Acetylsalicylic acid × Clopidogrel

Additive antiplatelet effect via different targets: aspirin irreversibly blocks platelet cyclooxygenase; clopidogrel inhibits the P2Y12 receptor. The combination causes more bleeding than aspirin alone: in the CURE trial, major bleeding occurred in 3.7% of patients on clopidogrel plus aspirin and in 2.7% on placebo plus aspirin (FDA Plavix label, Table 1).

Gum bleeding, epistaxis, bruising without trauma. Severe cases: GI bleeding.

Dual antiplatelet therapy (DAPT) with aspirin and clopidogrel is given after an acute coronary syndrome (ACS) and after coronary stenting. After ACS the default duration is 12 months unless bleeding risk is high. If the patient has been event-free for 3–6 months and is not at high ischaemic risk, switching to a single antiplatelet agent should be considered; at high bleeding risk this may be considered after 1 month (ESC 2023). After elective stenting for chronic coronary syndrome the default is up to 6 months, or 1–3 months at high bleeding risk (ESC 2024). Aspirin 75–100 mg/day; the clopidogrel label advises against aspirin doses above 100 mg. A proton pump inhibitor (PPI) is recommended when the risk of gastrointestinal bleeding is increased. With clopidogrel, use pantoprazole: the label advises against omeprazole and esomeprazole because they reduce formation of clopidogrel's active metabolite.