Guidelines Add Prasugrel, Favor Quicker Angiography

The American College of Cardiolo­gy Foundation and the American Heart Association have published updated guidelines for managing pa­tients with unstable angina/non–ST el­evation myocardial infarction, taking into consideration the use of a newer agent, prasugrel, as an alternative to clopidogrel, and recommending diag­nostic angiography sooner for patients at high risk, among other changes.

The guidelines, published March 28in the Journal of the American College of Cardiology  (Am. J. Cardiol. 2011 March 28 [doi:10.1016/j.jacc.2011.02.009]) and based on the most recent clinical trial ev­idence available, update recommenda­tions from 2007, and include several changes clinicians should be aware of, the guidelines’ lead author, Dr. R. Scott Wright of the Mayo Clinic in Rochester, Minn., said in an e-mail interview. These are, in order of importance:

• The timing of invasive therapy in medium- and high-risk patients.
• The role of triple- vs. dual-antiplatelet therapy in patients at medium and high risk.
• The role of invasive therapy in pa­tients with chronic kidney disease.
• The importance of participating in quality improvement processes.
• The role of prasugrel in non–ST ele­vation acute coronary syndrome.

Clinicians face tough decisions about when to perform an invasive strategy such as diagnostic coronary angiography – whether within hours of presentation or days, Dr. Wright and his colleagues wrote in their analysis.

Immediate catheterization with revas­cularization of unstable coronary lesions may prevent ischemic events that would otherwise occur during medical therapy – but pretreatment with antithrombotics “may diminish thrombus burden and ‘passivate’ unstable plaques,” improving the safety of the procedure and reducing the risk of ischemic complications.

<[stk 2]>The new guidelines, based on findings from three randomized controlled trials evaluating the timing of angiography, recommend an early invasive strategy (12-24 hours after presentation) over a delayed invasive strategy (more than 24 hours after presentation) for initially stabilized high-risk patients with UA/NSTEMI. <[etk]>

“For patients not at high risk, a delayed invasive approach is also reasonable,” Dr. Wright and his colleagues wrote.

Several changes to earlier recommen­dations for antiplatelet therapy are con­tained in the new guidelines, including altered loading doses for clopidogrel to counter the potential for the drug to be less effective in some patient groups, and the addition of prasugrel, which was approved by the Food and Drug Ad­ministration after the last guidelines were published.

Prasugrel, in a randomized controlled trial comparing it with clopidogrel, was shown to be superior in reducing clinical events but at the expense of an increased risk of bleeding, the guideline writers noted.

In March 2010 the FDA issued a warn­ing that in some patient groups clopido­grel is less effective than it should be because of a genetic variant that inhibits the body’s conversion of the prodrug to the drug.

However, Dr. Wright and his col­leagues stopped short of endorsing pra­sugrel as a first choice over clopidogrel because of the higher bleeding risk and other considerations. People aged 75 years or older, those with a history of transient ischemic attack or stroke or with active pathological bleeding, and people weighing less than 60 kg saw no benefit and/or net harm from prasugrel, they noted.

Dr. Wright and his colleagues also changed recommendations involving glycoprotein IIB/IIIa inhibitors, noting that recent studies “more strongly sup­port a strategy of selective rather than provisional use of GP IIb/IIIa inhibitor
therapy as part of triple-antiplatelet ther­apy,” due to concerns about the poten­tial bleeding risks. Therefore, according to the new guidelines, for UA/NSTEMI patients who are at low risk of ischemic events or at high risk of bleeding and who are already receiving aspirin and clopidogrel, upstream GP IIb/IIIa in­hibitors are not recommended.

People with kidney disease should re­ceive adequate preparatory hydration before catheterization, say the new guidelines, which also tweak earlier recommendations about the contrast agents used in angiography.

Finally, the guidelines recommend that clinicians and hospitals “participate in a standardized quality-of-care data registry designed to track and measure outcomes, complications, and adherence to evidence-based processes of care and quality improvement for UA/NSTEMI.” No such recommendation had been included in the 2007 guidelines.

I have checked the following facts in my story: (Please initial each.)

<[stk 1]>Dr. Wright declared no conflicts of in­terest. Several of Dr. Wright’s coau­thors, including Dr. Jeffrey L. Anderson, the writing committee’s vice chair, dis­closed consultant relationships with pharmaceutical firms Sanofi-Aventis, Bristol Myers-Squibb, Lilly, and Daiichi. Members with conflicts were not per­mitted to vote on recommended drug therapies.

