1. Overview & Pathophysiology
Cardiovascular disease (CVD) is the primary cause of death for people with diabetes.
- Vascular Age: Diabetes significantly accelerates vascular aging. Having diabetes confers a CVD risk equivalent to aging approximately 15 years.
- Proximate vs. Lifetime Risk: While young people with diabetes may have low proximate (<10 years) risk, their lifetime risk is extremely high. Therefore, early intervention is justified.
The “Vascular Protection” Concept: Multifactorial intervention (treating lipids, BP, glucose, and lifestyle simultaneously) provides benefit greater than the sum of its parts.
Key Study: The STENO-2 Trial showed that intensive multifactorial intervention reduced major adverse cardiac events (MACE) by 53% and mortality by 20%.
2. Patient Education: The ABCDEs
The guidelines recommend teaching patients the “ABCDEs” to reduce heart attack and stroke risk :
A = A1C (Target usually ).
B = BP (Target mmHg).
C = Cholesterol (LDL-C mmol/L).
D = Drugs to protect the heart (ACEi/ARBs, Statins, and specific glucose-lowering agents like SGLT2i/GLP-1 RA).
E = Exercise / Eating (Healthy behaviors).
S = Stop Smoking (and manage Stress)
3. Pharmacotherapy for CV Protection
This section focuses on the “D” (Drugs) of the ABCDEs.
A. Lipid-Modifying Therapies (Statins)
Statins are recommended based on risk categories, not just LDL levels.
- Who needs a Statin?
- Clinical CVD: Anyone with established cardiovascular disease.
- Age 40 years: All individuals with Type 2 diabetes.
- Age < 40 years: Only if “High Risk,” defined as:
- Diabetes duration years (and age ).
- Microvascular complications present.
- Warrants therapy based on other risk factors (e.g., Familial Hypercholesterolemia).
- Second-Line: If LDL goals are not met, Ezetimibe or PCSK-9 inhibitors (Evolocumab) may be added.
B. RAAS Inhibition (ACE Inhibitors / ARBs)
- Indication:
- Clinical CVD: All patients.
- Age 55 years: If they have one additional CV risk factor OR end-organ damage (albuminuria, retinopathy, LVH).
- Microvascular Complications: To delay progression (e.g., albuminuria).
- Note: The previous recommendation to treat everyone regardless of risk factors was removed in 2018. Now requires an additional risk factor or end-organ damage.
- Pregnancy: ACEi/ARBs and Statins are contraindicated in pregnancy.
C. Antiplatelet Therapy (ASA / Aspirin)
- Secondary Prevention: YES. Routine use (81–162 mg) is recommended for those with established CVD.
- Primary Prevention: NO. ASA should not be used routinely for primary prevention due to bleeding risks outweighing benefits.
- Exception: May be considered on an individual basis for those with very high risk/multiple risk factors.
- Clopidogrel: Use if ASA intolerant.
D. Antihyperglycemic Agents with CV Benefit
For patients with Type 2 diabetes and clinical CVD who are not at glycemic target, specific agents with proven CV benefit should be prioritized:
Empagliflozin (SGLT2i): Reduced CV mortality and all-cause mortality (EMPA-REG OUTCOME).
Liraglutide (GLP-1 RA): Reduced MACE (CV death, non-fatal MI, stroke) (LEADER).
Canagliflozin (SGLT2i): Reduced MACE (CANVAS), but noted increased amputation risk in trial.
(NOTE: Since the publication of the guidelines semaglutide po/sc and tirzepatide have demonstrated significant effect on MACE)
4. Glycemic Control & CV Outcomes (The Trials)
Understanding the difference between early and late intervention is key.
- Early Intervention (DCCT/UKPDS): Intensive control early in the disease course has a “legacy effect,” reducing CV events long-term.
- Late Intervention (ACCORD/ADVANCE/VADT): In older patients with long-standing diabetes and CVD risk, intensive glucose lowering (targeting A1C < 6.0-6.5%) did NOT reduce CV events and increased mortality in the ACCORD trial.
- Takeaway: Aggressive A1C targets may be dangerous in high-risk, long-standing diabetes.
5. Diabetes Canada Clinical Practice Guidelines Recommendations
Key takeaways from the “Recommendations” section (Page S169).
- Statin Therapy: Recommended for all with clinical CVD, or Type 2 diabetes Age 40, or young patients with microvascular complications/long duration [Grade A/D].
- ACEi/ARB: Recommended for clinical CVD, or Age 55 with add-on risk/organ damage, or microvascular complications [Grade A/D].
- ASA: Recommended for Secondary Prevention [Grade B]. Not recommended routinely for Primary Prevention [Grade A].
- CVD Benefit Agents: In adults with T2D and clinical CVD, add Empagliflozin [Grade A, Level 1A], Liraglutide [Grade A, Level 1A], or Canagliflozin [Grade C, Level 2] if not at target.
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