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Canadian Pharmacists Association
Canadian Pharmacists Association
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Chapter 26: Management of Acute Coronary Syndromes

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

Incidence and Prognosis
  • Diabetes (together with lipid abnormalities, smoking and hypertension) is 1 of the top 4 independent risk factors for myocardial infarction (MI).
  • Today, approximately 15% to 35% of patients admitted with an acute coronary syndrome (ACS) have known diabetes, and as many as another 15% have undiagnosed diabetes.
  • Compared to individuals without diabetes, patients with diabetes have:
  1. A 3-fold increased risk of ACS
  2. Occurrence of acute coronary events 15 years earlier
  3. A 2-fold increased short- and long-term mortality
  4. An increased incidence of post-infarction recurrent ischemic events, heart failure and cardiogenic shock
  5. A similar benefit from guideline recommended management strategies
  6. Less utilization of guideline recommended care, which may contribute to adverse outcomes in the patient with diabetes
Identification of Diabetes in Patients with ACS
  • More than two-thirds of patients with MI have either diabetes or impaired glucose regulation (impaired glucose tolerance and impaired fasting glucose).
  • Patients with ACS should be screened for diabetes with a fasting blood glucose, glycated hemoglobin (A1C) or 75g OGTT prior to discharge from hospital [Grade D, Consensus]. The frequency of previously unrecognized diabetes in the ACS population is reported to be between 4% and 22%, depending on the test that was used to diagnose diabetes.
Management of ACS in the Patient with Diabetes
  • Guidelines for the management of patients with ACS have been developed by the American College of Cardiology (ACC)/American Heart Association (AHA) and the European Society of Cardiology.
  • In most situations, there are no clinical trials that specifically address management of the patient with diabetes and ACS.  However, all patients with diabetes and ACS should receive the same treatments that are recommended for patients with ACS without diabetes since they benefit equally [Grade D, Consensus].
Antiplatelet Therapy
  • Platelet aggregation plays a central role in the development of the occlusive thrombus responsible for acute coronary occlusion in patients with ACS.
  • Patients with diabetes have a prothrombotic state due to dysfunctional and hyperactive platelets, endothelial dysfunction, elevated coagulation factors and decreased fibrinolysis.
  • Increased platelet activity is due to multiple metabolic and cellular factors associated with diabetes that include endothelial dysfunction, the impact of hyperglycemia and deficient insulin action.
  • Diabetes is associated with an increased incidence of recurrent atherothrombotic events, including stent thrombosis. Antiplatelet therapy has been shown to reduce atherothrombotic events in patients with ACS, both during the acute phase and in the longer term.
  • The beneficial effect of ASA has been shown in multiple clinical trials in patients with non ST-segment elevation (NSTE) ACS and ST-elevation MI (STEMI).
  • Dual antiplatelet therapy with ASA and clopidogrel, administered from the time of presentation has been the recommended standard of care for patients with NSTE ACS
  • Clopidogrel is a relatively weak inhibitor of platelet aggregation with a wide variation of inhibition of in vitro platelet aggregation. There is a higher incidence of events in patients with residual platelet activity, and patients with diabetes have higher residual platelet activity despite ASA and clopidogrel treatment.
  • Two new antiplatelet agents, prasugrel and ticagrelor are now available in Canada, which are more effective and predictable inhibitors of platelet aggregation
  • In the TRITON study, prasugrel was administered at the time of coronary angioplasty in subjects with diabetes. This was associated with greater platelet inhibition and fewer poor responders.  
  • Patients with diabetes and ACS undergoing percutaneous coronary intervention (PCI) should receive antiplatelet therapy with prasugrel (if clopidogrel naïve, <75 years of age, weight >65 kg, and no history of stroke) [Grade A, Level 1] or ticagrelor [Grade B, Level 1], rather than clopidogrel, to further reduce recurrent ischemic events.
  • Patients with diabetes and NSTE ACS and higher-risk features destined for a selective invasive strategy should receive ticagrelor rather than clopidogrel [Grade B, Level 2].
  • Platelet aggregation is largely mediated by the GPIIb/IIIa receptor through its binding to fibrinogen. The GPIIb/IIIa receptor inhibitors abciximab, eptifibatide and tirofiban were shown to be effective for the management of ACS in patients with diabetes

For full information on the studies mentioned above, please refer to Canadian Diabetes Association Clinical Practice Guidelines: Chapter 26.

Glycemic Control
  • Hyperglycemia during the first 24 to 48 hours after admission for ACS is associated with increased early mortality, whether or not the patient has diabetes.
  • In-hospital management of diabetes in ACS should include strategies to avoid both hyperglycemia and hypoglycemia:
    • Blood glucose should be measured on admission and monitored throughout the hospitalization [Grade D, Consensus]
    • Patients with acute MI and blood glucose >11.0 mmol/L on admission may receive glycemic control in the range of 7.0 to 10.0 mmol/L, followed by strategies to achieve recommended glucose targets long term [Grade C, Level 2]. Insulin therapy may be required to achieve these targets [Grade D, Consensus]. A similar approach may be taken in those with diabetes and admission blood glucose ≤11.0 mmol/L [Grade D, Consensus]
      • An appropriate protocol should be developed and staff trained to ensure the safe and effective implementation of this therapy and to minimize the likelihood of hypoglycemia [Grade D, Consensus].
  • Post-ACS long-term glycemic control trials using agents from newer drug classes, such as dual peroxisome proliferator-activated receptor agonist, glucagon-like peptide-1 (GLP-1) receptor agonists, and acarbose, are currently under way
  • A recent meta-analysis of these trials suggested a 17% relative reduction in nonfatal MI in subjects included in the intensive glucose control
    • There was no reduction of all-cause mortality
    • The same meta-analysis indicated the possibility that a greater benefit could be derived from treating patients with recently diagnosed diabetes more intensively.
Revascularization
  • Patients with diabetes and non-STE ACS and high-risk features should receive an early invasive strategy rather than a selective invasive approach to revascularization to reduce recurrent coronary events, unless contraindicated [Grade B, Level 2].
  • In patients with diabetes and NSTE ACS and multivessel disease, coronary artery bypass grafting (CABG) with the use of internal mammary artery may provide benefit over percutaneous coronary intervention (PCI) when revascularization is indicated.
    • However, PCI (with drug-eluting stents whenever possible) is acceptable for patients with less extensive disease (i.e. single-vessel disease).
  • For patients with ST-elevation ACS, immediate reperfusion strategies with either fibrinolysis or primary PCI result in similar benefits for patients with and without diabetes. The benefits of primary PCI over fibrinolysis in patients with diabetes are similar to those without diabetes.
    • However, fibrinolysis should be administered when primary PCI is not available within acceptable timeframes.
  • In patients with diabetes and STE ACS, the presence of retinopathy should not be a contraindication to fibrinolysis [Grade B, Level 2].

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 26.