Help for Clinicians Whose Patients Need to Switch P2Y12 Inhibitors

DENVER, CO—With several P2Y12 inhibitors available, clinicians are increasingly faced with choices about whether to switch their patients with ACS or a recent stent implantation from one to another, but there hasn’t been much guidance on how to do that. Now, a group of international experts has filled that void by releasing a consensus document to ease decision-making.

“There are very limited data on how and when to switch, and accordingly, practice guidelines provide very limited insights to the clinician on what to do,” Dominick Angiolillo, MD, PhD (University of Florida College of Medicine-Jacksonville), one of the co-chairs of the group, told TCTMD.

So he and co-chair Matthew Price, MD (Scripps Clinic, La Jolla, CA), pulled together antiplatelet experts from North America and Europe to aggregate available data and provide practical advice on how to switch between P2Y12 inhibitors, which include oral agents—clopidogrel, prasugrel (Effient; Eli Lilly), and ticagrelor (Brilinta; AstraZeneca)—and IV cangrelor (Kengreal; Chiesi USA).

The result of the collaboration is a consensus document published October 30, 2017, ahead of print in Circulation to coincide with presentations by Angiolillo and Price at TCT 2017 in Denver, CO.

Registries have shown that up to 50% of patients swap P2Y12 inhibitors, Angiolillo noted. In their paper, the authors say “a variety of factors may contribute to the decision to switch, including the clinical setting, patient characteristics, concomitant therapies, costs, social issues, development of side effects, medication adherence, and patient/physician preference.”

When making a switch, there is the potential for drug-drug interactions that can either enhance or dampen platelet inhibition, leading to greater risks of bleeding or thrombotic events, respectively. Although there are few large-scale clinical studies that address the best approaches for switching between P2Y12 inhibitors, data from pharmacodynamic and registry studies can be used to help inform the issue.

For the consensus document, Angiolillo et al start with an overview of the pharmacology of the available agents, leaving out ticlopidine, which is no longer widely used.

They then move into a discussion about the different switching modalities, including escalation from clopidogrel to more intense therapy, de-escalation from prasugrel or ticagrelor to clopidogrel, a change between ticagrelor and prasugrel, or a transition between oral agents and cangrelor. The document includes a table to help clinicians sort out which types of switches have the potential for a drug-drug interaction.

After reviewing the literature, the authors make recommendations on switching P2Y12 inhibitors, taking into consideration the pharmacological profiles of the drugs; data from trials, registries, and pharmacodynamic studies; and the potential for thrombotic complications based on the amount of time passed since the event that led to treatment. The recommendations are deemed mostly consensus-based because of the limited safety and efficacy data in this area, Angiolillo et al say.

Angiolillo pointed to two figures in the paper as the most important because they provide visual summaries of the recommendations. One covers the switch between oral P2Y12 inhibitors in the acute/early phase (within 30 days of the index event) or the late/very late phase (beyond 30 days), providing recommended timing and dosing. The other describes bridging from oral agents to IV cangrelor and transitioning from cangrelor to oral therapy.

“Our consensus document aims to provide some guidance, with the understanding that there could be variations in clinical practice,” Angiolillo said. “A lot may depend on personal experience or preference of the individual physician and a lot may depend on the patient that you have in front of you.”

Eric Bates, MD (University of Michigan, Ann Arbor), called the consensus document “the most definitive statement to date on switching and bridging.” There haven’t been good guidelines on how to do this, he added, and Angiolillo et al “give a very clear pharmacological approach on how to maintain platelet inhibition.”

Bates noted that there is increasing interest in de-escalation, in particular, with doctors thinking more about the bleeding risk accompanying more intense therapy and worrying about the higher price of ticagrelor and prasugrel when treating patients who don’t have good insurance coverage. The latter issue could be particularly important at hospital discharge, at least in the United States, he said, because there is a concern with sending a patient home with a prescription that they’ll be unlikely to fill due to cost.

Also, recent trials, including TROPICAL-ACS, have started to provide some evidence that de-escalating therapy after hospital discharge following an initial period of high ischemic risk could be a feasible option, he said.

Within that context, the new consensus document is a useful addition, Bates said.

“This is a pretty sound, pharmacologically-oriented roadmap on how to switch without decreasing platelet inhibition,” he said. “It’s a really nice, clarifying piece of work to summarize a controversial subject that hasn’t been covered well before by research or by clinical guidelines.”

Angiolillo said that there are ongoing studies that will help inform the switching issue in the future. “We’ll be learning a lot more about the topic in the years to come, and I believe that this document sets the foundation to develop upon,” he commented.