Cardiovascular Critical Care I

Evaluation of antiplatelet therapy can be performed with platelet function testing and/or genotyping.

However, neither is currently recommended routinely in the clinical setting. Clinical outcomes

with the use of platelet function testing to modify antiplatelet therapy (ie, high-dose vs standard-

dose clopidogrel) in patients undergoing PCI with high on-treatment platelet reactivity have been

antiplatelet therapy (CYP2C19) from large cohorts of patients undergoing PCI have shown lower

rates of major adverse cardiovascular events and lower rates of bleeding (JACC Cardiovasc Interv.

2018;11(2):181-191; J Am Coll Cardiol. 2018;71(17):1869-1877; N Engl J Med. 2019;381(17):1621-

1631).

patients with ACS. Ticagrelor showed a significant reduction in cardiovascular death, MI, and

stroke without increasing the risk of major bleeding compared with clopidogrel (N Engl J Med.

2009;361(11):1045-1057).

Trial to Assess Improvement in Therapeutic Outcomes by Optimizing Platelet Inhibition with

Prasugrel–Thrombolysis in Myocardial Infarction (TRITON-TIMI 38) trial: Evaluated prasugrel

compared with clopidogrel in patients with ACS undergoing PCI. Prasugrel was superior in

reducing ischemic events but had a higher risk of major bleeding, particularly in patients with a

history of stroke or TIA (N Engl J Med. 2007;357:2001-2015).

Intracoronary Stenting and Antithrombotic Regimen: Rapid Early Action for Coronary Treatment

(ISAR-REACT) 5 trial: Compared prasugrel and ticagrelor in patients with ACS treated invasively.

Prasugrel was more effective in reducing the composite of death, MI, or stroke, with a bleeding risk

similar to ticagrelor (N Engl J Med. 2019;381(16):1524-1534).

The response to antiplatelets that require hepatic biotransformation for activation (clopidogrel and

prasugrel) can be altered in patients with liver dysfunction, patients with cardiogenic shock, or

those undergoing therapeutic hypothermia because of the delay in gut absorption and isoenzyme

activity. In other situations, such as when enteral administration is not an option, parenteral

antiplatelets may be considered (Table 5). These options include glycoprotein IIb/IIIa inhibitors

and cangrelor, which have been studied primarily in the setting of PCI but have data supporting

their use as bridging agents.

Cardiol 2011;58:e123-210; J Am Coll Cardiol 2011;58:e44-122; Br J Clin Pharmacol 2011;72:647-57)

Medication

Aspirin

Clopidogrel

Prasugrel

Ticagrelor

Mechanism

of action

Inhibits

thromboxane

A2–mediated

platelet

activation

Inhibits ADP-

mediated platelet

activation at

P2Y12 receptor

Inhibits ADP-

mediated platelet

activation at

P2Y12 receptor

Inhibits ADP-mediated

platelet activation at

P2Y12 receptor

Loading dose

162–325 mg

300 mg for medical

management

600 mg for invasive

management

60 mg

180 mg

Maintenance dose

81 mg daily

75 mg daily

5–10 mg dailya

90 mg BID

Route

Oral

Oral

Oral

Oral

Prodrug

No

Yes

Yes

No

Reversible platelet

binding

No

No

No

Yes