Skip to main content

Guidelines Updated for Unstable Angina/Non-ST Elevation Myocardial Infarction


CLINICAL CONTEXT

According to the current study by Jneid and colleagues, new evidence is available on the management of unstable angina. This report replaces the 2007 American College of Cardiology Foundation/American Heart Association (ACC/AHA) Guidelines for the Management of Patients With Unstable Angina/Non–ST-Elevation Myocardial Infarction (UA/NSTEMI) that were updated by the 2011 guidelines.
This guideline was reviewed by 2 official reviewers each nominated by the ACCF and the AHA, as well as 1 or 2 reviewers each from the American College of Emergency Physicians; the Society for Cardiovascular Angiography and Interventions; and the Society of Thoracic Surgeons; and 29 individual content reviewers, including members of the ACCF Interventional Scientific Council. The recommendations in this focused update are considered current until they are superseded in another focused update or the full-text guideline is revised. Guidelines are official policy of both the ACCF and the AHA.

STUDY SYNOPSIS AND PERSPECTIVE

American cardiology societies have caught up with the European Society of Cardiology by issuing their second update to the UA/NSTEMI guidelines in 18 months, with the 2012 focused update replacing the 2011 guidelines [1]. The new recommendations include ticagrelor (Brilinta) as one of the options for antiplatelet therapy alongside prasugrel (Effient) andclopidogrel, bringing them in line with European guidance issued last September.
The European guidance, however, gave precedence to the new antiplatelets over clopidogrel, whereas the American update "places ticagrelor on an equal footing with the other two antiplatelets available--this is the main reason for the update," lead author Dr Hani Jneid (Baylor College of Medicine, Houston, TX), told heartwire . "Doctors now have a choice for second-line therapy after aspirin, depending on the patient's clinical scenario, physician preference, and cost," because the latter will come into play now that clopidogrel is available generically, he noted.
The US decision to recommend first prasugrel--in its 2011 update to the UA/NSTEMI guidelines--and now ticagrelor as equivalent antiplatelet therapy choices to clopidogrel after aspirin puts it somewhat at odds with the Europeans, who reserve clopidogrel use for those who cannot take the newer agents.
But Jneid says the Americans have their reasons for this differing stance. While it is "biologically plausible" to recommend ticagrelor and prasugrel in preference to clopidogrel--"because they are faster acting and more potent"--the cost-effectiveness of the new agents is not known, he says. Nor is it clear how the efficacy observed in pivotal clinical trials of these agents is going to translate into real-world benefit, he says, adding that issues such as bleeding with prasugrel and compliance with a twice-daily drug such as ticagrelor remain concerns.
Bulk of 2012 Update on How to Use Ticagrelor
The 2012 ACCF/AHA focused update for the management of UA/NSTEMI stresses that all patients at medium/high risk should receive dual antiplatelet therapy on admission, with aspirin being first-line, indefinite therapy.
The bulk of the update centers on how to use ticagrelor which--like prasugrel or clopidogrel--can be added to aspirin for up to 12 months (or longer, at the discretion of the treating clinician). Jneid notes it's important to remember that prasugrel can only be used in the cath lab in patients undergoing percutaneous coronary intervention (PCI), whereas ticagrelor, like clopidogrel, can be used in medically managed or PCI patients.
And he emphasizes that, in line with the FDA's black-box warning on ticagrelor, this new antiplatelet agent must only be administered with a "baby" dose of aspirin (81 mg in the US).
The 81-mg aspirin dose is also considered a reasonable option in preference to a higher maintenance dose of 325 mg in any acute coronary syndrome (ACS) patient following PCI, he adds, as this strategy is believed to result in equal efficacy and lower bleeding risk.
With regard to how long antiplatelet therapy should be stopped before planned cardiac surgery, the recommendation is five days for ticagrelor--the same as that advised for clopidogrel. For prasugrel, the guidance is to stop therapy seven days prior to surgery.
Jneid also highlights other important recommendations from the 2011 focused update carried over to 2012:
It is "reasonable" to proceed with cardiac catheterization and revascularization within 12–24 hours of admission in initially stable, very high-risk patients with ACS.
An invasive strategy is "reasonable" in patients with mild and moderate chronic kidney disease.
In those with diabetes hospitalized with ACS, insulin use should target glucose levels <180 mg/dL, a less-intensive reduction than previously recommended.
Platelet function or genotype testing for clopidogrel resistance are both considered "reasonable" if clinicians think the results will alter management, but it is acknowledged that "there is not much evidence to support these assays," says Jneid.
Committee Encourages Participation in Registries
Jneid observes that unstable angina and NSTEMI are "very common" conditions that carry a high risk of death and recurrent heart attacks, which is why "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 this end, he notes that the writing panel encourages clinicians and hospitals to participate in quality-of-care registries designed to track and measure outcomes, complications, and adherence to evidence-based medicines.
Conflicts of interest for the writing committee are listed in the paper.
References
  1. Jneid H, Anderson JL, Wright SR, et al. 2012 ACCF/AHA focused update on the guideline for the management of patients with unstable angina/non-ST elevation myocardial infarction (Updating the 2007 guideline and replacing the 2011 focused update): A report of the ACCF/AHA. Circulation 2012;DOI: 10.1161/CIR0b013e3182566fleo. Available at:http://circ.ahajournals.org/.

