New UA/non-STEMI guidelines highlight new anticoagulants, diagnostic tests, physician decisions

Shelley Wood

August 10, 2007

Washington DC and Dallas, TX - The American College of Cardiology and the American Heart Association have updated their 2002 Guidelines for the Management of Patients with Unstable Angina (UA)/Non-ST-Elevation Myocardial Infarction (NSTEMI), introducing a number of recommendations for initial diagnostic tests, choice and duration of antiplatelet therapy, and new anticoagulants[1] . The new document also highlights strategies and agents that are no longer considered valuable in the treatment or diagnosis of patients with unstable CAD.

The guidelines are published online August 6, 2007 in the Journal of the American College of Cardiology and Circulation.

In an interview with heartwire , writing group chair Dr Jeffrey Anderson (University of Utah Hospital, Salt Lake City) highlighted some of the key changes in the updated guidelines.

"There have been a lot of new trials, new drugs, new anticoagulants, and new issues, so there are a moderate number of changes," he said. "I don't think there are a lot of things that are completely reversed, but there's certainly been an evolution and fine-tuning of the 2002 guidelines."

One of the overarching themes, according to Anderson, is a slight pullback in terms of the emphasis on an initial invasive strategy for all UA/NSTEMI patients. "In these guidelines we've sort of swung the pendulum back a little bit from the initial invasive strategy from 2002," he said. Instead, the 2007 update urges physicians to first establish whether patients are high or low risk and then apply the guidelines according to that initial risk assessment. "In low-risk patients, particularly low-risk women, an initially conservative strategy is more appropriate. . . . Low-risk patients should first be noninvasively risk-stratified and treated medically, but not all sent to the lab." Based on the ICTUS trial, the guidelines also state that an initially conservative strategy can also be considered in stabilized patients, he said

But Dr Eric Peterson (Duke University, Durham, NC), another member of the writing group, sees this slightly differently. "I take it almost the other way around," he told heart wire . "The guidelines give a 1a recommendation for use of an early invasive strategy in patients who match any of these risk factors, including those who have positive markers, but there is some latitude that's given to physicians—a 2b recommendation—that they can consider a conservative strategy if they initially stabilize the patient."

Peterson acknowledged there was "tension inside the guideline committee" about how to balance some of the conflicting trials in this area—for example, ICTUS vs ISAR-COOL or TACTICS-TIMI 18. "When it comes to the issue of invasive vs conservative strategies, there is evidence that goes both ways, depending on which study you choose to look at. . . . Following that evidence, there are differences in clinician opinion as to what the right strategy would be, and I think in part the guidelines reflect that."

What the guidelines do urge, says Peterson, is for physicians to first make the decision as to what treatment strategy they're going to take, then follow the recommended pathways according to what they've decided. "These guidelines give clinicians the mandate to make that decision up front and then to tailor the therapy that would go along with that, depending on what strategy you choose."

In with the new, out with the old

As expected, bivalirudin and fondaparinux have made it into the 2007 update. Both agents have a class 1 indication for use on top of antiplatelet therapy for patients in whom an invasive strategy is selected. Unfractionated heparin (UFH) and enoxaparin are given class 1 indications in patients undergoing an invasive strategy or a conservative strategy, but fondaparinux is preferred over these other agents in patients at an increased risk of bleeding for whom a conservative strategy is selected. In UA/NSTEMI patients for whom an initial conservative strategy is selected (with the possibility of converting to an invasive strategy other than CABG), enoxaparin or fondaparinux are recommended over UFH.

Also new to the guidelines are recommendations for the use of multislice CT angiography and cardiac MRI, reflecting other recent appropriateness criteria and scientific statements dealing with imaging. Brain-type natriuretic peptide (BNP) makes its debut in the updated guidelines as a biomarker test that can be considered to supplement global risk assessment in ACS patients. Otherwise, a cardiac-specific troponin is now recommended as the "preferred marker."

"Troponin has continued to rise and really everything else has fallen way behind," Anderson explained. "In 2002, there was more attention paid to alternative markers; now we've sort of pushed those down the list."

Other notable changes or tweaks in the 2007 update include a fresh emphasis on reducing delays to initial evaluation and facilitated emergency-department (ED) diagnosis and triage, including the use of a 12-lead ECG ideally within 10 minutes of ED arrival. For patients treated invasively, recommended duration of clopidogrel therapy has been extended. "The guidelines now recommend that clopidogrel therapy be continued for at least one year after drug-eluting stent placement and ideally up to one year with a bare-metal stent or even with medical therapy, because we think the additional antiplatelet therapy seems to be beneficial," Anderson commented.

The new guidelines also give the option of using a higher loading dose of clopidogrel. "A lot of the more recent studies use 600 mg, and even though we need more studies in terms of larger numbers and hard outcomes, those studies look very promising. So we offer that as an option," Anderson said.

According to Anderson, recommendations for GP IIb/IIIa inhibitors are largely unchanged from the 2002 guidelines. "The only thing that's come along is whether, with high-risk ACS patients, you can just give clopidogrel alone without adding a GP IIb/IIIa inhibitor," Anderson explained. "There's one study that has showed that adding on a GP IIb/IIIa inhibitor did seem to benefit patients, so in higher-risk patients we're still suggesting you use a GP IIb/IIIa inhibitor if you're doing an invasive strategy, even if you're using clopidogrel. In the lower-risk patients, you can use either one or the other; at least one and possibly both."

Finally, the guidelines also drive the final nail into the coffin for strategies that have proved nonbeneficial or harmful over the past five years, including the use of supplements such as beta-carotene, vitamins E and C, and folic acid. Also singled out as harmful in the new guidelines are hormone-replacement therapy in postmenopausal women and the use of nonsteroidal anti-inflammatory drugs (NSAIDs), except for ASA, for UA/NSTEMI patients during hospitalization.

"If one looks at what has happened over the past five to 10 years, adverse outcomes in NSTEMI have really fallen dramatically," Anderson said. "The bottom line is, the guidelines seem to be working. In the past 10 years we've pushed the envelope in terms of evidence-based medicine for diagnostics and treatment, and we do seem to be having an impact on the risks associated with ACS. With that in mind, the message would be to push ahead and fine-tune what we do and hopefully get even better outcomes."

In the paper, Anderson disclosed receiving research grants from AstraZeneca and Bristol-Myers Squibb; being on the speakers' bureau for Merck; and acting as a consultant/advisor for Bristol-Myers Squibb, Merck, Sanofi, and ThromboVision. Peterson disclosed receiving research grants from Bristol-Myers Squibb/Sanofi, Millennium, and Schering-Plough and being on the speakers' bureau for Millennium and Schering-Plough.


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