Switching to cangrelor in CAD patients pretreated with ticagrelor safe without concerns for drug interactions: SWAP-5 Study
USA: The use of cangrelor in stable coronary artery disease (CAD) patients pretreated with ticagrelor results in enhanced platelet inhibition and the absence of drug-drug interaction (DDI) compared to placebo, according to findings from the small SWAP-5 trial. The lack of DDI was indicated by no differences in pharmacokinetic (PK) and pharmacodynamic (PD) profiles after discontinuation of drug infusion.
The findings from the SWAP-5 trial were produced in the JACC: Cardiovascular Interventions.
Considering that no studies have been designed to rule out a drug-drug interaction when cangrelor is used in patients pretreated with ticagrelor, Francesco Franchi, University of Florida College of Medicine-Jacksonville, Jacksonville, FL, USA, and colleagues aimed to rule out a DDI among patients treated with cangrelor who have been pretreated with ticagrelor.
For this purpose, the researchers performed a randomized, prospective, cross-over, placebo-controlled, double-blind, pharmacodynamic and pharmacokinetic study. In the study, 20 patients with CAD were pretreated with a 180-mg ticagrelor loading dose (LD) and, after 1 hour, randomized to placebo or cangrelor (bolus and infusion for 2 hours).
After 1-4 weeks of washout, patients were crossed over-PK analysis comprised of ticagrelor plasma levels and its active metabolite. PD assessments included light transmittance aggregometry, VerifyNow P2Y12 reaction units (PRU), Total Thrombus-Formation Analysis System, and vasodilator-stimulated phosphoprotein. Assessments of PK/PD were done at 7-time points.
The study led to the following findings:
- Cangrelor addition to patients pretreated with ticagrelor resulted in a significant reduction in PRU at 30 min and 1 hour after starting infusion compared to placebo.
- At 2 hours after stopping cangrelor/placebo infusion, PRU was low and similar in both groups (16.9 vs 12.6; mean difference: 4.3), meeting the non-inferiority primary endpoint (pre-defined non-inferiority margin 45 PRU).
- Consistent findings were shown with all PD assays.
- PK tracked PD findings with no differences between groups in plasma levels of ticagrelor and its metabolite.
The SWAP-6 study will look at the approach of switching between cangrelor and prasugrel in patients undergoing percutaneous coronary intervention (PCI); results are expected to be released in 2023.
The results indicate that patients who develop an acute coronary syndrome requiring urgent PCI could safely be bridged with cangrelor after pretreatment with ticagrelor without worrying about a loss of antithrombotic protection after discontinuation.
"Our findings provide insights that if a patient has been pretreated for a short time, cangrelor does provide additional platelet inhibition and can be used safely without concerns for drug interactions," the researchers wrote.
Reference:
Franchi F, Ortega-Paz L, Rollini F, Galli M, Been L, Ghanem G, Shalhoub A, Ossi T, Rivas A, Zhou X, Pineda AM, Suryadevara S, Soffer D, Zenni MM, Angiolillo DJ. Cangrelor in Patients with Coronary Artery Disease Pre-treated with Ticagrelor: The Switching Antiplatelet (SWAP)-5 Study. JACC Cardiovasc Interv. 2022 Oct 21:S1936-8798(22)02005-2. doi: 10.1016/j.jcin.2022.10.034. Epub ahead of print. PMID: 36317958.
