Expert consensus offers guidance on switching platelet P2Y12 receptor-inhibiting therapies
A recent expert consensus statement offered recommendations on switching between oral P2Y12 inhibitors and between IV and oral P2Y12 inhibitors.
Because practice guidelines have offered limited advice in these areas, experts from North America and Europe with expertise in the field of antiplatelet therapy were invited to develop a consensus statement to help provide clinicians with practical guidance. The statement noted that the decision to switch therapies can be affected by many factors, including clinical setting, patient characteristics, costs, side effects, and patient or physician preference. The expert recommendations included the following.
When escalating therapy with oral P2Y12 inhibitors, that is, switching from clopidogrel to prasugrel or ticagrelor, the consensus authors recommend using a loading dose of 60 or 180 mg, respectively, in the early phase of treatment, particularly when treatment is acute. The loading dose can be given regardless of when the last dose of clopidogrel was received, the consensus statement said, and should be followed by standard maintenance-dose regimens, which would be 10 mg/d for prasugrel and 80 mg twice daily for ticagrelor. After the early phase of treatment, the consensus statement said it would be reasonable to escalate therapy with a maintenance dose of 10 mg/d or 90 mg twice daily, respectively, without use of a loading dose. For de-escalating oral treatment, that is, switching from prasugrel or ticagrelor to clopidogrel, the group did not reach consensus for the acute or early phase of treatment, since data in this area are lacking, but outlined several possible options. The statement noted that after the early phase or in patients who are more stabilized, clinicians should consider using a 75-mg maintenance dose of clopidogrel without a loading dose when the next dose is scheduled.
When switching from ticagrelor to prasugrel, a 60-mg loading dose of prasugrel should always be used regardless of early or late timing due to data suggesting the potential for a drug-drug interaction. Switching with a 10-mg maintenance dose should be avoided, the statement said. Data do not suggest a drug-drug interaction with a switch from prasugrel to ticagrelor, so the statement noted that a standard 90-mg twice-daily maintenance dose can be used at the time of the next scheduled dose without a loading dose in this case. In patients with acute coronary syndrome who are in the acute treatment phase, however, a loading dose 24 hours after the last prasugrel dose can be considered, the statement noted.
When bridging from oral P2Y12 inhibitors to cangrelor, the statement noted that it is reasonable to wait to start cangrelor bridging for up to three to four days after prasugrel is discontinued and two to three days after clopidogrel and ticagrelor discontinuation in order to minimize the time of infusion. When transitioning from cangrelor to oral P2Y12 inhibitors, cangrelor should be started before percutaneous coronary intervention and continued for at least two hours or for the duration of the procedure, whichever period is longer, the statement said, adding that the infusion can be continued for up to four hours at the physician's discretion.
When changing from cangrelor to a thienopyridine, the latter should be given immediately after cangrelor is discontinued with a loading dose, 600 mg for clopidogrel or 60 mg for prasugrel, to avoid a potential drug-drug interaction, according to the statement. The statement noted that the FDA states that ticagrelor can be given before, during, or immediately after cangrelor infusion while the European Medical Agency states that it should be given immediately after cangrelor infusion is discontinued or up to 30 minutes before the infusion ends. The expert consensus statement noted that ticagrelor should be given as a 180-mg loading dose and recommended that earlier administration should be considered to help minimize any potential gap in platelet inhibition during transition.
The expert consensus statement, which is available free of charge online, offers additional advice on switching therapies, including a table indicating type of class switch and potential for drug-drug interactions and figures summarizing all of the consensus recommendations. The statement also discusses situations that require special consideration, such as patients undergoing cardiac and noncardiac surgery, patients with bleeding or those at high risk for bleeding complications, and patients who require oral anticoagulation. It was published online Oct. 30 by Circulation and appeared in the Nov. 14, 2017, issue.