No – Dual Antiplatelet Therapy is NOT Indicated
For patients with chronic atherosclerotic vessel disease and microvascular ischemic changes who have no recent acute coronary syndrome, percutaneous coronary intervention, or ischemic stroke/TIA, dual antiplatelet therapy is not recommended; single antiplatelet therapy is the appropriate treatment. 1
Evidence-Based Rationale
The Guideline Position is Clear
In patients with symptomatic peripheral artery disease (PAD) without recent revascularization, the benefit of dual antiplatelet therapy is uncertain (Class 2b, Level B-R recommendation). 1 This represents the highest quality guideline evidence directly addressing your question, as chronic atherosclerotic vessel disease without acute events falls into this category.
The 2024 ACC/AHA/AACVPR guidelines explicitly state that "no evidence is available to support the use of more potent antiplatelet agents or dual antiplatelet therapy outside of a recent revascularization procedure" in patients with symptomatic PAD. 1
The use of dual antiplatelet therapy in stable atherosclerotic disease is associated with higher risks of bleeding that may offset any lowering of the risk of ischemic events. 1
What IS Recommended Instead
Single antiplatelet therapy with clopidogrel alone (75 mg daily) is recommended to reduce the risk of major adverse cardiovascular events (MACE) in patients with symptomatic PAD (Class 1, Level B-R). 1
Single antiplatelet therapy with aspirin alone (75-325 mg daily) is also recommended to reduce the risk of MACE (Class 1, Level C-LD). 1
Clopidogrel has demonstrated improved efficacy compared with aspirin for prevention of MACE in the CAPRIE trial, with similar rates of bleeding. 1
The Evidence Against Dual Therapy in Stable Disease
Studies examining dual antiplatelet therapy outside the setting of recent revascularization have been conducted primarily in subgroups of patients with PAD enrolled in larger trials (PEGASUS-TIMI 54 and CHARISMA), and these subgroups were underpowered to fully examine efficacy and safety. 1
The CHARISMA trial specifically tested dual antiplatelet therapy in patients with stable atherosclerotic disease and found uncertain benefit with increased bleeding risk. 1
Research confirms that dual antiplatelet therapy carries an increased risk of bleeding, and patients with chronic cerebrovascular disease (microvascular ischemic changes) are at particularly high risk for intracranial hemorrhage. 2
When Dual Therapy WOULD Be Indicated
The guidelines are very specific about when dual antiplatelet therapy is appropriate:
Within 1-6 months after endovascular revascularization for PAD (Class 2a, Level C-LD). 1
For 12 months after acute coronary syndrome (Class 1, Level A). 1
For 21-30 days after high-risk TIA or minor ischemic stroke. 3
After recent percutaneous coronary intervention with stent placement. 1
None of these acute scenarios apply to your patient with chronic, stable atherosclerotic disease.
Alternative Consideration: Rivaroxaban Plus Aspirin
Low-dose rivaroxaban (2.5 mg twice daily) combined with low-dose aspirin is effective to reduce the risk of MACE and major adverse limb events in patients with symptomatic PAD (Class 1, Level A). 1
This combination prevents ischemic events compared with aspirin alone but carries a higher risk of major bleeding. 1
This represents an alternative to dual antiplatelet therapy, not a reason to use dual antiplatelet therapy.
Critical Pitfalls to Avoid
Do not extrapolate acute coronary syndrome or post-PCI guidelines to patients with chronic stable atherosclerotic disease. The pathophysiology and thrombotic risk profiles are fundamentally different. 1
Do not assume that "more is better" with antiplatelet therapy in stable disease. The bleeding risk increases substantially without proportional ischemic benefit. 1, 2
Do not confuse microvascular ischemic changes (chronic small vessel disease) with acute ischemic stroke or TIA. These are distinct clinical entities with different treatment algorithms. 1, 2