2014 NSTE-ACS Clinical Practice Guidelines -- What's New?

Approximately 30% of patients presenting with acute coronary syndrome (ACS) have ST-segment elevation myocardial infarction (MI), and the remainder unstable angina or non--ST-segment elevation (NSTE) MI. Because the presentations of unstable angina and NSTE MI are similar, the guideline authors of new practice guidelines updated their terminology to NSTE ACS, rather than UA/NSTE MI, to reflect this similarity. This complete revision replaces the 2012 ACCF/AHA focused update incorporated into the 2007 ACCF/AHA guidelines.¹ In general, the approach to the patient remains unchanged: risk stratify, select an initial management strategy, complete the diagnostic evaluation for MI, use medical therapy and revascularization in appropriate patients, and initiate secondary prevention therapies.

Selected differences between the 2012 combined guideline and the 2014 are described below. Notably, the authors are to be commended for including new Class I recommendations for patient discharge instructions as well as the recommendation for a plan of care for smooth transitions and systems to promote care coordination. These clear instructions include specific recommendations for patient education regarding cardiovascular risk factors (blood pressure, cholesterol levels, lifestyle modification such as exercise and smoking cessation, medications, management of recurrent angina, cardiovascular risk factors, and activity levels. The hospital readmission rate for ACS remains high and having an organized well-written plan of attack helps hospitals and clinicians take the initiative to implement multidisciplinary teams to “attack” the problem.

Diagnosis of myocardial infarction

1. A class III recommendation: No benefit is given for CK-MB assay for diagnosis of MI when using contemporary troponin assays and measurement should be reserved for estimation of infarct size.
2. The diagnosis of myocardial infarction is made when the troponin rises or falls. If the initial troponin is elevated (defined as greater than the 99th percentile of the upper value of the reference range), the diagnosis is made if a ≥ 20% rise or fall in subsequent troponins occurs.
3. Although no specific recommendation is made with respect to use of point-of-care troponins, their lower specificity is acknowledged and central laboratory testing is favored in addition to initial point-of-care testing.
4. A class IIb recommendation is made to remeasure troponin on day 3 or 4 to ascertain infarct size.
5. A class IIb recommendation is made to add B-type natriuretic peptide (BNP) as an additional prognostic tool.

Risk stratification

6. A class IIa recommendation is given for coronary CT angiography in patients with possible ACS, a normal 12-lead ECG, negative troponins, and no history of coronary artery disease CAD.
7. The term “ischemia-guided strategy” replaces “initial conservative management.” An ischemia-guided approach is recommended for patients with a low-risk score (TIMI 0 or 1, GRACE < 109).
8. The early invasive strategy recommendations are stratified by timing:
   1. Immediate (within 2 hours): Patients with refractory or recurrent angina with initial treatment, signs/symptoms of heart failure, new/worsening mitral regurgitation, hemodynamic instability, sustained ventricular tachycardia, or ventricular fibrillation
   2. Early (within 24 hours): None of the immediate characteristics but new ST-segment depression, a GRACE risk score > 140, or temporal change in troponin
   3. Delayed invasive: None of the immediate or early characteristics but renal insufficiency, left ventricular ejection fraction (LVEF) < 40%, early post-infarct angina, history of percutaneous coronary intervention (PCI) within the past 6 months, prior coronary artery bypass surgery (CABG), GRACE risk score of 109-140, or TIMI score of 2 or higher.

