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Switch from ticagrelor to clopidogrel increases platelet reactivity
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A de-escalation that consisted of a switch from ticagrelor to clopidogrel therapy conferred an increase in platelet reactivity, researchers reported in Circulation.
For the SWAP-4 randomized, open-label study, researchers assigned patients with CAD on background aspirin therapy to a 7-day run-in (180-mg loading dose followed by 90 mg twice daily) with ticagrelor (Brilinta, AstraZeneca) followed by one of four regimens: a clopidogrel 600-mg loading dose 24 hours after the last maintenance dose of ticagrelor (group A); a clopidogrel 600-mg loading dose 12 hours after the last maintenance dose of ticagrelor (group B); clopidogrel 75 mg per day maintenance dose 24 hours after the last maintenance dose of ticagrelor (group C); or a maintenance dose of ticagrelor 90 mg twice daily (group D).
Pharmacodynamic assessments were performed at baseline, during run-in, and at 2, 24, 48 and 72 hours, and at 10 days.
In all assays at all time points, ticagrelor 90 mg twice daily conferred lower platelet reactivity than any clopidogrel regimen, Francesco Franchi, MD, from the University of Florida College of Medicine – Jacksonville, and colleagues wrote.
P2Y12 reaction unit levels did not differ between group A and group C (P = .29). P2Y12 reaction unit levels were lower in group B vs. group C (P = .024).
Compared with group C, minimal platelet aggregation was lower over time in group A (P = .041) and group B (P = .028), Franchi and colleagues wrote.
Group A and group B had no differences in any pharmacodynamic test.
In group C, platelet reactivity increased at 24 hours and became statistically significant at 48 hours, sustaining out to 10 days, according to the researchers.
When a loading dose was administered, regardless of timing, the increases in platelet reactivity were diminished, they wrote.
“De-escalation from ticagrelor to clopidogrel therapy is associated with an increase of platelet reactivity suggestive of a [drug-drug interaction],” Franchi and colleagues wrote. “Administration of [a loading dose] before the initiation of [a maintenance-dose] regimen of clopidogrel mitigates these observations by delaying and hampering the increase in platelet reactivity.” – by Erik Swain
Disclosures: The study was funded in part by an investigator-initiated grant from Sanofi. Franchi reports no relevant financial disclosures. Please see the study for all other authors’ relevant financial disclosures.
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