Briefly describe a specific question, or set of related questions, about a health care test or treatment that this program should consider.

Unstable Angina (UA)/Non–ST-Elevation Myocardial Infarction (NSTEMI)

1. Is there an overall positive benefit to risk ratio for triple antithrombotic therapy (aspirin, clopidogrel, warfarin) in post-ACS patients with an indication for warfarin (e.g., atrial fibrillation)? 2) Added to aspirin, is there a difference in outcomes (ischemic events, bleeding risks with intervention) between a short-acting GP IIb/IIIa inhibitor and clopidogrel as the second choice for upstream therapy (with clopidogrel being added at catheterization in PCI patients for upstream GPI patients, and selective application of GPI in upstream clopidogrel patients).

2. Which ADP receptor antagonist agent provides the best overall benefit/risk/cost-effectiveness outcomes for initial (in-hospital) and longer-term (outpatient) antiplatelet therapy: clopidogrel, prasugrel, ticagrelor? For age >75y? For diabetics?

3. Is earlier (<48h) or later (>=5 days) CABG preferred for UA/NSTEMI patients triaged to surgical intervention at early coronary angiography? 5) What is the optimal time-window for coronary angiography with intended PCI in UA/NSTEMI patients at higher risk (GRACE score >140) and lower risk (i.e., 4-12 h, 12-24 h, 48-96 h)? 6) What is the optimal initial dose (after loading) of aspirin (i.e., 81 vs. 325 mg/d) for patients undergoing PCI with stenting and treated with variously potent antiplatelet agents, i.e., clopidogrel? Prasugrel? Ticagrelor? 7) Is there an advantage to early (on admission), high dose statin loading over post- catheterization, evening, or next day/pre-discharge statin therapy initiation on outcomes? 8) Is long-term beta-blocker therapy effective in post-UA/NSTEMI pts with complete revascularization and normal ejection fraction (>50%)? 9) Does the incorporation of routine pre-discharge or early post-discharge platelet function testing (e.g., with VerifyNow) and titration to optimal antiplatelet effect (e.g., 100-200PFUs) using various doses of clopidogrel and/or

Does your question include a comparison of different health care approaches? (If no, your topic will still be considered.)

yes

If yes, explain the specific technologies, devices, drugs, or interventions you would like to see compared:

For question #3: compare available ADP receptor antagonists to determine best overall benefit/risk/cost-effectiveness outcomes for initial (in-hospital) and longer-term (outpatient) anti-platelet therapy For question #4: compare influence of timing on outcomes of CABG for UA/NSTEMI patients triaged to surgical intervention For question #7: compare early vs. delayed initiation of statin therapy on outcomes For question #10: compare fondaparinux to enoxaparin to determine optimal initial conservative approach

What patients or group(s) of patients does your question apply to? (Please include specific details such as age range, gender, coexisting diagnoses, and indications for therapy.)

Co-morbid/multi-morbid patients with UA/NSTEMI

Are there subgroups of patients that your question might apply to? (For example, an ethnic group, stage or severity of a disease.)

Minorities, Women

Describe the health-related benefits you are interested in. (For example, improvements in patient symptoms or problems from treatment or diagnosis.)

Improvements in mortality and morbidity and quality of life for patients with UA/NSTEMI

Describe any health-related risks, side effects, or harms that you are concerned about.

Bleeding risks associated with anti-platelet and anticoagulant therapy in patients with UA/NSTEMI and co-morbid disease

Appropriateness for EHC Program

Does your question include a health care drug, intervention, device, or technology available (or likely to be available) in the U.S.?

yes

Which priority area(s) and population(s) does this topic apply to? (check all that apply)

EHC Priority Conditions (updated in 2008)

• Cardiovascular disease, including stroke and hypertension
• Diabetes mellitus

AHRQ Priority Populations

• Minority groups
• Women
• Elderly
• Individuals with special health care needs, including individuals with disabilities or who need chronic care or end-of-life health care

Federal Health Care Program

None

Importance

Describe why this topic is important.

UA/NSTEMI constitutes a clinical syndrome subset of the acute coronary syndromes (ACS) that is usually, but not always, caused by atherosclerotic coronary artery disease and is associated with an increased risk of cardiac death and subsequent myocardial infarction (MI). In the spectrum of ACS, UA/NSTEMI is defined by electrocardiographic ST-segment depression or prominent T-wave inversion and/or positive biomarkers of necrosis (e.g., troponin) in the absence of ST-segment elevation and in an appropriate clinical setting (chest discomfort or angina equivalent).

It is estimated that in 2006, there were 1,365,000 unique hospitalizations (hospital discharges) for patients with ACS (including STEMI); 765,000 were male and 6000,000 were female. Moreover, it has been reported that changes in practice for both pharmacologic and interventional treatments have been accompanied by significant decreases in the rates of in-hospital death, cardiogenic shock, and new MI among patients with NSTEMI.

What specifically motivated you to ask this question? (For example, you are developing a clinical guideline, working with a policy with large uncertainty about the appropriate approach, costly intervention, new research you have read, items in the media you may have seen, a clinical practice dilemma you know of, etc.)

A clinical practice guideline is being updated and a full guideline revision is being planned.

Does your question represent uncertainty for clinicians and/or policy-makers? (For example, variations in clinical care, controversy in what constitutes appropriate clinical care, or a policy decision.)

yes

If yes, please explain:

The comparative effectiveness of both specific pharmacologic and revascularization strategies for patients with UA/NSTEMI is uncertain.

Potential Impact

How will an answer to your research question be used or help inform decisions for you or your group?

Evidence gathered, collated, and reviewed will inform clinical practice guideline recommendations.

Describe the timeframe in which an answer to your question is needed.

6-8 months

Describe any health disparities, inequities, or impact on vulnerable populations your question applies to.

Nominator Information

Other Information About You: (optional)

Please choose a description that best describes your role or perspective: (you may select more than one category if appropriate)

Evidence gathered, collated, and reviewed will inform clinical practice guideline recommendations.

Are you making a suggestion as an individual or on behalf of an organization?

Organization

Please tell us how you heard about the Effective Health Care Program