ACC-AHA Release Guidelines Update on Unstable Angina-NSTEMI
Updated clinical practice guidelines from the American College of Cardiology (ACC) and the American Heart Association (AHA) for the management of patients with unstable angina/non-ST-segment elevation myocardial infarction (NSTEMI) address a number of important clinical issues including the use of prasugrel, timing of interventions, and the state of current evidence on platelet function testing and genetic testing.
The 2011 focused update was published online March 28, 2011, ahead of print in the Journal of the American College of Cardiology and Circulation.
The writing committee, led by R. Scott Wright, MD, of the Mayo Clinic (Rochester, MN), reviewed the currently available scientific evidence, including several large randomized trials that have been published since the previous version of the guidelines was released in 2007.
Addition of Prasugrel, Support for Early Intervention
In a telephone interview with TCTMD, Jeffrey L. Anderson, MD, of the University of Utah (Salt Lake City, UT), who served as vice chair of the committee, said one of the most important changes to the focused update is the addition of prasugrel to the treatment algorithm.
“Frankly, we were doing a little bit of catch-up because that’s been approved for a while and already had appeared in the 2009 STEMI and PCI focused update, but the issues we incorporated are more specific to unstable angina than for STEMI,” he said, noting that the changes are in agreement with the US Food and Drug Administration (FDA) and endorse prasugrel as an alternative antiplatelet agent in higher risk patients.
The writing group, however, cautions that data on prasugrel come solely from 1 trial, TRITON-TIMI 38, and thus the drug should only be used the way it was in that study—after a decision to proceed to PCI is made.
“It is not our recommendation that prasugrel be administered routinely before angiography, such as in an emergency department, or be used in patients who have not undergone PCI,” the group writes. “The FDA package label suggests that it is reasonable to consider selective use of prasugrel before catheterization in subgroups of patients for whom a decision to proceed to angiography and PCI has already been established for any reason.” However, the writing group did not make specific recommendations about which subgroups of patients might benefit from prasugrel vs. clopidogrel or “explicitly endorse one of the thienopyridines over the other.”
While studies suggest some patients may be resistant to clopidogrel, there is little information about the use of strategies to select patients who might have better outcomes with prasugrel, they add. The committee also suggests that the reversible non-thienopyridine P2Y12 receptor antagonist ticagrelor may play a future role in patients with unstable angina/NSTEMI based on results from the PLATO trial.
The writing group also weighed in on prasugrel in patients who remain hospitalized after unstable angina/NSTEMI and are candidates for CABG, concluding that it should be discontinued at least 7 days prior to a planned surgery.
“There is a significant bleeding risk with this drug,” Dr. Anderson said. “So on average, it takes longer for patients to get back to baseline in terms of their bleeding risk compared with clopidogrel.”
Three trials comparing “early” vs. “delayed” intervention in patients with unstable angina/NSTEMI form the basis of another updated recommendation. Based on results from ISAR-COOL, TIMACS, and ABOARD, together with data from earlier studies, the guidelines committee recommends a strategy of early angiography and intervention to reduce ischemic complications in patients who have been selected for an initial invasive strategy, particularly among those at high risk (defined by a GRACE score > 140).
The “early” time period as defined in the guidelines is considered to be within the first 24 hours after hospital presentation, although the authors stress that there is no evidence that incremental benefit is derived by angiography and intervention performed within the first few hours of hospital admission. A delayed approach is reasonable in low- to intermediate-risk patients, the committee concludes.
“This is a little different than the PCI focused update, which said it is reasonable to treat low-risk patients early,” Dr. Anderson said. “We felt based on the available evidence, which was a subgroup analysis from TIMACS that was not entirely definitive, that it was reasonable to delay.”
GPIs, Diabetes, and Kidney Disease
Regarding glycoprotein IIb/IIIa inhibitors (GPIs), the writing committee based its decision on data from the ACUITY and EARLY ACS trials, concluding that the preponderance of the evidence supports a strategy of selective, rather than provisional, GPI use as part of triple-antiplatelet therapy. They add that use of these agents “may not be supported when there is a concern for increased bleeding risk or in non-high-risk subsets such as those with a normal baseline troponin level, those without diabetes, and those at least 75 years of age, in whom the potential benefit may be significantly offset by the potential risk of bleeding.”
The committee also addressed concerns for patients with diabetes and chronic kidney disease (CKD). Specifically, they changed the recommendation for the use of insulin to control blood glucose in unstable angina/NSTEMI from a more stringent to a more moderate target range in keeping with the 2009 STEMI and PCI focused update and recommend treatment for hyperglycemia greater than 180 mg/dL while avoiding hypoglycemia.
The reason for the change, the group writes, is that they “believed that the 2007 recommendation regarding long-term glycemic control targets failed to reflect recent data casting doubt on a specific ideal goal for the management of diabetes in patients with UA/NSTEMI.”
Although the writing group found “compelling” evidence for adequate hydration preparation for angiography with contrast media in patients with CKD, they concluded that it was insufficient to recommend a specific hydration regimen. They also say the early invasive strategy is “reasonable” in patients with mild and moderate CKD.
“Clinicians should exercise judgment in all populations with impaired kidney function when considering whether to implement an invasive strategy. Such implementation should be considered only after careful assessment of the risks, benefits, and alternatives for each individual patient,” they write. “The observational data with regard to patients with mild to severe CKD also support the recognition that CKD is an underappreciated high-risk characteristic in the UA/NSTEMI population. The increased risk of mortality associated with mild, moderate, and severe CKD remains evident across studies. Indeed, the risks of short- and long-term mortality are increased as the gradient of renal dysfunction worsens.”
The committee also chose to address the issue of platelet function testing and genetic testing in light of the FDA’s ‘black box’ warning that clopidogrel may be less effective in altering platelet activity in patients with a reduced functioning CYP2C19 gene.
Despite a lack of definitive studies and the group’s impression that the level of evidence is low, “we didn’t want to hold back physicians who are concerned about the label change, so we recommend considering it if it would affect management strategy,” Dr. Anderson said. He added that the decision to address genetic testing and platelet function testing was controversial but the committee felt they should be “put on the radar screen.”
Putting It All Together
In a telephone interview with TCTMD, Jeffrey W. Moses, MD, of Columbia University Medical Center (New York, NY), said although it contains nothing “earth-shattering,” focused updates like this are important for keeping abreast of current literature.
“It’s a great place to put it all together and the fact that they synthesize the data is always helpful,” he said. “But it’s important to remember that even within committees like this one, people have different practices. The guidelines try to put things into context for the practitioner but nothing is black and white.”
Wright RS, Anderson JL, Adams CD, et al. 2011 ACCF/AHA focused update of the guidelines for the management of patients with unstable angina/non-ST-elevation myocardial infarction (Updating the 2007 guideline). J Am Coll Cardiol;Circulation.
- Dr. Wright reports no relevant conflicts of interest.
- Dr. Anderson reports serving as a consultant for Bristol-Myers Squibb, Daiichi-Sankyo, Eli Lilly, and Sanofi-Aventis; serving on the speaker's bureau of Schering-Plough; and conducting personal research for AstraZeneca.
- Dr. Moses reports serving as a consultant for Boston Scientific and St. Jude Medical.