Updated UA/NSTEMI Guidelines Make Room for Prasugrel

March 29, 2011

March 29, 2011 (Washington, DC and Dallas, Texas) — The American College of Cardiology and the American Heart Association have updated the 2007 Guidelines for the Management of Patients with Unstable Angina (UA)/Non-ST-Elevation Myocardial Infarction (NSTEMI), with the new document intended to provide further guidance on the use of antiplatelet and anticoagulant therapy [1].

The writing group makes a number of recommendations, including recommendations on the timing, duration, and use of dual antiplatelet therapy and triple antiplatelet therapy in high-risk patients. Most notably, the group notes that another thienopyridine, that being prasugrel (Effient, Eli Lilly/Daiichi Sankyo), is now available in addition to clopidogrel (Plavix, Bristol-Myers Squibb/Sanofi-Aventis).

"There's always a lot of activity these days with the antithrombotic agents, and we're sort of doing a little catch-up, to be perfectly honest with you," Dr Jeffrey Anderson (University of Utah, Salt Lake City), the vice-chair of the updated guidelines, told heartwire . "Basically, when you look at the focused update, a lot of it has do with prasugrel and the timing on interventions, as well as special groups, such as having more information on patients with chronic kidney disease and diabetic patients. Prasugrel has been included in the guidelines and is pretty much consistent with the Food and Drug Administration label."

Making Room for Prasugrel in UA/STEMI

Prasugrel was granted approval during PCI in the setting of ACS, an approval that was based primarily on the strength of the TRITON-TIMI 38 trial, a study that compared prasugrel with clopidogrel in 13 608 patients with moderate- to high-risk unstable angina, STEMI, or NSTEMI. As reported previously by heartwire , prasugrel significantly reduced ischemic events compared with clopidogrel, but at the expense of an increase in major (and fatal) bleeding in ACS patients scheduled for PCI.

Anderson told heartwire that the guidelines emphasize that prasugrel be started at the time of angiography--when a decision is made to perform angioplasty rather than surgery--and that it is not recommended for patients undergoing conservative, noninvasive management. In patients managed noninvasively, clopidogrel, loading dose followed by the maintenance dose, should be added to aspirin and anticoagulant therapy as soon as possible after admission and administered for at least one month. He added that the use of prasugrel on presentation is discouraged--although it is allowed, with a class IIb recommendation, based on the FDA label--but has a class I recommendation for use at the time of catheterization. Clopidogrel and prasugrel should both be given for at least 12 months following PCI. In terms of stopping prasugrel if the patient needs to go to surgery, based on the current guidelines, the drug should be stopped for at least seven days because of the increased bleeding risks.

"Prasugrel has been on the market for a while now, and this is in the FDA label, so this is not anything dramatic," said Anderson.

GP IIb/IIIa Inhibitors, Diabetes, and CKD

In addition, the writing group makes a new recommendation of the use of upstream glycoprotein (GP) IIb/IIIa inhibitors, stating the drugs can be considered in high-risk UA/NSTEMI patients already taking aspirin and a thienopyridine and who are selected for an invasive strategy. Such high-risk patients include those with elevated troponin levels, diabetes, or significant ST-segment depression, but who are not at an increased risk for bleeding. In UA/NSTEMI patients at low risk for ischemic events, such as those with a TIMI risk score <2 or those at high risk of bleeding, who are already treated with aspirin and clopidogrel, the upstream use of GP IIb/IIIa inhibitors is not recommended.

The group notes that there are many high-risk UA/NSTEMI patients where an invasive strategy would be preferred to conservative medical management, including those with mild to moderate kidney disease. For patients on dialysis or those with end-stage renal disease, the data are not sufficient to recommend catheterization and even suggest some harm. Similarly, an invasive strategy is preferred among diabetic patients, said Anderson, with data suggesting these patients fare better when treated invasively rather than with conservative therapy.

Regarding the interindividual variability in response to clopidogrel, platelet genotype assessment and platelet-function testing have a class IIb recommendation, with experts arguing for a "selective, limited approach" to their use. The recommendation is meant to provide some wiggle room for clinicians, alerting them to the importance of the issue, without putting too much unnecessary burden on them, as well as on insurers and society, to put these strategies in place. The selective, limited approach is "prudent" until more evidence comes in.

And finally, the authors note there is less emphasis on specific types of contrast agents, instead stressing that physicians should be conscious of the volume of contrast used during procedures and that patients should be adequately hydrated prior to undergoing angiography to avoid the risk of contrast-induced nephropathy.

Anderson reports consulting for Bristol-Myers Squibb, Daiichi-Sankyo, Eli Lilly, and Sanofi-Aventis; is part of the AstraZeneca speaker's bureau; and has performed personal research involving AstraZeneca. Disclosures for the coauthors are listed in the paper.

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