Dual Antiplatelet Therapy: Unlocking the Future of Cardiovascular Disease Management

Abstract

Dual Antiplatelet Therapy (DAPT) is a cornerstone in managing thrombotic cardiovascular conditions, particularly in patients undergoing percutaneous coronary intervention (PCI), those with acute coronary syndrome (ACS), and individuals at risk of cerebrovascular and peripheral arterial events. This review explores the mechanisms of various antiplatelet agents, their clinical indications, and the optimal duration of DAPT across different patient populations. While DAPT effectively reduces ischemic complications, prolonged therapy is associated with an increased risk of bleeding, necessitating a tailored approach based on individual risk assessments. Recent advancements, including novel antiplatelet agents and evolving guidelines, emphasize balancing ischemic protection with bleeding risk. This review provides an in-depth analysis of the latest clinical evidence, emerging therapies, and guideline recommendations for optimizing DAPT in various cardiovascular conditions.

Introduction

Cardiovascular diseases are a leading cause of death globally, with thrombotic events being key in disease progression. Dual antiplatelet therapy (DAPT) has significantly improved outcomes in conditions like acute coronary syndrome (ACS), ischemic stroke, and peripheral artery disease (PAD) by reducing recurrent thrombotic events. Treatment selection and duration depend on patient-specific factors and the balance between ischemic risk and bleeding.

Mechanism of Antiplatelet Agents:

1. Aspirin (COX inhibitor): Irreversibly inhibits COX-1, reducing thromboxane A2 and preventing platelet aggregation.

2. Thienopyridines (clopidogrel, prasugrel, ticagrelor): Block the P2Y12 receptor; prasugrel is the most potent.

3. Glycoprotein IIb/IIIa inhibitors (e.g., abciximab): IV agents used in ACS.

4. PAR-1 antagonists (vorapaxar): Inhibit thrombin-induced platelet activation.

5. PDE inhibitors (dipyridamole, cilostazol): Increase cAMP in platelets, reducing aggregation and causing vasodilation.

Clinical Indications for DAPT:

• ACS (STEMI, NSTEMI, UA): Reduces major adverse cardiovascular events.

• Post-PCI: 6–12 months for drug-eluting stents, 1 month for bare-metal stents.

• CABG: Recommended for 1 year post-ACS.

• Ischemic Stroke/TIA: Short-term DAPT (21–30 days).

• PAD: Improves walking distance and reduces limb-related events.

• Stent Thrombosis Prevention: Essential after PCI.

Duration of DAPT:

1. ACS:

   • Standard: 12 months.

   • Short-term (3–6 months): Considered for high bleeding risk patients.

   • Studies (e.g., CURE, REDUCE, SMART-CHOICE) support shorter duration in selected patients.

2. Stable CAD:

   • Long-term DAPT not routinely beneficial (CHARISMA, THEMIS trials).

   • THEMIS-PCI showed benefit in patients with prior PCI.

   • Rivaroxaban + ASA (COMPASS) lowered events but increased bleeding.

3. Post-PCI with AF:

   • Triple therapy (aspirin + clopidogrel + anticoagulant) for 1 month.

   • De-escalation to P2Y12 + OAC preferred beyond 1 month to reduce bleeding.

4. CABG:

   • ASA started within 6 hours post-op and continued indefinitely.

   • DAPT (ASA + clopidogrel/ticagrelor) may improve graft patency.

5. TAVI:

   • ASA or clopidogrel monotherapy is safer.

   • DAPT increases bleeding without added benefit.

6. PAD:

   • Monotherapy offers limited benefit in asymptomatic PAD.

   • DAPT or vorapaxar may reduce limb ischemic events but increase bleeding.

   • Cilostazol improves claudication symptoms and reduces revascularization rates.

Conclusion

DAPT remains a cornerstone in preventing thrombotic complications in patients with cardiovascular diseases, yet its use requires careful consideration of both ischemic and bleeding risks. While standard therapy durations have been established for conditions such as ACS, PCI, and stroke, recent studies suggest that individualized approaches, guided by patient-specific risk factors, may enhance treatment outcomes. The emergence of novel antiplatelet agents and evolving guideline recommendations highlight the need for continuous re-evaluation of DAPT strategies. Future research should focus on refining risk stratification models and exploring alternative therapies to optimize cardiovascular protection while minimizing adverse events. A patient-centered approach, integrating clinical judgment with the latest evidence, is essential for achieving the best outcomes in antiplatelet therapy.

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