2018 Cholesterol Clinical Practice Guidelines: Synopsis of the 2018 American Heart Association/American College of Cardiology/Multi society Cholesterol Guideline

2018 Cholesterol Clinical Practice Guidelines: Synopsis of the 2018 American Heart Association/American College of Cardiology/Multi society Cholesterol Guideline

CLINICAL GUIDELINES |4 JUNE 2019 Annals Of Internal Medicine

According to the Centers for Disease Control and Prevention, heart disease is the leading cause of death in the United States, including for African American, Hispanic, and white persons (1) and for both women and men. The leading cause of death attributable to cardiovascular disease (CVD) in the United States is coronary heart disease (43.8%), followed by stroke (16.8%)—the 2 components of fatal atherosclerotic CVD (ASCVD) (2). The economic impact of ASCVD is large: It accounted for 14% of total health expenditures in 2013 to 2014, more than any major diagnostic group.

The American Heart Association and American College of Cardiology (AHA/ACC), with the support of 10 collaborating organizations, have recently released their 2018 cholesterol guideline (3). In addition, they have released a companion special report on the use of risk assessment tools to guide decision making in primary prevention 


The guideline endorses a heart-healthy lifestyle beginning in childhood to reduce lifetime risk for ASCVD. It contains several new features compared with the 2013 guideline. For secondary prevention, patients at very high risk may be candidates for adding nonstatin medications (ezetimibe or proprotein convertase subtilisin/kexin type 9 [PCSK9] inhibitors) to statin therapy. In primary prevention, a clinician–patient risk discussion is still strongly recommended before a decision is made about statin treatment. The AHA/ACC risk calculator first triages patients into 4 risk categories. Those at intermediate risk deserve a focused clinician–patient discussion before initiation of statin therapy. Among intermediate-risk patients, identification of risk-enhancing factors and coronary artery calcium testing can assist in the decision to use a statin. Compared with the 2013 guideline, the new guideline gives more attention to percentage reduction in low-density lipoprotein cholesterol as a treatment goal and to long-term monitoring of therapeutic efficacy. To simplify monitoring, nonfasting lipid measurements are allowed.

Synopsis of Recommendations

1. Healthy lifestyle over the lifespan. A healthy lifestyle reduces ASCVD risk at all ages. In younger persons, healthy lifestyle can reduce development of risk factors, can prevent the need for subsequent statin use, and is foundational therapy for ASCVD risk reduction. In young adults aged 20 to 39 years, an assessment of lifetime risk facilitates the clinician–patient risk discussion and emphasizes intensive lifestyle efforts. In all age groups, lifestyle therapy is the primary intervention for metabolic syndrome.

2. Use of maximally tolerated doses of statins in secondary prevention of ASCVD. In patients with clinical ASCVD, the guideline recommends reduction of low-density lipoprotein cholesterol (LDL-C) levels with high-intensity or maximally tolerated statin therapy. The more LDL-C is reduced during statin therapy, the greater the subsequent risk reduction will be. High-intensity statins typically reduce LDL-C levels by an average of at least 50%, which is an attainable goal in most patients with ASCVD.

3. Use of nonstatin medications in addition to statin therapy for patients at very high risk for ASCVD. Very high risk is defined as a history of multiple major ASCVD events, or 1 major ASCVD event and multiple other high-risk conditions. In very-high-risk ASCVD, the guideline recommends an LDL-C threshold of 1.8 mmol/L (70 mg/dL) as reasonable for adding a nonstatin medication (ezetimibe or proprotein convertase subtilisin/kexin type 9 [PCSK9] inhibitors) to maximally tolerated statin therapy. In patients who had very high risk, had a baseline LDL-C level of approximately 1.8 mmol/L (70 mg/dL), and were receiving statin therapy, addition of ezetimibe reduced risk for major events by 2 percentage points (6). Two RCTs recruited patients at very high risk who were receiving maximally tolerated doses of statins, had LDL-C levels greater than 1.8 mmol/L (70 mg/dL) (average, about 2.3 mmol/L [90 mg/dL]), and were treated with PCSK9 inhibitors for approximately 3 years (7, 8). Addition of PCSK9 inhibitors reduced risk for subsequent ASCVD events by about 15%. On the basis of these RCTs, the guideline states that addition of ezetimibe to maximally tolerated statin therapy is reasonable when LDL-C levels are 1.8 mmol/L (70 mg/dL) or higher. In patients at very high risk whose LDL-C levels remain above this threshold while they receive maximally tolerated statin and ezetimibe therapy, the guideline suggests that a PCSK9 inhibitor is a reasonable addition, although long-term safety (>3 years) is uncertain and cost-effectiveness was low at mid-2018 list prices. Some prescription programs have recently been initiated to reduce the cost of PCSK9 inhibitors. As cost decreases, cost-effectiveness will increase (9).

