Antithrombotic Drugs

Antithrombotic therapy plays a pivotal role in the prevention and management of thrombotic events within the cardiovascular system. It encompasses a range of medications and strategies aimed at inhibiting the formation of blood clots, thereby reducing the risk of potentially serious conditions like heart attacks and strokes. From antiplatelet agents to anticoagulants, these therapies are tailored to specific clinical scenarios, ensuring optimal patient outcomes. This introduction provides a glimpse into the crucial role that antithrombotic therapy plays in safeguarding cardiovascular health.

Disease based Antiplatelet therapy:

DiseaseRecommended Anticoagulation therapy
Carotid Artery Disease- Single antiplatelet therapy (SAPT) is recommended for asymptomatic patients with carotid artery stenosis >50%.
- Lifelong low-dose aspirin is advised to reduce the risk of stroke and other cardiovascular (CV) events.
- In symptomatic extracranial carotid stenosis, antiplatelet monotherapy is recommended. Clopidogrel (75 mg/day) is an alternative for patients with aspirin intolerance.
- Dual antiplatelet therapy (DAPT) may be considered within 24 hours of a minor ischemic stroke or transient ischemic attack (TIA), and may be continued for 1 month in patients treated conservatively.
- DAPT is recommended in patients undergoing Carotid Artery Stenting (CAS). The optimal duration of DAPT following CAS is unknown. It may be prolonged beyond 1 month after CAS in the presence of recent (<12 months) Myocardial Infarction (MI) and low bleeding risk.
Lower Extremity Artery Disease (LEAD)- Antiplatelet agents are used in patients with Lower Extremity Artery Disease (LEAD) to prevent limb-related and general CV events. Specific indications for various antiplatelet strategies remain unclear.
- Lifelong low-dose aspirin is recommended for patients with Intermittent Claudication (IC) and Critical Limb Threatening Ischemia (CLTI).
- Clopidogrel may be considered in patients with IC and CLTI who are intolerant to aspirin.
- Data on the superiority of Dual Antiplatelet Therapy (DAPT) (with clopidogrel) over aspirin alone to reduce CV events in patients with LEAD are lacking.
- Vorapaxar, a protease-activated receptor-1 inhibitor, may be considered as an adjunct to standard antiplatelet therapy for secondary prevention in patients with clinical LEAD. It reduces the risk of acute limb ischemia and peripheral revascularization, but increases the risk of bleeding.
- Data regarding the use of direct oral thrombin and factor Xa inhibitors in LEAD are not yet available.
After Bypass Grafting- Aspirin improves graft patency, particularly in prosthetic grafts, compared to placebo.
- Aspirin is comparable to vitamin K antagonist (VKA) in terms of graft patency, but VKA is associated with a higher risk of major bleeding.
- Adding warfarin to aspirin does not improve graft patency, but increases the risk of major bleeding.
- Dual Antiplatelet Therapy (DAPT) with aspirin plus clopidogrel may be considered for patients with prosthetic grafts, showing potential benefits in reducing the risk of graft failure, but with an increased risk of bleeding.
After Endovascular Therapy- Dual Antiplatelet Therapy (DAPT) is recommended for at least 1 month after intervention, irrespective of stent type.
- The optimal duration of DAPT after stenting below-the-knee arteries is not specifically addressed.
- Anticoagulation after percutaneous infra-inguinal revascularization does not improve vascular patency and increases the risk of bleeding.
Concomitant CAD and LEAD- Patients with both Coronary Artery Disease (CAD) and LEAD have a worse prognosis.
- The coexistence of LEAD impacts the type and duration of antiplatelet therapy, especially in cases of prior coronary stenting or acute coronary syndrome (ACS).
- Prolonged Dual Antiplatelet Treatment (DAPT) may be considered for patients with concomitant LEAD after ACS. It reduces the risk of composite endpoints (death, MI, or cerebrovascular accidents) in this subgroup.

Important research and publications related to antiplatelet therapy

Study/TrailsResults
CHARISMA Trial- Asymptomatic CAD was an inclusion criteria in 7% of patients enrolled. - No benefit observed between Dual Antiplatelet Therapy (DAPT) vs. Single Antiplatelet Therapy (SAPT).
CARESS Study - DAPT vs. aspirin reduced silent cerebral micro-emboli by 37% after 7 days. - No life-threatening intracranial or major bleeding observed, but sample size was small.
Clopidogrel vs. Aspirin (CAPRIE) - At 3 years, clopidogrel was superior to aspirin in patients with clinical LEAD. - Significant reductions in CV mortality and MACE observed. - Similar benefit in LEAD patients with diabetes.
EUCLID Trial- Ticagrelor compared to clopidogrel showed no significant difference in MACE or major bleeding.
CASPAR Trial (Subgroup Analysis) - In patients with prosthetic grafts, DAPT reduced primary efficacy endpoint compared to aspirin alone. - No statistically significant difference when venous grafts were used. - Total bleeding was more frequent on DAPT.
Zilver PTX Trial - Mandated DAPT for 2 months after provisional drug-eluting stents vs. bare-metal stents.
IN.PACT SFA Trial - Half of the patients were on DAPT at 1 year after intervention with drug-eluting stents.
Dutch Bypass Oral Anticoagulants or Aspirin Study - No difference in graft patency between aspirin and vitamin K antagonist (VKA) over 2 years of follow-up. - Increased major bleeding risk with VKA. - Fewer venous bypass occlusions under VKA vs. aspirin.
PRODIGY Trial- Prolonged (24 months) vs. short (6 months) Dual Antiplatelet Treatment (DAPT) conveyed a lower risk of composite endpoints (death, MI, or cerebrovascular accidents) in patients with concomitant LEAD.
Antithrombotic Trialists Collaboration- Aspirin significantly reduced Major Adverse Cardiovascular Events (MACE) vs. controls in patients with Intermittent Claudication (IC).
CAPRIE Trial (Post Hoc Analysis)- At 3 years, clopidogrel was superior to aspirin in the subgroup of patients with clinical LEAD, showing significant reductions in CV mortality and MACE. - Similar benefit observed in LEAD patients with diabetes.
COMPASS Trial- The trial compared rivaroxaban monotherapy, dual therapy (aspirin plus rivaroxaban), and aspirin monotherapy in patients with CAD or LEAD.
Effects of Ticagrelor and Clopidogrel in Patients with Peripheral Artery Disease (EUCLID) Trial - Ticagrelor was compared to clopidogrel in patients with symptomatic LEAD. The trial failed to show any difference regarding MACE or major bleeding.
Clopidogrel and Acetylsalicylic Acid in Bypass Surgery for Peripheral Arterial Disease (CASPAR) Trial - In patients with below-the-knee bypass grafting, no significant difference was found between aspirin plus placebo vs. aspirin plus clopidogrel regarding primary efficacy endpoints. - Subgroup analysis showed potential benefits in patients with prosthetic grafts.
PEGASUS-TIMI 54 TrialConsider long-term ticagrelor on top of low-dose aspirin in LEAD patients with prior MI (<3 years).
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