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 The recommendations in this focused update are considered current until they are superseded in another focused update or the full-text guideline is revised.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 alongsideprasugrel (Effient) and clopidogrel, 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
- 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/.
STUDY HIGHLIGHTS
- Early hospital care:
- The last version of the guideline recommended the use of clopidogrel in patients with UA/NSTEMI because it was the only US Food and Drug Administration–approved P2Y12 receptor inhibitor.
- The Food and Drug Administration has since approved 2 additional P2Y12 receptor inhibitors for use in patients with UA/NSTEMI: prasugrel and ticagrelor, based on data from head-to-head comparison trials with clopidogrel, in which prasugrel and ticagrelor were respectively superior to clopidogrel in reducing clinical events but at the expense of an increased risk of bleeding.
- Aspirin remains the first line of therapy for patients with UA/NSTEMI and UA immediately after hospitalization.
- Dual antiplatelet therapy with aspirin and either clopidogrel or prasugrel increased the risk for intracranial hemorrhage in several clinical trials and patient populations (especially in those with prior stroke).
- Patients with definite UA/NSTEMI at medium or high risk and in whom an initial invasive strategy is selected should receive dual antiplatelet therapy on presentation.
- Patients undergoing only medical treatment should receive aspirin indefinitely and clopidogrel or ticagrelor for up to or at least 12 months.
- Clinicians should weigh the possible increased risk of intracranial bleeding when considering the addition of ticagrelor to aspirin in patients with prior stroke or transient ischemic attack.
- Clinicians and patients should be cautioned against early discontinuation of P2Y12 receptor inhibitors for elective noncardiac procedures, given the increased hazard of recurrent cardiovascular events from premature discontinuation of P2Y12 inhibitors.
- The expert consensus statement does not prohibit the use of proton pump inhibitors in appropriate clinical settings, yet it highlights the potential risks and benefits from use of proton pump inhibitors in combination with clopidogrel.
- The occurrence of refractory ischemia is associated with a 4-fold increase in the risk for subsequent MI.
- In-hospital care:
- An early invasive strategy (ie, diagnostic angiography with intent to perform revascularization) is indicated in patients with UA/NSTEMI who have refractory angina or hemodynamic or electrical instability (without serious comorbidities or contraindications).
- An early invasive strategy is indicated in initially stabilized patients with UA/NSTEMI (without serious comorbidities or contraindications to such procedures) who have an elevated risk for clinical events.
- For patients in whom an initial conservative strategy is selected and who have recurrent ischemic discomfort with aspirin, a P2Y12 receptor inhibitor (clopidogrel or ticagrelor), and anticoagulant therapy, it is reasonable to add a glycoprotein IIb/IIIa inhibitor before diagnostic angiography.
- It is reasonable to choose an early invasive strategy (within 12 - 24 hours of admission) vs a delayed invasive strategy for initially stabilized high-risk patients with UA/NSTEMI. For patients not at high risk, a delayed invasive approach is also reasonable.
- An early invasive strategy is not recommended in patients with extensive comorbidities (eg, liver or pulmonary failure, cancer), in whom the risks associated with revascularization and comorbid conditions are likely to outweigh the benefits of revascularization.
- An early invasive strategy is not recommended in patients with acute chest pain and a low likelihood of ACS.
- Recommendations for convalescent and long-term antiplatelet therapy:
- For patients with UA/NSTEMI treated medically without stenting, aspirin should be prescribed indefinitely.
- For patients with UA/NSTEMI treated with a stent (bare metal or drug-eluting), aspirin should be continued indefinitely.
- Clopidogrel 75 mg daily, prasugrel 10 mg daily (in PCI-treated patients), or ticagrelor 90 mg twice dailyshould be given to patients recovering fromUA/NSTEMI when aspirin is contraindicated or not tolerated because of hypersensitivity or gastrointestinal intolerance.
- After PCI, it is reasonable to use 81 mg per day of aspirin in preference to higher maintenance doses.
- For patients with UA/NSTEMI who have an indication for anticoagulation, the addition of warfarin may be reasonable to maintain an international normalized ratio of 2.0 to 3.0.
CLINICAL IMPLICATIONS
- In patients with UA/USTEMI who receive medical treatment, aspirin should be given indefinitely and clopidogrel or ticagrelor for at least 12 months.
- An early invasive strategy is recommended in stabilized patients with UA/USTEMI who are at an increased risk for clinical events but have no serious comorbidities.
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