Comments

  1. Darius8 May 2014 at 00:23

    I am a medical resident on cardiology and I also wrote a few words about unstable angina.

    ReplyDelete

Post a Comment

Popular posts from this blog

Missing Data Lead FDA Panel to Vote Against Rivaroxaban for ACS May 23, 2012 (Updated May 24, 2012) (Silver Spring, Maryland) — The missing data issues plaguing the ATLAS ACS 2 TIMI 51 trial of the factor Xa inhibitor rivaroxaban (Xarelto, Bayer Healthcare/Janssen Pharmaceuticals) have prevented the drug from earning the endorsement of the FDA Cardiovascular and Renal Drugs Advisory Committee. At its May 23 meeting, the panel voted six to four (with one abstention) against recommending that the FDA approve rivaroxaban for reducing the risk of thrombotic cardiovascular events in patients with acute coronary syndrome or unstable angina in combination with aspirin, aspirin plus clopidogrel, or ticlopidine. Janssen's application is based on the results of the ATLAS ACS 2 phase 3 and the ATLAS ACS TIMI 46 phase 2 trial. The placebo-controlled ATLAS ACS 2 showed rivaroxaban reduced the risk of both all-cause and cardiovascular mortality while increasing the risk of bleeding and intracranial hemorrhage, but the studies were hindered by early patient withdrawals and missing data. We Don't Know What We're Missing Based on the ATLAS ACS 2 results, FDA reviewer Dr Karen Hicks recommended approval of rivaroxaban for the requested indications except all-cause mortality. However, another FDA reviewer, Dr Thomas Marciniak, was adamant that the trial results are not interpretable because about 12% of the patients had incomplete follow-up, far higher than the 1% to 1.5% differences in the end-point rates between rivaroxaban and placebo. A total of 1294 subjects discontinued the trial prematurely, and the company was only able to contact 183, of which 177 were confirmed to be alive. Because of the patient dropouts, the company adopted a "modified intention-to-treat analysis," whereby patients were observed for 30 days after randomization or the global end date for the trial, instead of observing all the patients until the end of the trial as the FDA originally suggested. Marciniak criticized the sponsor's efforts to follow the patients and said that three patient deaths not counted in the modified intention-to-treat analysis may just be the "tip of the iceberg." Because the percentage of patients whose ultimate vital status remains unknown is much greater than the reported differences in mortality rates, the claimed mortality benefits are not reliable. The majority of the panel sided with Marciniak. For example, Dr Sanjay Kaul (University of California, Los Angeles) voted "no" because "there was enough uncertainty in the quality and robustness of the data that dissuaded me from voting yes. . . . The 'missingness' of the data doesn't invalidate it, but it certainly makes it hard to infer [the conclusion]." Dr Steven Nissen (Cleveland Clinic, OH) said that the decision to use the modified intention-to-treat analysis had a "profound impact" on the interpretability of the data. "It's saying we don't care what happens after 30 days, [and] that colored the trial in ways we couldn't recover from." Given the risk of major bleeding, "I want to see better evidence that this strategy of adding an Xa inhibitor or a direct thrombin inhibitor or something else to a good antiplatelet agent is robustly better for the patient," Nissen said. He recommends that the companies run a new trial of the 2.5 twice-daily dose of rivaroxaban using a strict intention-to-treat approach, but, he said, "I don't expect the death benefit to be too robust." Several panelists said they were concerned that the patients who dropped out of the trial were disproportionately likely to have a bleeding event, which led them to quit the trial, or a "protopathic" event, as statistician Dr Scott Emerson (University of Washington, Seattle) put it. "We're worried that an impending event is what is changing their behavior. We see that all the time in clinical trials--that regularly measured end points do not pick up [all of] the events," he said. He said that since the company was only able to contact 183 of the over 1200 patients who dropped out, it is possible that the dropouts skew the outcomes comparison of the trial. "Differential event rates after dropout are the number-one thing we're afraid of, so you have to explore it" in a statistical sensitivity analysis of the potential impact of these unknown outcomes. "It would not surprise me if, at the end of the day, these data did not hold up under a proper sensitivity analysis," he said. "What I want to know is, among the people who had events, how differential was the follow-up, but I can tell you by just looking at it, there was a very slightly different amount of follow-up of the people in the treatment arm. But I don't know whether everyone in the treatment arm was cured and they were trekking in the Himalayas and everyone in the placebo arm went home to die. I don't know that that's not the case." Dr Maury Krantz (University of Colorado, Denver) voted in favor of approval but said he does not know how rivaroxaban would perform in general clinical practice, especially when used with aspirin and clopidogrel. "I felt very much torn by this. This isn't a simple paradigm shift. It means going to triple therapy, which is really a three-headed monster in many ways. I think that what you're going to see in practice, if this is not done carefully with the proper labeling and secondary studies, is really dramatic magnification of bleeding and perhaps minimization of the efficacy benefit."

