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CLINICAL STATEMENTS AND GUIDELINES

August 29, 2023 Circulation. 2023;148:e9–e119. DOI: 10.1161/CIR.0000000000001168

Virani et al 2023 AHA/ACC/ACCP/ASPC/NLA/PCNA Chronic Coronary Disease Guideline

Cost Value Statement: Intermediate Value B-NR 3.	 In patients with CCD and type 2 diabetes,

addition of an SGLT2 inhibitor at US prices is projected to be of intermediate value compared with standard of care.18

1 A 4 In patients with CCD and heart failure with

LVEF ≤40%, use of an SGLT2 inhibitor is recommended to reduce the risk of cardiovascular death and heart failure hospitalization19–22 and to improve QOL,23,24 irrespective of diabetes status.*

Cost Value Statement: Intermediate Value B-NR 5 In patients with CCD and heart failure with

LVEF ≤40%, addition of an SGLT2 inhibitor to GDMT, irrespective of diabetes status, is projected to be of intermediate value at US prices.25,26

2a B-R 6 In patients with CCD and heart failure with

LVEF >40%, use of an SGLT2 inhibitor can be beneficial in decreasing heart failure hospitalizations27,28 and to improve QOL,4,29 irrespective of diabetes status.

Cost Value Statement: Intermediate Value B-NR 7 In patients with CCD and heart failure with

LVEF >40%, addition of an SGLT2 inhibitor to GDMT, irrespective of diabetes status, is projected to be of uncertain value at US prices.30

*Modified from the 2022 AHA/ACC/HFSA Guideline for the Management of Heart Failure.31

Synopsis Comprehensive cardiovascular risk reduction strategies are effective in patients with CCD and type 2 diabetes.32 Despite these efforts, cardiovascular event rates remain high among patients with type 2 diabetes, even among well-managed patients,1,10,33 and CAD remains the leading cause of morbidity and death.34 Two classes of glucose-lowering medications (SGLT2 inhibitors and GLP-1 receptor agonists) have potent cardiovascular benefits, independent of their effects on glycemic control.1,3,4,9,10,13 Both medications improve glycemic control, facilitate weight loss, reduce progression of kidney disease, and reduce the risk of cardiovascular events through distinct pathways. Yet their adoption in clinical practice has been slow,35,36 highlighting an opportunity for cardiovascular specialists to have a greater collaborative role in the care of patients with CCD and type 2 diabetes.37 Comprehensive risk factor control should include lifestyle modifications38 and GDMT to optimize dyslipidemia (Section 4.2.6, “Lipid Management”), hypertension (Section 4.2.7, “Blood Pressure Management”), weight management (Section 4.2.9), nutrition (Section 4.2.1), physical activity (Section 4.2.11), and hyperglycemia.39 Regarding glucose control, the American Diabetes Association recommends a hemoglobin A1C goal of <7%40 and a more conservative glycemic target (eg, hemoglobin A1c <8% or 8.5%) for those older (>65 years of age) with CCD and type 2 diabetes or comorbidities,41 to limit the risk of hypoglycemia.40–48 Among patients with CCD and type 2 diabetes, a patient-centered approach (Section 4.1.1, “Team-Based Approach”) should guide shared decision-making (Section 4.1.3) about glycemic targets and the decision to initiate an SGLT-2 inhibitor, GLP-1 receptor agonist, or both.39

Recommendation-Specific Supportive Text

1 In patients with CCD and type 2 diabetes, both

SGLT2 inhibitors and GLP-1 receptor agonists significantly reduce the risk of MACE, with additional benefits in terms of weight loss49 and progression of kidney disease.7,16,17 SGLT2 inhibitors do not appear to primarily reduce atherosclerosis as much as they reduce incident and worsening HF (for which patients with CCD and type 2 diabetes who are at risk).1–8 In contrast, GLP-1 receptor agonists appear to primarily reduce the risk of atherosclerotic events, such as MI and stroke. Although there has been some inconsistency across the cardiovascular outcomes trials,9–15 meta-analyses have shown no statistically significant heterogeneity in cardiovascular risk reduction across different GLP-1 receptor agonists.16,17 Currently, no compelling evidence is available that either medication reduces cardiovascular risk in patients with CCD but without type 2 diabetes,50,51 or in the case of SGLT2 inhibitors, without concomitant HF. Given their distinct mechanisms, the cardiovascular risk reduction may be greater using both classes of medications compared with either medication alone. Data on concurrent use are mostly limited to safety and metabolic endpoints,52 but available studies showed benefit in BP and weight reduction with dual therapy.53,54 Whether the effects on cardiovascular outcomes are additive, or even synergistic, is not yet known. 2.	 In a systematic review of cost-effectiveness analyses examining the addition of GLP-1 agonists compared with alternative therapies (including insulin or other classes of diabetes medications) among patients with diabetes, the use of a GLP-1 agonist is projected to be of high value (costsaving or incremental cost-effectiveness ratio of <$50 000 per QALY gained).18 Although these analyses were performed in all patients with type 2 diabetes rather than specifically in patients with CCD, these results appear to be robust to a range of assumptions regarding underlying risk and are likely applicable to patients with CCD. 3.	 In a systematic review of cost-effectiveness analy-

ses examining the addition of SGLT2 inhibitors to standard of care among patients with diabetes, the use of an SGLT2 inhibitor is projected to be of intermediate value ($50 000 to <$150 000 per QALY gained) compared with standard of care.18 As

Recommendations for Use of SGLT2 Inhibitors and GLP-1 Receptor Agonists (Continued )

COR LOE Recommendations

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