Chapter 41: Antiplatelet and Anticoagulant Therapy in Acute Coronary Syndromes
A 45-year-old man undergoes coronary stent implantation for stable ischemic heart disease. He is prescribed clopidogrel and aspirin. Which of the following is true about his antithrombotic regimen?
A. The dose of aspirin should be between 75 and 100 mg per day
B. Higher doses of aspirin could be more effective at preventing ischemic events, but at the expense of a higher risk of bleeding
C. Clinical trials support a higher dose (ie, 300 to 325 mg daily) of aspirin in patients with ischemic heart disease
D. When used with newer-generation oral P2Y12 receptor inhibitors (prasugrel and ticagrelor), no preference to aspirin dosing is given
The answer is A. (Hurst’s The Heart, 14th Edition, Chap. 41) While some pharmacodynamic studies have suggested high-dose aspirin (eg, 325 mg) may be associated with enhanced antithrombotic effects as a result of COX-1–independent mechanisms, these pharmacodynamic observations do not appear to translate into improved clinical outcomes, and when given in combination with clopidogrel, the maintenance dose of aspirin should generally be lowered to 75 to 100 mg. This is based on a post hoc analysis of data from the CURE1 (Clopidogrel in Unstable Angina to Prevent Recurrent Events) study in which similar efficacy but less major bleeding was seen in the low-dose (< 100 mg) aspirin group (option B is incorrect). Furthermore, a large-scale prospective randomized study to compare high- versus low-dose aspirin, the CURRENT/OASIS-7 (Clopidogrel Optimal Loading Dose Usage to Reduce Recurrent Events—Organization to Assess Strategies in Ischemic Syndromes)2 trial did not show a benefit to higher dose (300 to 325 mg) versus lower dose (75 to 100 mg) daily aspirin (option C is incorrect). Finally, the introduction into clinical practice of newer-generation oral P2Y12 receptor inhibitors (prasugrel and ticagrelor) that are characterized by greater potency than clopidogrel and are used in combination with aspirin has also led to questions about the optimal dose of aspirin in these patients. Although aspirin dosing did not affect the safety and efficacy profile of patients treated with prasugrel in the TRITON (Trial to Assess Improvement in Therapeutic Outcomes by Optimizing Platelet Inhibition with Prasugrel) study, a higher dose of aspirin (≥ 300 mg) was associated with reduced efficacy, albeit with no differences in bleeding, in patients treated with ticagrelor in the PLATO (Platelet Inhibition and Outcomes) trial3 (option D is incorrect).
All of the following are actions of thromboxane A2 (TXA2) except:
A. Induces platelet aggregation
B. Potent vasoconstrictor
C. Regulation of renal blood flow
D. Induces proliferation of vascular smooth-muscle cells