What is an inhibitor of platelet aggregation?

From the Guidelines

Prasugrel is the most effective inhibitor of platelet aggregation, associated with a significant 2.2% absolute reduction and a 19% relative reduction in the primary efficacy end point, a composite of the rate of death due to cardiovascular causes, nonfatal MI, or nonfatal stroke during the follow-up period, as compared to clopidogrel 1.

Mechanism of Action

Prasugrel, a thienopyridine, achieves greater inhibition of platelet aggregation than clopidogrel by blocking ADP receptors on platelets.

Clinical Evidence

The TRITON-TIMI 38 trial, which randomly assigned 13,608 patients with moderate- to high-risk ACS to receive prasugrel or clopidogrel, demonstrated the superiority of prasugrel in reducing ischemic events, including MI, urgent TVR, and stent thrombosis 1.

Key Findings

• Prasugrel decreased cardiovascular death, MI, and stroke by 138 events (NNT=46) 1.
• The rate of MI with subsequent death due to cardiovascular causes was also reduced in the prasugrel group (P<0.02) 1.
• However, prasugrel was associated with a significant increase in the rate of bleeding, notably TIMI major hemorrhage, which was observed in 2.4% of patients taking prasugrel and in 1.8% of patients taking clopidogrel 1.

Clinical Implications

Considering the benefits and risks, prasugrel is recommended as the inhibitor of platelet aggregation in patients with acute coronary syndromes or those undergoing percutaneous coronary interventions, due to its superior efficacy in reducing ischemic events, despite the increased risk of bleeding 1.

Monitoring and Precautions

Patients taking prasugrel should be monitored for bleeding complications and informed about potential drug interactions, particularly with NSAIDs and anticoagulants. They should also alert healthcare providers about their antiplatelet therapy before any surgical procedures.

From the FDA Drug Label

Prasugrel is an inhibitor of platelet activation and aggregation through the irreversible binding of its active metabolite to the P2Y12 class of ADP receptors on platelets. Clopidogrel is an inhibitor of platelet activation and aggregation through the irreversible binding of its active metabolite to the P2Y12 class of ADP receptors on platelets.

Inhibitors of platelet aggregation are medications that prevent platelets from clumping together and forming blood clots.

• Prasugrel and clopidogrel are two examples of such inhibitors, which work by irreversibly binding to the P2Y12 class of ADP receptors on platelets.
• Both prasugrel and clopidogrel are used to prevent blood clots in patients with certain heart conditions, such as acute coronary syndrome 2 3.

From the Research

Inhibitors of Platelet Aggregation

• Prasugrel is a potent inhibitor of platelet aggregation, providing rapid and effective inhibition 4, 5, 6, 7
• It is indicated for the prevention of atherothrombotic events in patients with acute coronary syndromes undergoing percutaneous coronary intervention 4
• Prasugrel has been shown to be superior to clopidogrel in preventing ischemic events, but is associated with a higher risk of bleeding 4, 5, 7
• The efficacy of prasugrel is offset by a higher risk of bleeding, particularly in patients aged ≥75 years, those weighing <60 kg, and those with a history of stroke or transient ischemic attack 4

Comparison with Clopidogrel

• Prasugrel provides greater and more consistent platelet inhibition than clopidogrel due to earlier and more extensive formation of its active metabolite 7
• The TRITON-TIMI 38 trial showed that prasugrel led to a reduction in major adverse cardiovascular events in patients with moderate to high risk ACS scheduled for PCI, but with a significant increase in the risk of bleeding 5, 7
• A retrospective, observational, pilot study found that prasugrel is at least as effective and safe as clopidogrel in patients with ACS undergoing early invasive management 6

Mechanism of Action

• Antiplatelet agents, such as prasugrel and clopidogrel, work by inhibiting platelet activation and aggregation, which are important pathophysiologic elements of non-ST-elevation acute coronary syndromes and the ischemic complications of percutaneous coronary intervention 8
• Prasugrel inhibits platelet aggregation via P2Y(12) receptor inhibition, which is essential for the prevention of periprocedural ischemic events and long-term follow-up 5