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Switching From Cangrelor to Prasugrel: SWAP-6 Study
Quick Takes
- After stopping cangrelor infusion, in patients receiving cangrelor and prasugrel concomitantly, there was a marked increase in platelet reactivity, with levels significantly higher than those receiving prasugrel only.
- These data suggest presence of a drug-drug interaction when prasugrel is started at the time of cangrelor administration, which translates into a gap in platelet inhibition for at least 2 hours after stopping cangrelor infusion.
- Clinicians should avoid concomitant use of prasugrel and cangrelor and instead in cangrelor-treated patients, prasugrel should be administered at the end of cangrelor infusion.
Study Questions:
Is there a drug-drug interaction (DDI) when transitioning from intravenous P2Y12 inhibition with cangrelor to oral P2Y12 inhibition with prasugrel?
Methods:
The investigators conducted SWAP-6 (Switching Antiplatelet-6), a prospective, randomized, three-arm, open-label pharmacokinetic (PK) and pharmacodynamic (PD) study. Patients (n = 77) were randomized to: 1) prasugrel only at start of percutaneous coronary intervention (PCI); 2) cangrelor plus prasugrel concomitantly at start of PCI; or 3) cangrelor at start of PCI plus prasugrel at end of infusion. Cangrelor infusion was maintained for 2 hours. PK/PD assessments were performed at baseline and 6 time points post-randomization. The primary endpoint was noninferiority in VerifyNow P2Y12 reaction units (PRU) measured at 4 hours after randomization between cangrelor plus prasugrel concomitantly administered versus prasugrel only. PK assessments included plasma levels of prasugrel’s active metabolite (P-AM). An analysis of covariance method with a general linear model, with treatment as the main effect and baseline values of platelet reactivity as a covariate, was used to evaluate the primary endpoint and all between-group comparisons at each time point.
Results:
Compared with prasugrel, cangrelor further enhances P2Y12 inhibitory effects. At 4 hours post-randomization, PRU levels were significantly lower with prasugrel only compared to cangrelor and prasugrel concomitantly administered (least-squares method difference, 130; 95% confidence interval, 85-176), failing to meet the prespecified noninferiority margin. Findings were corroborated by multiple PD assays. P-AM levels were not affected by concomitant administration of cangrelor and were low at the end of cangrelor infusion.
Conclusions:
The authors report that concomitant administration of prasugrel with cangrelor in patients undergoing PCI leads to a marked increase in platelet reactivity after stopping cangrelor infusion, supporting the presence of a DDI.
Perspective:
This study reports that after stopping cangrelor infusion, in patients receiving cangrelor and prasugrel concomitantly, there was a marked increase in platelet reactivity, with levels significantly higher than those receiving prasugrel only. These data suggest presence of a DDI when prasugrel is started at the time of cangrelor administration, which translates into a gap in platelet inhibition for at least 2 hours after stopping cangrelor infusion. Overall, clinicians should avoid concomitant use of prasugrel and cangrelor and instead in cangrelor treated patients, prasugrel should be administered at the end of cangrelor infusion. Of note, the gap in platelet inhibition is less apparent, albeit still present when administering prasugrel at the end of cangrelor infusion.
Clinical Topics: Cardiovascular Care Team, Invasive Cardiovascular Angiography and Intervention, Prevention
Keywords: Drug Interactions, ESC Congress, ESC23, Myocardial Ischemia, Percutaneous Coronary Intervention, Pharmacogenomic Variants, Platelet Aggregation Inhibitors, Prasugrel Hydrochloride, Purinergic P2Y Receptor Antagonists, Secondary Prevention
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