The American College of Cardiolo­gy Foundation and the American Heart Association have published updated guidelines for managing pa­tients with unstable angina/non–ST el­evation myocardial infarction, taking into consideration the use of a newer agent, prasugrel, as an alternative to clopidogrel, and recommending diag­nostic angiography sooner for patients at high risk, among other changes.

The guidelines, published March 28in the Journal of the American College of Cardiology  (Am. J. Cardiol. 2011 March 28 [doi:10.1016/j.jacc.2011.02.009]) and based on the most recent clinical trial ev­idence available, update recommenda­tions from 2007, and include several changes clinicians should be aware of, the guidelines’ lead author, Dr. R. Scott Wright of the Mayo Clinic in Rochester, Minn., said in an e-mail interview. These are, in order of importance:

• The timing of invasive therapy in medium- and high-risk patients.
• The role of triple- vs. dual-antiplatelet therapy in patients at medium and high risk.
• The role of invasive therapy in pa­tients with chronic kidney disease.
• The importance of participating in quality improvement processes.
• The role of prasugrel in non–ST ele­vation acute coronary syndrome.

Clinicians face tough decisions about when to perform an invasive strategy such as diagnostic coronary angiography – whether within hours of presentation or days, Dr. Wright and his colleagues wrote in their analysis.

Immediate catheterization with revas­cularization of unstable coronary lesions may prevent ischemic events that would otherwise occur during medical therapy – but pretreatment with antithrombotics “may diminish thrombus burden and ‘passivate’ unstable plaques,” improving the safety of the procedure and reducing the risk of ischemic complications.

<[stk 2]>The new guidelines, based on findings from three randomized controlled trials evaluating the timing of angiography, recommend an early invasive strategy (12-24 hours after presentation) over a delayed invasive strategy (more than 24 hours after presentation) for initially stabilized high-risk patients with UA/NSTEMI. <[etk]>

“For patients not at high risk, a delayed invasive approach is also reasonable,” Dr. Wright and his colleagues wrote.

Several changes to earlier recommen­dations for antiplatelet therapy are con­tained in the new guidelines, including altered loading doses for clopidogrel to counter the potential for the drug to be less effective in some patient groups, and the addition of prasugrel, which was approved by the Food and Drug Ad­ministration after the last guidelines were published.

Prasugrel, in a randomized controlled trial comparing it with clopidogrel, was shown to be superior in reducing clinical events but at the expense of an increased risk of bleeding, the guideline writers noted.

In March 2010 the FDA issued a warn­ing that in some patient groups clopido­grel is less effective than it should be because of a genetic variant that inhibits the body’s conversion of the prodrug to the drug.

However, Dr. Wright and his col­leagues stopped short of endorsing pra­sugrel as a first choice over clopidogrel because of the higher bleeding risk and other considerations. People aged 75 years or older, those with a history of transient ischemic attack or stroke or with active pathological bleeding, and people weighing less than 60 kg saw no benefit and/or net harm from prasugrel, they noted.

Dr. Wright and his colleagues also changed recommendations involving glycoprotein IIB/IIIa inhibitors, noting that recent studies “more strongly sup­port a strategy of selective rather than provisional use of GP IIb/IIIa inhibitor
therapy as part of triple-antiplatelet ther­apy,” due to concerns about the poten­tial bleeding risks. Therefore, according to the new guidelines, for UA/NSTEMI patients who are at low risk of ischemic events or at high risk of bleeding and who are already receiving aspirin and clopidogrel, upstream GP IIb/IIIa in­hibitors are not recommended.

People with kidney disease should re­ceive adequate preparatory hydration before catheterization, say the new guidelines, which also tweak earlier recommendations about the contrast agents used in angiography.

Finally, the guidelines recommend that clinicians and hospitals “participate in a standardized quality-of-care data registry designed to track and measure outcomes, complications, and adherence to evidence-based processes of care and quality improvement for UA/NSTEMI.” No such recommendation had been included in the 2007 guidelines.

I have checked the following facts in my story: (Please initial each.)

<[stk 1]>Dr. Wright declared no conflicts of in­terest. Several of Dr. Wright’s coau­thors, including Dr. Jeffrey L. Anderson, the writing committee’s vice chair, dis­closed consultant relationships with pharmaceutical firms Sanofi-Aventis, Bristol Myers-Squibb, Lilly, and Daiichi. Members with conflicts were not per­mitted to vote on recommended drug therapies.