Medical Therapy

9. Angiotensin-converting enzyme (ACE) inhibitors: a slight change in level of recommendation was made. The guidelines clarify that an ACE inhibitor is a class I recommendation for patients with stable chronic kidney disease (CKD) in addition to patients with LVEF < 40%, those with hypertension (HTN), heart failure, or diabetes mellitus (DM). The recommendation for patients without a class I indication and NSTE ACS (for example in patients with an LVEF > 40% without CKD, HTN or DM) was downgraded from a class IIa recommendation in prior ACS guidelines to a IIb recommendation in all other patients with cardiac or vascular disease. While data from meta-analyses of ACE inhibitor trials reporting outcomes in the subgroup of patients without heart failure or systolic dysfunction report a mortality benefit,² more recent data from the observational REACH registry of patients with stable CAD did not find a benefit for ACE inhibitors taken with other standard pharmacotherapy in reducing CV events.³ There are no specific randomized trials that evaluated hard outcomes with ACE inhibitors in NSTE ACS in patients without heart failure or low EF.
10. For early initial oral antiplatelet therapy, ticagrelor is given a class IIa recommendation over clopidogrel. In the prior guidelines, either ticagrelor or clopidogrel was a Class I recommendation with clopidogrel carrying a higher level of evidence rating. A recent analysis of subgroup data from NSTE ACS patients enrolled in the PLATO trial found that the benefit of ticagrelor was consistent with main study findings and independent of primary management strategy. The rate of PLATO-defined major bleeding was similar and non-CABG major bleeding increased with ticagrelor compared to clopidogrel.⁴
11. Prior to PCI, both ticagrelor and prasugrel are given Class IIa recommendations over clopidogrel, consistent with the findings of the PLATO and TRITON-TIMI 38 trials. This is an added recommendation based upon the newer evidence classification adopted by the ACC/AHA. In additional prasugrel, but not clopidogrel or ticagrelor, carries a caveat that it should only be selected in patients who are not at high risk for bleeding complications secondary to the increased risk of spontaneous, life-threatening, and fatal bleeding compared to clopidogrel in TRITON-TIMI 38. While not described in the guidelines, Wiviott et al reported post-hoc findings of enhanced efficacy and lower bleeding rates in a core cohort patients less than 75 years of age, weighing 60 kg or more and with no history of stroke or transient ischemic attack.⁵
12. The recommendation for dual antiplatelet therapy (DAPT) remains 12 months (Class I recommendation) for both bare metal (BMS) and drug-eluting stents (DESs). Consideration can be given (Class IIb recommendation) for a longer duration of DAPT for patient receiving a DES. This is an area of intensive research. To date, there are no results in randomized trials comparing the duration of DAPT specifically in patients with ACS. Most trials suggesting the potential for shorter durations of therapy have been using specific newer generation stents in all-comers undergoing PCI.⁶ More information in this area, primarily from observational studies, is expected within the next two years.
13. If the patient has received a loading dose of clopidogrel 300 mg and is undergoing PCI, a second 300-mg dose should be administered prior to PCI.
14. Bivalirudin is given a Class IIa recommendation over unfractionated heparin plus a glycoprotein IIb/IIIa receptor antagonist for PCI in patients at high-risk of bleeding, including older patients.
15. No formalized method of assessing bleeding risk in the hospital or post-hospitalization period is suggested.
16. Clarified that in the setting of ACS, aspirin should be continued/administered prior to CABG (and clopidogrel, ticagrelor be discontinued).
17. No specific guidance is given for length of DAPT for patients receiving triple oral antithrombotic therapy with warfarin other than to say that the duration should be “minimized” as there are insufficient randomized trial data. The Class IIb recommendation for an INR target of 2.0-2.5 in patients taking warfarin remains despite no prospective trials on the practice. Practitioners interested in this topic may refer to the recently released European Society of Cardiology guidelines for management of antithrombotic therapy in patients with ACS undergoing PCI or valve procedures.⁷
18. The use of a proton pump inhibitor (PPI) is recommended for patients receiving triple oral antithrombotic therapy. Mention is made that the FDA recommends avoiding esomeprazole and omeprazole specifically and that the data to suggest increased harm are weak. A PPI is also recommended if an NSAID is used with DAPT.
19. Given the explosion of narcotic use within the U.S. and noted risks of NSAIDs in the post-MI patient, the guideline writers addressed pain management for the patient with ACS at the time of hospital discharge by recommending careful assessment of the patient’s need for chronic therapy and a recommendation that a stepped approach be taken with acetaminophen and nonacetylated salicylates (such as choline magnesium trisalicylate, salsalate) or tramadol be prescribed before prescribing small doses of narcotics. If small doses of narcotics are not effective, nonselective NSAIDs such as naproxen are recommended. The use of COX-2 selective agents is reserved as last-line pain management.
20. A Class III recommendation: No benefit, is given to the use of folic acid, vitamins E, C, and beta carotene for secondary prevention. Despite reducing homocysteine levels, the combination of folic acid and vitamin B12 taken following MI failed to reduce the risk of recurrent CVD events, stroke, mortality, and cancer diagnoses compared to placebo in the SEARCH trial.⁸ Given the potential for decreased medication adherence with numbers of pills taken, we should encourage patients to discontinue taking these agents for preventative care.

Special Populations

Women:

21. A class III recommendation: No benefit, is given for an early invasive strategy in women presenting with low-risk features. This recommendation is based upon the AHRQ report stating that there were limited data in UA and NSTE MI comparing an invasive versus ischemia-driven revascularization strategy in women with ACS to confirm benefit and one meta-analysis reporting an increase in death or MI in biomarker-negative women undergoing an early invasive strategy.^9,10

Older Persons:

22. CABG is given a Class IIa recommendation over PCI in patients 75 years of age and older who are appropriate candidates (particularly those with DM, SYNTAX score of 22 or higher), with or without LAD involvement. Suspected Cocaine or Methamphetamine Intoxication
23. Management strategies for patients with suspected cocaine or methamphetamine intoxication are provided. Signs of acute intoxication such as euphoria, tachycardia, and/or HTN) should be identified and, if present, benzodiazepines alone or in combination with nitroglycerin is given a Class IIa recommendation while beta-blockers are given a Class III recommendation: Harm and should be avoided due to risk of coronary vasospasm. If no signs of acute intoxication are present, patients with a history of cocaine or methamphetamine use should be treated identically to other patients (Class I indication).

Stress Cardiomyopathy

24. In patients presenting with stress (Takotsubo) cardiomyopathy, conventional secondary prevention medications of ACE inhibitors, beta-blockers, and aspirin, as well as symptomatic relief using diuretics, are recommended (Class I recommendation). Oral anticoagulation is recommended for patients with LV thrombi (Class I recommendation) and as stroke prophylaxis (duration not specified) (Class IIb recommendation).

Patients with Asymptomatic Anemia

25. The risks of routine blood transfusion are addressed. A Class III recommendation: No benefit, is given for routine blood transfusion for hemodynamically stable patients with hemoglobin level of 8 g/dL or higher. While most observational data suggest no mortality benefit associated with transfusion in patients with higher hemoglobin values, this recommendation does not endorse transfusion for patients with lower hemoglobin values as no prospective randomized data exist in patients with MI. A recent study of transfusion practices across 57 hospitals in almost 35,000 patients presenting with MI used propensity modeling for 45 patient characteristics and found lower adjusted mortality in transfused patients who had a nadir hemoglobin of 7-8.9 g/dL but no excess mortality in those transfused patients with higher nadir hemoglobin values who were transfused.