Recommendation 21. For patients receiving ticagrelor who are experiencing significant side effects (excluding bleeding) or who are unable to tolerate the drug (and where prasugrel is not an option), we suggest de-escalating to clopidogrel with a loading dose of 600 mg followed by 75 mg daily, to be initiated at the time of the next scheduled ticagrelor dose (Weak Recommendation; Very Low-Quality Evidence).

Practical tip. The loading dose of 600 mg conveys a short-term (48 hours) pharmacodynamic advantage after the switch to clopidogrel that might be relevant in the early post-ACS/PCI period. In patients who are stable, a loading dose of 300 mg or switching directly to 75 mg daily with no loading dose are also reasonable options, especially for patients believed to be at high risk for bleeding. Timing of Platelet Inhibition after Acute Coronary Syndrome (TOPIC) study, switching from ticagrelor directly to clopidogrel 75 mg daily 1 month after ACS79 was reported to decrease bleeding without an increase in ischemic events, with the caveat that the study was not powered for ischemic outcomes.

Practical tip. The optimal time for the initiation of clopidogrel has not been extensively studied. In OPTI-CROSS, the switch was made at the next scheduled ticagrelor dose; extending to the following morning (ie, 24 hours after the last ticagrelor dose) might also be reasonable on the basis of pharmacodynamics data from the Response to Ticagrelor in Clopidogrel Nonresponders and Responders and Effect of Switching Therapies (RESPOND) study.