Optimizing Risk Factors and Management of Chronic Coronary Artery Disease in Patients with Type 2 Diabetes

Cardiovascular disease remains the leading cause of morbidity and mortality among patients with diabetes mellitus, highlighting the importance of optimal risk factor modification and choosing management strategies that reduces the risk of cardiovascular events^{1, 2}. In fact, patients with diabetes experience an up to 50 % increased risk of cardiovascular-related death³. In addition to increased risk of cardiovascular events, presence of diabetes has the potential to influence treatment choices for those with established coronary artery disease (CAD) including medications and revascularization strategies. Current evidence suggests that the mechanism by which glycemic control is achieved in diabetes also has a substantial impact on cardiovascular outcomes^4-6. The cardiovascular specialist of today needs both to consider presence of diabetes in treatment decisions and potentially help direct the choice of optimal glucose-lowering drugs.

Given the importance of diabetes as a risk factor for cardiovascular diseases and its implications for management, a recent Scientific Statement from the American Heart Association authored by Arnold et al summarize effective, patient-centered management of coronary artery disease in patients with diabetes mellitus based on contemporary evidence⁷. This is indeed timely given a recent resurgence of diabetes complications particularly among young and middle-aged adults⁸. This scientific statement provides helpful guidance to cardiologists on effective risk reduction strategies and the role of glycemic management including choice of therapies in improving cardiovascular outcomes.

Antiplatelet therapy remains a cornerstone in secondary preventive care in diabetes mellitus, and given concerns about aspirin resistance in this population and availability of generic clopidogrel, clopidogrel as an alternative to aspirin may be considered for secondary prevention in patients with diabetes mellitus. Long-term therapy with clopidogrel in addition to aspirin may also be considered in select patients with stable CAD and diabetes, balancing lower ischemic risks with increasing bleeding risks and may be particularly useful in those with prior myocardial infarction, younger age, and tobacco use. The presence of hypertension in patients with diabetes mellitus significantly increases the risk of myocardial infarction, stroke, and all-cause mortality and optimal blood pressure control is indicated9. As such, while all patients with type 2 diabetes and coronary artery disease certainly benefit from a blood pressure of <140/90 mmHg, lower blood pressure targets of <130/80 mmHg are appropriate for many patients, particularly those at higher risk of stroke (e.g., black and Asian patients, those with cerebrovascular disease) and other microvascular complications such as chronic kidney disease. Regarding choice of drugs, angiotensin converting enzyme (ACE) inhibitors/angiotensin receptor blockers (ARB) should be considered first-line for the treatment of hypertension in patients with diabetes mellitus. Beta-blockers are less preferred as antihypertensive agents in patients with diabetes and should be considered for patients with clear indications such as angina or to those who require additional blood pressure lowering beyond ACE or ARB.

Randomized trial data have established the benefits of statin therapy in the primary and secondary prevention of CAD in patients with diabetes mellitus. Studies have also demonstrated that statins are associated with a small but significantly increased risk of incident diabetes mellitus, therefore it is important to assure patients that despite a potential modest increase in blood sugars, the risk-benefit ratio is strongly in favor of statins in those with diabetes mellitus and CAD. Additional drugs may be needed for LDL-C lowering in high risk patients with diabetes and CAD particularly when LDL-C levels are >70 mg/dL despite maximally tolerated statin, the addition of non-statin LDL-C lowering therapies, such as ezetimibe and PCKS9 inhibitors, may be considered based on the individual’s overall risk profile, personal preferences, and drug access.

While drug therapies are important for risk reduction in individual with diabetes mellitus, lifestyle modifications such as smoking cessation, heart-healthy diet, maintaining optimal weight loss, sleep and stress management, and regular exercise/physical activity, is key foundation of clinical care both for patients with diabetes mellitus and those with CAD. The American Diabetes Association (ADA) guidelines recommend that patients interrupt prolonged sitting with light activity every 30 minutes and engage in at least 150 minutes/week of moderate- to-vigorous physical activity¹⁰.

Regarding glycemic control, the ADA Standards of Medical Care recommend a reasonable HbA1c goal for many non- pregnant adults at HbA1c <7%¹¹. The intense efforts needed to achieve an HbA1c <7% for patients with diabetes increase the risks associated with polypharmacy, contribute to treatment burden (including financial burden), and may increase the risk of hypoglycemia without clear cut benefits^{12, 13}. Furthermore, it is evident that that while glucose lowering itself has only modest effect on cardiovascular events, the method by which glucose is lowered has significant impact. A consensus report from the ADA and European Association for the Study of Diabetes (EASD) as well as an Expert Consensus Decision Pathway from the American College of Cardiology recommends use of either a Glucagon-like peptide-1 (GLP-1) receptor agonist or sodium-glucose cotransporter-2 (SGLT-2) inhibitor to improve cardiovascular outcomes in patients with high cardiovascular risk regardless of HbA1c^14-16. SGLT-2 inhibitor should be preferred in those with heart failure or chronic kidney disease¹.

For management of CAD in patients with diabetes mellitus, an individualized, patient-centric multidisciplinary heart team approach to revascularization strategy is indicated taking into account coronary anatomy, risk profile, presentation features, and patient preference with the understanding that CABG with concomitant optimal medical therapy offers improved outcomes in the majority of patients with diabetes mellitus and multivessel CAD and is the revascularization strategy recommended by current major society guidelines². With ongoing medical, surgical, and percutaneous therapy there is a need for continuous reassessment of relative risks and benefits associated with these modalities to optimize outcome in individuals with diabetes mellitus.

Much has changed in the recent years in our understanding of the pathophysiology of cardiovascular risk in patients with diabetes mellitus with emergence of glycemic therapies that provide robust glucose control as well as mitigate risk of cardiovascular events. It is important that physicians in general and cardiovascular specialists understand this expanding knowledge base and apply the evidence that can directly improve clinical outcomes in an individual patient.