4. Severe primary hypercholesterolemia, often starting in childhood. In patients with primary, severe hypercholesterolemia (LDL-C level ≥4.9 mmol/L [≥190 mg/dL]), calculating 10-year ASCVD risk is not necessary. Maximally tolerated statin therapy is required to reduce LDL-C levels toward a lower risk range. If the LDL-C level remains at or above 2.6 mmol/L (100 mg/dL), adding ezetimibe is reasonable. If the patient still has an LDL-C level above this threshold while receiving a statin plus ezetimibe and has multiple factors that increase subsequent risk for ASCVD events, a PCSK9 inhibitor may be considered, although long-term safety (>3 years) is uncertain and economic value is low based on list prices from mid-2018.

5. Adults aged 40 to 75 years with diabetes mellitus and an LDL-C level of 1.8 mmol/L (70 mg/dL) or higher. In these patients, the guidelines recommend starting moderate-intensity statin therapy without the need to calculate 10-year ASCVD risk. In patients with diabetes and higher risk, especially those who have multiple risk factors or are aged 50 to 75 years, use of a high-intensity statin is reasonable to reduce the LDL-C level by at least 50%.

6. Clinician–patient risk discussion. In adults aged 40 to 75 years who are evaluated for primary ASCVD prevention, the guidelines continue to recommend a clinician–patient risk discussion before statin therapy is started. Risk discussion should include review of major risk factors (such as cigarette smoking and elevated levels of blood pressure, LDL-C, hemoglobin A1c level [if indicated], or calculated 10-year risk for ASCVD), risk-enhancing factors (see recommendation 8), the potential benefits of lifestyle and statin therapies, the potential for adverse effects and drug–drug interactions, consideration of costs of statin therapy, and patient preferences and values in shared decision making.

7. Adults aged 40 to 75 years without diabetes mellitus who have LDL-C levels of at least 1.8 mmol/L (70 mg/dL), and a 10-year ASCVD risk of 7.5% or higher. In this population, the guidelines recommend moderate-intensity statin therapy if a discussion of treatment options favors statins. Patients without ASCVD are categorized and stratified for risk by age, coexisting conditions, and risk factors (Figure). When those with diabetes or LDL-C levels above 4.9 mmol/L (190 mg/dL) are excluded, RCT evidence for the benefit of statin therapy in persons aged 40 to 75 years continues to accumulate (10). Patients in this age range are triaged into 4 categories of 10-year risk for ASCVD: low (<5%), borderline (5% to 7.4%), intermediate (7.5% to 19.9%), and high (≥20%). In the latter category, the guideline recommends high-intensity statin therapy because of its proven benefit. Evidence from RCTs supports the efficacy of statin therapy for patients whose 10-year risk is 5% or higher. Nonetheless, in those with borderline or intermediate risk, clinical judgment is required to initiate statin treatment on the basis of risk–benefit considerations and patient preferences.

8. Decision making in primary prevention in adults aged 40 to 75 years. The guideline endorses a 3-tiered decision process for treatment in adults aged 40 to 75 years with borderline (5% to 7.4%) or intermediate (7.5% to 19.9%) risk for ASCVD. The decision process begins with estimation of 10-year risk. As in prior guidelines, 10-year risk of 7.5% or higher does not result in automatic statin assignment. To personalize risk, the current guideline recommends evaluation of risk-enhancing factors—that is, stable factors that associate with ASCVD beyond the major risk factors incorporated into the risk calculator. These include family history of premature ASCVD; LDL-C levels of 4.1 mmol/L (160 mg/dL) or higher; metabolic syndrome; chronic kidney disease; history of preeclampsia or premature menopause (in women); chronic inflammatory disorders; high-risk ethnicity, such as South Asian ancestry; triglyceride levels persistently elevated above 2.0 mmol/L (175 mg/dL); and, if measured, elevations in apolipoprotein B (may be especially useful if hypertriglyceridemia >2.3 mmol/L [>200 mg/dL] persists), high-sensitivity C-reactive protein levels of 19.0476 nmol/L (2.0 mg/L) or higher, lipoprotein(a) levels with elevations above 125 nmol/L (50 mg/dL) (especially useful in those with a family history of premature ASCVD), or reduced ankle–brachial index. Presence of risk-enhancing factors in patients at intermediate risk favors statin therapy. In addition, if risk status remains uncertain, measurement of coronary artery calcium (CAC) can be considered.

9. CAC scoring to improve risk stratification. In adults who do not have diabetes, are aged 40 to 75 years, have LDL-C levels of 1.8 to 4.9 mmol/L (70 to 189 mg/dL), and have a 10-year risk of 7.5% to 19.9% as estimated by the pooled cohort equations (PCEs), but who are uncertain about statin benefit, CAC scoring may help resolve the uncertainty. If the CAC score is 0 Agatston units, statin therapy may be withheld or delayed, except in cigarette smokers and those with a strong family history of premature ASCVD or diabetes. A CAC score of 1 to 99 units favors statin therapy, especially in patients older than 55 years. For any patient, if the CAC score is at least 100 Agatston units or is at or above the 75th percentile, statin therapy is indicated unless otherwise deferred by the outcome of a clinician–patient risk discussion.

10. Follow-up for adherence and adequacy of response. The current guideline continues to recommend assessment of adherence to medications and lifestyle and percentage change in LDL-C level at 4 to 12 weeks after statin initiation or dosage adjustment; this assessment should be repeated every 3 to 12 months as needed. Clinicians may often underestimate adherence unless specific questions are asked (11).

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