The American College of Cardiolo­gy Foundation and the American Heart Association have published updated guidelines for managing pa­tients with unstable angina/non–ST el­evation myocardial infarction, taking into consideration the use of a newer agent, prasugrel, as an alternative to clopidogrel, and recommending diag­nostic angiography sooner for patients at high risk, among other changes.

The guidelines, published March 28in the Journal of the American College of Cardiology  (Am. J. Cardiol. 2011 March 28 [doi:10.1016/j.jacc.2011.02.009]) and based on the most recent clinical trial ev­idence available, update recommenda­tions from 2007, and include several changes clinicians should be aware of, the guidelines’ lead author, Dr. R. Scott Wright of the Mayo Clinic in Rochester, Minn., said in an e-mail interview. These are, in order of importance:

• The timing of invasive therapy in medium- and high-risk patients.
• The role of triple- vs. dual-antiplatelet therapy in patients at medium and high risk.
• The role of invasive therapy in pa­tients with chronic kidney disease.
• The importance of participating in quality improvement processes.
• The role of prasugrel in non–ST ele­vation acute coronary syndrome.

Clinicians face tough decisions about when to perform an invasive strategy such as diagnostic coronary angiography – whether within hours of presentation or days, Dr. Wright and his colleagues wrote in their analysis.

Immediate catheterization with revas­cularization of unstable coronary lesions may prevent ischemic events that would otherwise occur during medical therapy – but pretreatment with antithrombotics “may diminish thrombus burden and ‘passivate’ unstable plaques,” improving the safety of the procedure and reducing the risk of ischemic complications.

<[stk 2]>The new guidelines, based on findings from three randomized controlled trials evaluating the timing of angiography, recommend an early invasive strategy (12-24 hours after presentation) over a delayed invasive strategy (more than 24 hours after presentation) for initially stabilized high-risk patients with UA/NSTEMI. <[etk]>

“For patients not at high risk, a delayed invasive approach is also reasonable,” Dr. Wright and his colleagues wrote.

Several changes to earlier recommen­dations for antiplatelet therapy are con­tained in the new guidelines, including altered loading doses for clopidogrel to counter the potential for the drug to be less effective in some patient groups, and the addition of prasugrel, which was approved by the Food and Drug Ad­ministration after the last guidelines were published.

Prasugrel, in a randomized controlled trial comparing it with clopidogrel, was shown to be superior in reducing clinical events but at the expense of an increased risk of bleeding, the guideline writers noted.

In March 2010 the FDA issued a warn­ing that in some patient groups clopido­grel is less effective than it should be because of a genetic variant that inhibits the body’s conversion of the prodrug to the drug.

However, Dr. Wright and his col­leagues stopped short of endorsing pra­sugrel as a first choice over clopidogrel because of the higher bleeding risk and other considerations. People aged 75 years or older, those with a history of transient ischemic attack or stroke or with active pathological bleeding, and people weighing less than 60 kg saw no benefit and/or net harm from prasugrel, they noted.

Dr. Wright and his colleagues also changed recommendations involving glycoprotein IIB/IIIa inhibitors, noting that recent studies “more strongly sup­port a strategy of selective rather than provisional use of GP IIb/IIIa inhibitor
therapy as part of triple-antiplatelet ther­apy,” due to concerns about the poten­tial bleeding risks. Therefore, according to the new guidelines, for UA/NSTEMI patients who are at low risk of ischemic events or at high risk of bleeding and who are already receiving aspirin and clopidogrel, upstream GP IIb/IIIa in­hibitors are not recommended.

People with kidney disease should re­ceive adequate preparatory hydration before catheterization, say the new guidelines, which also tweak earlier recommendations about the contrast agents used in angiography.

Finally, the guidelines recommend that clinicians and hospitals “participate in a standardized quality-of-care data registry designed to track and measure outcomes, complications, and adherence to evidence-based processes of care and quality improvement for UA/NSTEMI.” No such recommendation had been included in the 2007 guidelines.

I have checked the following facts in my story: (Please initial each.)

<[stk 1]>Dr. Wright declared no conflicts of in­terest. Several of Dr. Wright’s coau­thors, including Dr. Jeffrey L. Anderson, the writing committee’s vice chair, dis­closed consultant relationships with pharmaceutical firms Sanofi-Aventis, Bristol Myers-Squibb, Lilly, and Daiichi. Members with conflicts were not per­mitted to vote on recommended drug therapies.