May 23, 2012   (Updated May 24, 2012)  (Silver Spring, Maryland)  —  The missing data issues plaguing the  ATLAS ACS 2 TIMI 51   trial of the factor Xa inhibitor  rivaroxaban  (Xarelto, Bayer Healthcare/Janssen Pharmaceuticals) have prevented the drug from earning the endorsement of the  FDA  Cardiovascular and Renal Drugs Advisory Committee. At its May 23 meeting , the panel voted six to four (with one abstention) against recommending that the FDA approve rivaroxaban for reducing the risk of thrombotic cardiovascular events in patients with acute coronary syndrome or unstable angina in combination with aspirin, aspirin plus  clopidogrel , or  ticlopidine . Janssen's application is based on the results of the ATLAS ACS 2 phase 3 and the  ATLAS ACS TIMI 46   phase 2 trial. The placebo-controlled ATLAS ACS 2 showed rivaroxaban reduced the risk of both all-cause and cardiovascular mortality while increasing the ri...
Post a Comment
Read more

Antidepressants Linked to Higher Diabetes Risk in Kids

Pediatric patients who use antidepressants may have an elevated risk for type 2 diabetes, the authors of a new study report. In a retrospective cohort study of more than 119,000 youths 5 to 20 years of age, the risk for incident type 2 diabetes was nearly twice as high among current users of certain types of antidepressants as among former users, Mehmet Burcu, PhD, and colleagues report in an article  published online October 16 in  JAMA Pediatrics . The risk intensified with increasing duration of use, greater cumulative doses, and higher daily doses of these antidepressants. The findings point to a growing need for closer monitoring of these products, including greater balancing of risks and benefits, in the pediatric population, the authors caution. They undertook the study because, despite growing evidence of an association between antidepressant use and an increased risk for type 2 diabetes in adults, similar research in pediatric patients was scarce. "To our know...
Post a Comment
Read more

EHR Work Measures Proposed to Address Burnout

Electronic health record (EHR) vendors should imbed metrics into their systems to measure how EHRs affect clinicians' work, experts write in a commentary  published online  October 10 in the  Annals of Internal Medicine . Yumi T. DiAngi, MD, a fellow in clinical informatics at Stanford University School of Medicine in Palo Alto, California, and colleagues propose six areas metrics should cover and recommended the creation of a "national council of clinicians" to design measures and create guidelines to address privacy and other issues. "The EHR, which was intended to improve patient care, has had the ironic and unintended consequence of impairing practice efficiency, largely because of poor design, a focus on regulatory reporting, and the burden placed on clinicians by data entry," they write. EHRs have also led to high levels of burnout as physicians' satisfaction in their work has declined, they note. To gain insight into the stresses that have pro...
Post a Comment
Read more