July 16th, 2012
Ticagrelor Joins Clopidogrel and Prasugrel in Updated NSTEMI Guidelines
Ticagrelor (Brilinta, AstraZeneca) gains equal standing with prasugrel (Effient, Lilly) and clopdiogrel in the newly released focused update of the ACCF/AHA guidelines for unstable angina and non-ST-elevation myocardial infarction (NSTEMI). The change had been widely anticipated since last year’s FDA approval of ticagrelor.
“We have put it on equal footing with two other antiplatelet medications, clopidogrel and prasugrel,” said Hani Jneid, the, lead author of the update, in a press release issued by the AHA.
As part of the standard of dual-antiplatelet therapy (DAPT), aspirin should be given immediately to patients with unstable angina and NSTEMI. Aspirin use should be continued for as long as it is tolerated.
The document offers a highly detailed, near-Talmudic analysis of the literature, with a great deal of attention devoted to analysis of the TRITON-TIMI 38 trial of prasugrel and the PLATO trial of ticagrelor. Overall, the committee concluded:
This guideline explicitly does not endorse one of the P2Y12 receptor inhibitors over the other.
However, based on data from the trials, the document provides some advice about the selection of the P2Y12 receptor inhibitors in specific situations, and related issues involving clopidogrel resistance.
- Because prasugrel was administered only after PCI had been planned, the writing group “does not recommend that prasugrel be administered routinely to patients with UA/NSTEMI before angiography.”
- The writing group cautions “clinicians about the potential increased bleeding risks associated with prasugrel and ticagrelor compared with clopidogrel in specific settings and especially among the subgroups identified in the package insert and clinical trials.”
- The document reviews at length the issue of clopidogrel resistance, but concludes “there is little information about the use of strategies to select patients who might do better with newer P2Y12 receptor inhibitors.”
- On genotype testing for loss-of-function CYP2c19 alleles: “On the basis of the current evidence, it is difficult to strongly recommend genotype testing routinely in patients with ACS, but it might be considered on a case-by-case basis, especially in patients who experience recurrent ACS events despite ongoing therapy with clopidogrel.”
- On platelet function testing: “Any strong recommendation regarding more widespread use of such testing must await the results” of ongoing trials…. the prudent physician should maintain an open yet critical mind-set about the concept until data are available…”
- On the use of proton pump inhibitors and clopidogrel: “The expert consensus statement does not prohibit the use of PPI agents in appropriate clinical settings, yet highlights the potential risks and benefits from use of PPI agents in combination with clopidogrel.”