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 provide ssome 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.”

Here is the press release from the AHA:

Updated AHA/ACCF guidelines for unstable angina include newest blood thinning drug

Statement Highlights:
  • The blood-thinning drug ticagrelor is now considered equal to blood thinners clopidogrel and prasugrel for treating some patients who have a heart attack or chest pain.
  • Aspirin remains the first line of therapy for patients with NSTEMI heart attacks and unstable angina immediately after hospitalization.
DALLAS, July 16, 2012 – Ticagrelor, a blood-thinning drug approved by the FDA in 2011, should be considered along with older blood thinners clopidogrel and prasugrel for treating patients who are experiencing chest pain or some heart attacks, according to joint updated guidelines issued by the American Heart Association (AHA) Task Force on Practice Guidelines and the American College of Cardiology (ACCF) Foundation.
The “focused update” on unstable angina (chest pain) or a specific kind of heart attack known as non-ST-elevation myocardial infarction (NSTEMI) is published in Circulation: Journal of the American Heart Association and the Journal of the American College of Cardiology. The panel continues to recommend that all patients receive aspirin immediately after hospitalization, continuing as long as it is tolerated. Among the other new recommendations:
  • Patients unable to take aspirin may receive prasugrel for artery-opening procedures since research on the medication is restricted to those patients. Ticagrelor or clopidogrel may be given whether patients receive medical therapy alone or are also having an invasive procedure;
  • Patients undergoing invasive procedures should receive both aspirin and another antiplatelet medication;
  • Patients undergoing medical treatment only should receive aspirin indefinitely and clopidogrel or ticagrelor for up to or at least 12 months.
The AHA and ACCF issue focused updates when pivotal new data are reported that may affect changes to current recommendations and meet specific criteria. One year after the last update, the biggest change is the recommendation to consider ticagrelor as a treatment option in addition to clopidogrel and prasugrel. The panel’s report highlights both the benefits (anti-clotting action) and risks (bleeding) of the new drug.
“We have put it on equal footing with two other antiplatelet medications, clopidogrel and prasugrel,” said Hani Jneid, M.D., lead author of the update and an assistant professor of medicine and director of interventional cardiology research at Baylor College of Medicine, and an interventional cardiologist at the Michael E. DeBakey VA Medical Center in Houston.
Unstable angina occurs when the heart muscle doesn’t get enough blood flow and oxygen because a coronary artery is partially blocked. In NSTEMI, there are also abnormal heart enzymes, indicating that some damage to heart muscle is already occurring.
“These conditions are very common and carry a high risk of death and recurrent heart attacks,” Jneid said. “The AHA and ACCF constantly update their guidelines so that physicians can provide patients with the most appropriate, aggressive therapy with the goal of improving health and survival.” To continue to improve the treatment of these important conditions, the panel encourages clinicians and hospitals to participate in a quality of care data registry designed to track and measure outcomes, complications and adherence to evidence-based recommendations.
“While this focused update of the guidelines provides important guidance to clinicians, our recommendations are not substitutes for a physician’s own clinical judgments and the tailoring of therapy based on individual variability and a patient’s presentation and clinical diagnosis,” Jneid said.
Visit the American Heart Association’s website for information on the signs and symptoms of a heart attack External linkheart attack External link PDF fileunstable angina External link PDF fileanticoagulants and antiplatets External link PDF file andaspirin External link.
Co-authors are Jeffrey L. Anderson, M.D., F.A.C.C., F.A.H.A.,; R. Scott Wright, M.D., F.A.C.C., F.A.H.A.; Cynthia D. Adams, R.N., Ph.D., F.A.H.A.; Charles R. Bridges, M.D., Sc.D., F.A.C.C., F.A.H.A.; Donald E. Casey, Jr, M.D., M.P.H., M.B.A., F.A.C.P., F.A.H.A.: Steven M. Ettinger, M.D., F.A.C.C.; Francis M. Fesmire, M.D., F.A.C.E.P.; Theodore G. Ganiats, M.D.; A. Michael Lincoff, M.D., F.A.C.C.; Eric D. Peterson, M.D., M.P.H., F.A.C.C., F.A.H.A.; George J. Philippides, M.D., F.A.C.C., F.A.H.A.; Pierre Theroux, M.D., .FA.C.C., F.A.H.A.; Nanette K. Wenger, M.D., M.A.C.C., F.A.H.A.; and James Patrick Zidar, M.D., F.A.C.C., F.S.C.A.I. Author disclosures are on the manuscript.

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