UA/NSTEMI Guidelines Add Prasugrel, Quicker Angiography


The American College of Cardiology Foundation and the American Heart Association have published updated guidelines for managing patients with unstable angina/non–ST elevation myocardial infarction, taking into consideration the use of a newer agent, prasugrel, as an alternative to clopidogrel, and recommending diagnostic angiography sooner for patients at high risk, among other changes.

The guidelines (Am. J. Cardiol. 2011 March 28 [doi:10.1016/j.jacc.2011.02.009]) are based on the most recent clinical trial evidence available., They update recommendations from 2007, and include several changes clinicians should be aware of, the guidelines' lead author, Dr. R. Scott Wright of the Mayo Clinic in Rochester, Minn., said in an e-mail interview. These are, in order of importance:

▸ The timing of invasive therapy in medium- and high-risk patients.

▸ The role of triple- vs. dual-antiplatelet therapy in patients at medium and high risk.

▸ The role of invasive therapy in patients with chronic kidney disease.

▸ The importance of participating in quality improvement processes.

▸ The role of prasugrel in non–ST elevation acute coronary syndrome.

Clinicians face tough decisions about when to use an invasive strategy such as diagnostic coronary angiography – whether within hours of presentation or days, Dr. Wright and his colleagues wrote in their analysis. Immediate catheterization with revascularization of unstable coronary lesions may prevent ischemic events that would otherwise occur during medical therapy – but pretreatment with antithrombotics “may diminish thrombus burden and 'passivate' unstable plaques,” improving the safety of the procedure and reducing the risk of ischemic complications.

The new guidelines, based on three randomized controlled trials evaluating the timing of angiography, recommend an early invasive strategy (12-24 hours after presentation) over a delayed invasive strategy (more than 24 hours after presentation) for initially stabilized high-risk patients with UA/NSTEMI.

“For patients not at high risk, a delayed invasive approach is also reasonable,” Dr. Wright and his colleagues wrote.

Several changes to earlier recommendations for antiplatelet therapy are contained in the new guidelines, including altered loading doses for clopidogrel to counter the potential for the drug to be less effective in some patient groups, and the addition of prasugrel, which was approved by the Food and Drug Administration after the last guidelines were published.

Prasugrel, in a randomized controlled trial comparing it with clopidogrel, was shown to be superior in reducing clinical events but at the expense of an increased risk of bleeding, the guideline writers noted. In March 2010 the FDA issued a warning that in some patient groups clopidogrel is less effective than it should be because of a genetic variant that inhibits the body's conversion of the prodrug to the drug.

However, Dr. Wright and his colleagues stopped short of endorsing prasugrel as a first choice over clopidogrel because of the higher bleeding risk and other considerations. People aged 75 years or older, those with a history of transient ischemic attack or stroke or with active pathological bleeding, and people weighing less than 60 kg saw no benefit and/or net harm from prasugrel, they noted.

Dr. Wright and his colleagues also changed recommendations involving glycoprotein IIB/IIIa inhibitors, noting that recent studies “more strongly support a strategy of selective rather than provisional use of GP IIb/IIIa inhibitor therapy as part of triple-antiplatelet therapy,” due to concerns about the potential bleeding risks.

Dr. Wright declared no conflicts of interest. Several of Dr. Wright's coauthors, including Dr. Jeffrey L. Anderson, the writing committee's vice chair, disclosed consultant relationships with pharmaceutical firms Sanofi-Aventis, Bristol Myers-Squibb, Lilly, and Daiichi. Members with conflicts were not permitted to vote on recommended drug therapies.

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