What is the role of anti-platelet therapy in the prevention of coronary artery disease (CAD) in patients with risk factors such as hypertension, diabetes, hyperlipidemia, and a family history of CAD?

Role of Anti-Platelet Therapy in Coronary Artery Disease Prevention

Anti-platelet therapy is essential for preventing cardiovascular events in patients with established coronary artery disease (CAD), but its role in primary prevention for patients with only risk factors (hypertension, diabetes, hyperlipidemia, family history) is limited and not routinely recommended due to bleeding risks that offset ischemic benefits. 1

Primary Prevention (Patients WITHOUT Established CAD)

Aspirin in Primary Prevention

• In patients with diabetes mellitus and cardiovascular risk factors but no established CAD, aspirin for primary prevention is NOT routinely advocated because the increased risk of major bleeding largely offsets any ischemic benefit 1
• For patients aged >65 years with multiple risk factors (hypertension, hypercholesterolemia, diabetes, obesity, or family history of premature MI), aspirin may reduce cardiovascular deaths and total cardiovascular events, but this must be weighed against bleeding risk 2
• The decision threshold is a 10-year Framingham risk score of ≥10%, where more aggressive risk factor management including consideration of aspirin becomes reasonable 3

Key Caveat for Primary Prevention

The evidence does not support routine antiplatelet therapy in patients who only have risk factors without established atherosclerotic disease. Focus should remain on aggressive management of hypertension (target <130/80 mmHg), lipid control (total cholesterol <5.0 mmol/L, LDL <3.0 mmol/L), glycemic control, and lifestyle modifications 3

Secondary Prevention (Patients WITH Established CAD)

Aspirin as Foundation

• All patients with established CAD (prior MI, angina, or documented coronary disease) should receive aspirin 75-325 mg daily indefinitely unless contraindicated 3
• Aspirin reduces the combined risk of cardiovascular death, non-fatal MI, and non-fatal stroke by approximately 25% in high-risk patients 2
• The mechanism extends beyond platelet inhibition to include suppression of vascular inflammation and increased atherosclerotic plaque stability 2

P2Y12 Inhibitors in Stable CAD

• For patients with stable CAD on long-term therapy, single antiplatelet therapy (SAPT) with either aspirin or clopidogrel 75 mg daily is appropriate 4
• Clopidogrel demonstrated superiority over aspirin in the CAPRIE study for reducing ischemic stroke, MI, or vascular death in patients with atherosclerotic vascular disease 2
• In patients with aspirin allergy, bleeding tendency, or gastrointestinal contraindications, clopidogrel serves as a reasonable alternative 3

Dual Antiplatelet Therapy (DAPT) After Acute Coronary Syndrome

Following ACS, patients require intensive antiplatelet therapy with aspirin plus a P2Y12 inhibitor:

Immediate Management

• Aspirin 162-325 mg (chewed) should be administered immediately upon presentation 5
• Add a P2Y12 inhibitor with loading dose: ticagrelor 180 mg (preferred in high-risk patients) or clopidogrel 300-600 mg 5
• For patients undergoing PCI, prasugrel 60 mg loading dose followed by 10 mg daily is indicated, though it carries higher bleeding risk and is contraindicated in patients with prior stroke/TIA 6

Duration of DAPT

• After coronary stent implantation, continue DAPT for 6-12 months, then transition to lifelong single antiplatelet therapy 3, 4
• The DAPT trial demonstrated that 30 months of DAPT was superior to 12 months in reducing MI and stent thrombosis after DES implantation, with greater benefit in ACS patients, though bleeding increased 3
• In patients at high bleeding risk, DAPT duration should be shortened to 3 months 4

Special Populations Requiring Intensified Therapy

Diabetes Mellitus

• Patients with diabetes and established CAD achieve enhanced absolute benefit from more potent antithrombotic approaches compared to those without diabetes 1
• In very high-risk diabetic patients with severe progressive CVD, consider adding clopidogrel to aspirin for dual antiplatelet therapy 3
• The net clinical benefit favors intensified long-term antithrombotic therapy in diabetic patients with CAD when excluding those at high bleeding risk 1

Lower Extremity Artery Disease (LEAD)

• Patients with both LEAD and CAD have heightened ischemic risk beyond either condition alone 3
• In the PEGASUS trial, patients with prior MI and LEAD had 60% increased risk of major adverse cardiovascular events (MACE), translating to an absolute risk reduction of 5.2% at 3 years with ticagrelor 60 mg twice daily versus placebo 3
• Prolonged DAPT in LEAD patients reduced the primary efficacy endpoint significantly (16.1% vs 27.3%; HR 0.54) compared to shorter duration 3

Complex PCI

• Patients undergoing complex PCI (≥3 stents, ≥3 lesions treated, bifurcation with two stents, total stent length >60 mm, or chronic total occlusion) benefit from prolonged DAPT duration 3

Critical Pitfalls to Avoid

Premature Discontinuation

• Discontinuing antiplatelet therapy, particularly in the first few weeks after ACS, dramatically increases the risk of subsequent cardiovascular events 6
• If bleeding occurs, manage without discontinuing antiplatelet therapy whenever possible 6
• For patients requiring CABG, discontinue prasugrel at least 7 days prior to surgery when possible 6

Bleeding Risk Factors

• Key bleeding risk factors include: age ≥75 years, body weight <60 kg, prior stroke/TIA, active bleeding, concomitant anticoagulation, chronic NSAID use, and renal insufficiency 6
• In patients <60 kg on prasugrel, reduce maintenance dose to 5 mg daily 6
• Use the PRECISE-DAPT score to assess bleeding risk and guide DAPT duration decisions 4

Drug Selection Errors

• Prasugrel is contraindicated in patients with prior stroke or TIA due to increased intracranial hemorrhage risk (4.2% thrombotic stroke + 2.3% ICH versus 1.2% with clopidogrel) 6
• In patients ≥75 years, prasugrel is generally not recommended except in high-risk situations (diabetes or prior MI) 6
• Avoid prasugrel or ticagrelor as first-line in stable CAD patients with high bleeding risk; use clopidogrel instead 4

Timing of Pretreatment

• The debate on pretreatment with P2Y12 inhibitors before coronary anatomy is defined remains controversial 3
• In NSTEMI patients, no clear benefit was observed when prasugrel loading dose was given prior to diagnostic angiography compared to at time of PCI, but bleeding risk increased with early administration 6
• Balance the need for early platelet inhibition against the risk of unnecessary bleeding if CABG is required 3

Comprehensive Management Framework

Anti-platelet therapy must be integrated within a comprehensive cardiovascular risk reduction strategy that includes:

• Blood pressure control (target <130/80 mmHg in high-risk patients) 3
• Lipid management with statins 3
• ACE inhibitors in patients with diabetes or other cardiovascular risk factors 3
• Beta-blockers after MI 3
• Glycemic control in diabetic patients 3
• Lifestyle modifications: smoking cessation, weight loss, regular exercise, dietary sodium restriction 3