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

For women presenting with an acute coronary syndrome, what is the comparative effectiveness of the newer and more potent anti-platelet agents vs. older and less potent anti-platelet agents.

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:

New agent: Irreversible P2Y12 receptor blocker Prasugrel v. Clopidogrel

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.)

Female patients with Acute Corornary syndromes presenting to hospital, with early invasive therapy (going to cardiac cath lab), either undergoing percutaneous coronary revascularization, CABG, or medical therapy.

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

Using already established bleeding risk scores to evaluate outcomes according to bleeding complications.

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

Female patients are under-represented in most trials, and these new agents with increased potency may have a detrimental risk of bleeding in this group of patients.

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

The only harm is bleeding complication, which we would measure very carefully in all patients and measure prospectively. These are already approved agents and the saftey of either agent has not been proven in the female population.

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

AHRQ Priority Populations

• Women

Federal Health Care Program

• Medicaid
• Medicare

Importance

Describe why this topic is important.

Heart disease is the number one killer of all women in the united states. It is estimated that 500,000 women die each year from heart disease and the incidence and mortality from heart disease is increasing in women each year. There has been tremendous improvements in treatment of patients with heart disease and improvement of mortality especially in patients presenting with Acute coronary Syndromes (ACS)including acute myocardial infarction. Antiplatelet agents (ASA + Thienopyridines) have been the mainstay of therapy for patients with ACS. The current guidelines recommend chronic use of this agents up to one year after presentation with ACS. The safety and efficacy of these agents have been documented by large multicenter clinical trials which proved both safety and efficacy. However, all trials included a small minority of women. None were powered to examine the important safety and efficacy endpoints in women.

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.)

Newer and more potent agents have now become available. While these agents are more effective in reducing platelet reactivity(which is important in ACS), they are associated with higher bleeding complications. Bleeding is especially increased in the female population. Therefore it is unclear whether these agents are safe or effective in this sub-group. Now there have been post-hoc sub group analsyis in the female population, but this is fraught with statistical issues and non accurate information.

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:

It is unclear whether women benefit from these newer agents and whether the increased risk of bleeding is worth the reduction of ischemic events. Major bleeding is associated with higher early and late mortality and therefore this becomes a very important issue in the female population.

Potential Impact

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

Clinicians/ societies (who write guidelines) will be finally informed on safety and efficacy profile of these newer agents compared to older standard therapy.

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

In the next two years.

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

This question applies to the female population who are notoriously under-represented in all clinical trials in cardiovascular disease.

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)

Clinicians/ societies (who write guidelines) will be finally informed on safety and efficacy profile of these newer agents compared to older standard therapy.

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

Research