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Canadian Pharmacists Association
Canadian Pharmacists Association
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Chapter 28: Treatment of Diabetes in People with Heart Failure

Canadian Diabetes Association 2013 Clinical Practice Guidelines for the Prevention and Management of Diabetes in Canada

Introduction
  • Type 2 diabetes often occurs in association with other cardiovascular risk factors, such as hypertension, dyslipidemia, smoking and obesity, which together are strongly associated with atherosclerosis, ischemic heart disease and left ventricular (LV) dysfunction.
  • LV dysfunction can be clinically silent or associated with the typical clinical signs and symptoms of heart failure (e.g. peripheral edema, shortness of breath, fatigue), although the elderly may have atypical symptoms.
  • These symptoms need to be differentiated from other conditions that may have similar presentations, such as chronic obstructive pulmonary disease, pneumonia, anemia, varicose veins, depression, etc.
Heart Failure in People with Diabetes
  • The diagnosis of heart failure is made by association of typical clinical signs and symptoms with objective evidence, such as information obtained from a chest x-ray, an echocardiogram or plasma natriuretic peptide testing (brain natriuretic peptide [BNP] and prohormone of BNP [NT-pro-BNP]).
  • Diabetes is associated with increased prevalence of heart failure, both systolic (commonly defined as LVEF <40%) and diastolic (commonly defined as LVEF >50%, but also referred to as preserved systolic function or preserved EF). However, the overlap between systolic and diastolic heart failure is considerable, and many people have a combination of systolic and diastolic dysfunction, although one is often reported to be predominant. Current tests, such as echocardiography, usually fully characterize all aspects of systolic and diastolic dysfunction in individuals.
  • It is recognized that diabetes can cause heart failure independently of ischemic heart disease by causing a diabetic cardiomyopathy.
  • Epidemiological studies have shown that the incidence of heart failure is 2- to 4-fold higher in people with diabetes compared to those without diabetes.
  • Additionally, studies have shown the occurrence of asymptomatic abnormalities of ventricular systolic and diastolic function, independently from ischemic heart disease or systemic hypertension.
  • While an increase in glycated hemoglobin (A1C) among individuals with diabetes is a recognized risk factor for heart failure, no prospective study to date has demonstrated that improved glycemic control significantly reduces the incidence of heart failure.
  • Microalbuminuria is also an independent risk factor for heart failure, especially in people with diabetes. Increasing urinary albumin-to-creatinine ratio is associated with a stepwise increase (2- to 4-fold) in the risk of heart failure development.
    • Angiotensin-converting enzyme (ACE) inhibitors significantly reduce urinary albumin excretion and have been shown to lower the risk of new-onset heart failure in patients with CVD or diabetes.
  • Beta blockers should be prescribed when indicated for systolic heart failure, as they provide similar benefits in people with diabetes compared with people without diabetes [Grade B, Level 2].
    • Three beta blockers have been shown to reduce morbidity and mortality for patients with heart failure and diabetes: carvedilol, bisoprolol and metoprolol.
    • Data to date suggest overall glycemic control for these patients improves as their heart failure syndrome improves on therapy.
    • Carvedilol, in comparison to other beta blockers, has been shown to be associated with improved glycemic control. In addition, some data suggest the improvement in LVEF is also greater with carvedilol. For this reason, some clinicians prefer carvedilol as the beta blocker of choice in such patients.
Treatment of Individuals with Both Diabetes and Heart Failure
  • Individuals with diabetes and heart failure should receive the same heart failure therapies as those identified in the evidence-based Canadian Cardiovascular Society heart failure recommendations [Grade D, Consensus].
  • However, patients with diabetes have more comorbidities and are at increased risk for development of hyperkalemia and worsening renal dysfunction in the setting of renin-angiotensin-aldosterone (RAAS) blocking agents.
  • In people with diabetes and heart failure and an estimated glomerular filtration rate <60 mL/min, or if combined renin-angiotensin-aldosterone blockade is employed:
    • Starting doses of angiotensin-converting enzyme inhibitors or angiotensin receptor II antagonists (angiotensin receptor blockers) should be halved [Grade D, Consensus].
    • Serum electrolytes and creatinine, blood pressure and body weight, as well as heart failure symptoms and signs, should be monitored within 7–10 days of any initiation or titration of therapy [Grade D, Consensus].
    • Dose-up titration should be more gradual (with monitoring of blood pressure, serum potassium and creatinine) [Grade D, Consensus].
    • The target drug doses should be the same as those identified in the evidence-based Canadian Cardiovascular Society recommendations on heart failure, if well tolerated [Grade D, Consensus].
Metformin
  • Metformin is an effective oral antihyperglycemic agent, but based on isolated case reports and a biochemical rationale for a risk of lactic acidosis, it is approved for use under a warning in the setting of several conditions, including heart failure.
    • Meta-analyses have evaluated the occurrence of lactic acidosis with the use of metformin (over 70 000 patient-years) and have shown no increase in lactic acidosis.
    • Cardiovascular outcomes in heart failure patients taking metformin were better than in those taking other antihyperglycemic agents.
    • The current evidence suggests that patients with heart failure fare at least as well, if not better, with metformin than with other antihyperglycemic agents if they have only mild-to-moderate renal dysfunction (estimated glomerular filtration rate >30 mL/min).
  • Therefore metformin should still be considered as first-line therapy in heart failure patients with mild-to-moderate renal dysfunction.

For definitions of the levels of evidence cited in this chapter, please refer to the Guideline Recommendations: Levels of Evidence.

If you would like more details on this topic, please visit the Canadian Diabetes Association Clinical Practice Guidelines: Chapter 28.