    7. For individuals taking any dose of statins, it is reasonable to use caution in individuals > 75 years of age, as well as in individuals who are taking concomitant medications that alter drug metabolism, taking multiple drugs, or taking drugs for conditions that require complex medication regimens (eg, those who have undergone solid organ transplantation or are receiving treatment for HIV). A review of the manufacturer’s prescribing information may be useful before initiation of any cholesterol-lowering drug. 
    8. It is reasonable to evaluate and treat muscle symptoms, including pain, tenderness, stiffness, cramping, weakness, or fatigue in statin-treated patients according to the following management algorithm:
      1. To avoid unnecessary discontinuation of statins, obtain a history prior to current muscle symptoms to establish a baseline before initiation of statin therapy.
      2. If unexplained, severe muscle symptoms or fatigue develop during statin therapy, promptly discontinue the statin and address the possibility of rhabdomyolysis by evaluating CK and creatinine and performing urinalysis for myoglobinuria.
      3. If mild to moderate muscle symptoms develop during statin therapy:
        1. Discontinue the statin until the symptoms can be evaluated.
        2. Evaluate the patient for other conditions that might increase the risk for muscle symptoms (eg, hypothyroidism, reduced renal or hepatic function, rheumatologic disorders such as polymyalgia rheumatic, steroid myopathy, vitamin D deficiency, or primary muscle diseases).
        3. If muscle symptoms resolve, and if no contraindication exists, give the patient the original or a lower dose of the same statin to establish a causal relationship between the muscle symptoms and statin therapy.
        4. If a causal relationship exists, discontinue the original statin. Once muscle symptoms resolve, use a low dose of a different statin.
        5. Once a low dose of a statin is tolerated, gradually increase the dose as tolerated.
        6. If, after 2 months without statin treatment, muscle symptoms or elevated CK levels do not resolve completely, consider other causes of muscle symptoms listed above.
        7. If persistent muscle symptoms are determined to arise from a condition unrelated to statin therapy, or if the predisposing condition has been treated, resume the stain at the original dose. 
    9. For individuals presenting with a confusional state or memory impairment while on statin therapy, it may be reasonable to evaluate the patient for nonstatin causes, such as exposure to other drugs, as well as for systemic and neuropsychiatric causes, in addition to the possibility of adverse effects associated with statin drug therapy. 
  2. Nonstatin Safety Recommendations
    1. Safety of niacin
      1. Baseline hepatic transaminases, fasting blood glucose or hemoglobin A1c, and uric acid should be obtained before initiation of niacin, and again during up-titration to a maintenance dose and every 6 months thereafter.
      2. Niacin should not be used if:
        1. Hepatic transaminase elevations are higher than 2 to 3 times ULN.
        2. Persistent severe cutaneous symptoms, persistent hyperglycemia, acute gout, or unexplained abdominal pain or gastrointestinal symptoms occur. 
        3. New-onset atrial fibrillation or weight loss occurs.
      3. In individuals with adverse effects from niacin, the potential for ASCVD benefits and the potential for adverse effects should be reconsidered before reinitiation of niacin therapy.
      4. To reduce the frequency and severity of adverse cutaneous symptoms, it is reasonable to:
        1. Start niacin at a low dose and titrate to a higher dose over a period of weeks as tolerated.
        2. Take niacin with food or premedicate with aspirin 325 mg 30 minutes before niacin dosing to alleviate flushing symptoms.
        3. If an extended-release preparation is used, increase the dose of extended-release niacin from 500 mg to a maximum of 2000 mg/day over 4-8 weeks, with the dose of extended-release niacin increasing not more than weekly.
        4. If immediate-release niacin is chosen, start a dose of 100 mg 3 times daily and up-titrate to 3 g/day, divided into 2 or 3 doses.
    2. Safety of BAS
      1. Bile acid sequestrants (BAS) should not be used in individuals with baseline fasting triglyceride levels ≥ 300 mg/dL or type III hyperlipoproteinemia, because severe triglyceride elevations might occur. (A fasting lipid panel should be obtained before BAS is initiated, 3 months after initiation, and every 6 - 12 months thereafter.)
      2. It is reasonable to use BAS with caution if baseline triglyceride levels are 250 - 299 mg/dL, and evaluate a fasting lipid panel in 4 - 6 weeks after initiation. Discontinue the BAS if triglycerides exceed 400 mg/dL/
    3. Safety of cholesterol-absorption inhibitors
      1. It is reasonable to obtain baseline hepatic trasaminases before initiation of ezetimibe. When ezetimibe is coadministered with a statin, monitor transaminase levels as clinically indicated, and discontinue ezetimibe if persistent ALT elevations ≥ 3 times ULN occur.
    4. Safety of fibrates
      1. Gemfibrozil should not be initiated in patients on statin therapy because of an increased risk for muscle symptoms and rhabdomyolysis. 
      2. Fenofibrate may be considered concomitantly with a low- or moderate intensity statin only if the benefits from atherosclerotic cardiovascular disease (ASCVD) risk reduction or triglyceride lowering when triglycerides are ≥ 500 mg/dL are judged to outweigh the potential risk for adverse effects.
      3. Renal status should be evaluated before fenofibrate initiation, within 3 months after initiation, and every 6 months thereafter. Assess renal safety with both a serum creatinine level and an estimated glomerular filtration rate (eGFR) based on creatinine.
        1. Fenofibrate should not be used if moderate or severe renal impairment, defined as eGFR < 30 mL/min per 1.73 m2, is present.
        2. If eGFR is between 30 and 59 mL/min per 1.73 m2, the dose of fenofibrate should not exceed 54 mg/day.
        3. If, during follow-up, the eGFR decreases persistently to ≤ 30 mL/min per 1.73 m2, fenofibrate should be discontinued.
    5. Safety of omega-3 fatty acids 
      1. If eicosapentaenoic acid (EPA) and/or docosahexaenoic acid (DHA) are used for the management of severe triglyceridemia, as triglycerides ≥ 500 mg/dL, it is reasonable to evaluate the patient for gastrointestinal disturbances, skin changes, and bleeding. 

How can I use these guidelines to help my patients? 
Registered dietitian nutritionists (RDNs) can use these guidelines to help patients evaluate the risks and benefits for medications for cardiovascular disease (CVD).

References and recommended readings
Stone N, Jennifer R, Lichtenstein A, et al. 2013 ACC/AHA guideline on the treatment of blood cholesterol to reduce atherosclerotic Cardiovascular risk in adults. Circulation. 2013; 129:S1-S45. doi:10.1161/01.cir.9999437738.63853.7a.