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Arnett et al 2019 ACC/AHA Guideline on the Primary Prevention of Cardiovascular Disease

September 10, 2019 Circulation. 2019;140:e596–e646. DOI: 10.1161/CIR.0000000000000678 e612

CLINICAL STATEMENTS AND GUIDELINES leading to a reduction in hyperglycemia in adults with T2DM. In a substudy of the UKPDS (United Kingdom Prospective Diabetes Study), metformin, compared with conventional therapy (ie, lifestyle modifications alone), resulted in a 32% reduction in microvascular and macrovascular diabetesrelated outcomes, a 39% reduction in MI, and a 36% reduction in all-cause mortality rate.S4.2-5 A 2016 systematic review and meta-analysis of glucose-lowering therapies for T2DM supported the use of metformin as first-line therapy for T2DM because of its beneficial effects on HbA1c, weight, and improved ASCVD outcomes (compared with sulfonylureas), as well as its acceptable safety profile and low cost. However, a separate systematic review found no evidence of reduced CVD events or CVD deaths with metformin.S4.2-8 Metformin carries a small risk of lactic acidosis and must be used with caution in patients with CKD. For younger individuals or those with a mildly elevated HbA1c at the time of diagnosis of T2DM, clinicians can consider a trial of lifestyle therapies for 3 to 6 months before reconsideration of metformin. 4.	Several classes of medications have been shown to effectively lower blood glucose but may or may not affect ASCVD risk.S4.2-23–S4.2-26 However, 2 classes of glucose-lowering medications have recently been demonstrated to reduce CVD events in adults with T2DM and high ASCVD risk. SGLT-2 inhibitors act in the proximal tubule to increase urinary excretion of glucose and sodium, leading to a reduction in HbA1c, body weight, and BP. Three RCTs have shown a significant reduction in ASCVD events and heart failure with use of an SGLT-2 inhibitor.S4.2-9,S4.2-10,

S4.2-12 Although most patients studied had established CVD at baseline, the reduction in heart failure has been shown to extend to primary prevention populations.S4.2-12,S4.2-27 The GLP-1R agonists increase insulin and glucagon production in the liver, increase glucose uptake in muscle and adipose tissue, and decrease hepatic glucose production. Three GLP-1R agonists have been found to significantly reduce the risk of ASCVD in adults with T2DM who are at high ASCVD risk.S4.2-11,S4.2-13,S4.2-14 As opposed to a reduction in heart failure with SGLT-2 inhibitors, the benefit of the GLP-1R agonists has been a reduction in ASCVD events though the majority of patients studied had established CVD. In patients with T2DM and additional risk factors for CVD, it may be reasonable to initiate these 2 classes of medications for primary prevention of CVD.

4.3 Adults With High Blood Cholesterol

Recommendations from the 2018 Cholesterol Clinical Practice GuidelinesS4.3-1 are included and adapted below. Recommendations for Adults With High Blood Cholesterol

Referenced studies that support recommendations are summarized in Online Data Supplements 11 and 12.

COR LOE Recommendations

I A 1.  In adults at intermediate risk (≥7.5% to <20% 10-year ASCVD risk), statin therapy reduces risk of ASCVD, and in the context of a risk discussion, if a decision is made for statin therapy, a moderate-intensity statin should be recommended.S4.3-2–S4.3-9

Adapted from recommendations in the 2018 Cholesterol Clinical Practice Guidelines.S4.3-1

I A 2.  In intermediate risk (≥7.5% to <20% 10-year ASCVD risk) patients, LDL-C levels should be reduced by 30% or more, and for optimal ASCVD risk reduction, especially in patients at high risk (≥20% 10-year ASCVD risk), levels should be reduced by 50% or more.S4.3-2,S4.3-5–S4.3-10

Adapted from recommendations in the 2018 Cholesterol Clinical Practice Guidelines.S4.3-1

I A 3.  In adults 40 to 75 years of age with diabetes, regardless of estimated 10-year ASCVD risk, moderate-intensity statin therapy is indicated.S4.3-11–S4.3-19

Included from recommendations in the 2018 Cholesterol Clinical Practice Guidelines.S4.3-1

I B-R 4.  In patients 20 to 75 years of age with an LDL-C level of 190 mg/dL (≥4.9 mmol/L) or higher, maximally tolerated statin therapy is recommended.S4.3-2,S4.3-20–S4.3-25

Included from recommendations in the 2018 Cholesterol Clinical Practice Guidelines.S4.3-1

IIa B-R 5.  In adults with diabetes mellitus who have multiple ASCVD risk factors, it is reasonable to prescribe high-intensity statin therapy with the aim to reduce LDL-C levels by 50% or more.S4.3-2,S4.3-7

Included from recommendations in the 2018 Cholesterol Clinical Practice Guidelines.S4.3-1

IIa B-R 6.  In intermediate-risk (≥7.5% to <20% 10year ASCVD risk) adults, risk-enhancing factors favor initiation or intensification of statin therapy.S4.3-7,S4.3-26–S4.3-33

Adapted from recommendations in the 2018 Cholesterol Clinical Practice Guidelines.S4.3-1

IIa B-NR 7.  In intermediate-risk (≥7.5% to <20% 10-year ASCVD risk) adults or selected borderline-risk (5% to <7.5% 10-year ASCVD risk) adults in whom a coronary artery calcium score is measured for the purpose of making a treatment decision, AND

If the coronary artery calcium score is zero, it is reasonable to withhold statin therapy and reassess in 5 to 10 years, as long as higher-risk conditions are absent (eg, diabetes, family history of premature CHD, cigarette smoking); If coronary artery calcium score is 1 to 99, it is reasonable to initiate statin therapy for patients ≥55 years of age; If coronary artery calcium score is 100 or higher or in the 75th percentile or higher, it is reasonable to initiate statin therapy.S4.3-28,S4.3-34 Adapted from recommendations in the 2018 Cholesterol Clinical Practice Guidelines.S4.3-1

IIb B-R 8.  In patients at borderline risk (5% to <7.5% 10year ASCVD risk), in risk discussion, the presence of risk-enhancing factors may justify initiation of moderate-intensity statin therapy.S4.3-28,S4.3-35

Adapted from recommendations in the 2018 Cholesterol Clinical Practice Guidelines.S4.3-1

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