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AHA/ACC guideline: Ticagrelor preferred over Clopidogrel in NSTE-ACS patients with early invasive or ischemia-guided strategy or receiving a coronary stent


American Heart Association ( AHA ) and American College of Cardiology ( ACC ) have updated the guideline for the management of patients with non–ST-elevation acute coronary syndromes ( NSTE-ACS ).
The guideline supports differentiation among currently available P2Y12 inhibitors, including Ticagrelor ( Brilinta; in Europe: Brilique ), Clopidogrel ( Plavix ), and Prasugrel ( Effient; in Europe: Efient ), for these patients.
Ticagrelor is now preferred over Clopidogrel for the management of NSTE-ACS patients who undergo an early invasive ( angiography with intent for PCI if appropriate ) or ischemia-guided strategy ( i.e., medically managed ), or those who receive a coronary stent.

This new guideline is based on a review of multiple clinical trials, including PLATO. There are no clinical outcome trials that compare Prasugrel and Ticagrelor.

Ticagrelor is indicated to reduce the rate of thrombotic cardiovascular events in patients with ACS ( unstable angina [ UA ], non–ST-elevation myocardial infarction [ NSTEMI ], or ST-elevation myocardial infarction [ STEMI ] ).
Ticagrelor has been shown to reduce the rate of a combined end point of cardiovascular death, myocardial infarction, or stroke compared to Clopidogrel. The difference between treatments was driven by cardiovascular death and myocardial infarction with no difference in stroke.
In patients treated with percutaneous coronary intervention ( PCI ), it also reduces the rate of stent thrombosis. Ticagrelor has been studied in ACS in combination with Acetylsalicylic acid ( Aspirin ).
Maintenance doses of aspirin more than 100 mg decreased the effectiveness of Ticagrelor.

Brilinta has two Boxed Warnings, one for bleeding risk and the other for Aspirin dose and reduced Brilinta effectiveness. The Boxed Warning on Bleeding Risk states, like other antiplatelet agents, Brilinta can cause significant, sometimes fatal, bleeding. For Aspirin Dose and Brilinta Effectiveness, maintenance doses of Aspirin above 100 mg reduce the effectiveness of Brilinta and should be avoided. After any initial dose, use with Aspirin 75 mg-100 mg per day.

Following are recommendations within the updated AHA/ACC NSTE-ACS guideline specific to oral P2Y12 inhibitors only.

Initial oral antiplatelet therapy in patients with definite or likely NSTE-ACS treated with an initial invasive or ischemia-guided strategy

Class I - A P2Y12 inhibitor ( either Clopidogrel or Ticagrelor ) in addition to Aspirin should be administered for up to 12 months to all patients with NSTE-ACS without contraindications who are treated with either an early invasive or ischemia-guided strategy. Options include: Clopidogrel: 300-mg or 600-mg loading dose, then 75 mg daily ( Level of Evidence [ LOE ]: B ); Ticagrelor: 180-mg loading dose, then 90 mg twice daily ( LOE: B )

Class IIa - It is reasonable to use Ticagrelor in preference to Clopidogrel for P2Y12 treatment in patients with NSTE-ACS who undergo an early invasive or ischemia-guided strategy ( LOE: B )

PCI - Oral antiplatelet agents

Class I - A loading dose of a P2Y12 receptor inhibitor should be given before the procedure in patients undergoing PCI with stenting. ( LOE: A ) Options include: Clopidogrel: 600 mg ( LOE: B ) or Prasugrel: 60 mg ( LOE: B ) or Ticagrelor: 180 mg ( LOE: B ).

In patients receiving a stent ( bare-metal stent or drug-eluting stent [ DES ] ) during PCI for NSTE-ACS, P2Y12 inhibitor therapy should be given for at least 12 months. Options include: Clopidogrel: 75 mg daily ( LOE: B ) or Prasugrel: 10 mg daily ( LOE: B ) or Ticagrelor: 90 mg twice daily ( LOE: B )

Class IIa - It is reasonable to choose Ticagrelor over Clopidogrel for P2Y12 inhibition treatment in patients with NSTE-ACS treated with an early invasive strategy and/or coronary stenting ( LOE: B ).

It is reasonable to choose Prasugrel over Clopidogrel for P2Y12 treatment in patients with NSTE-ACS who undergo PCI who are not at high risk of bleeding complications ( LOE: B ).

If the risk of morbidity from bleeding outweighs the anticipated benefit of a recommended duration of P2Y12 inhibitor therapy after stent implantation, earlier discontinuation ( e.g., less than 12 months ) of P2Y12 inhibitor therapy is reasonable ( LOE: C ).

Class III: Harm - Prasugrel should not be administered to patients with a prior history of stroke or transient ischemic attack ( LOE: B ).

Late hospital and posthospital oral antiplatelet therapy

Class I - Aspirin should be continued indefinitely. The maintenance dose should be 81 mg daily in patients treated with Ticagrelor and 81 mg to 325 mg daily in all other patients ( LOE: A ).

In addition to Aspirin, a P2Y12 inhibitor ( either Clopidogrel or Ticagrelor ) should be continued for up to 12 months in all patients with NSTE-ACS without contraindications who are treated with an ischemia-guided strategy. Options include: Clopidogrel: 75 mg daily ( LOE: B ) or Ticagrelor: 90 mg twice daily ( LOE: B ).

In patients receiving a stent ( bare-metal stent or DES ) during PCI for NSTE-ACS, P2Y12 inhibitor therapy should be given for at least 12 months. Options include: Clopidogrel: 75 mg daily ( LOE: B ) or Prasugrel: 10 mg daily ( LOE: B ) or Ticagrelor: 90 mg twice daily ( LOE: B ).

Class IIa - It is reasonable to choose Ticagrelor over Clopidogrel for maintenance P2Y12 treatment in patients with NSTE-ACS treated with an early invasive strategy and/or PCI ( LOE: B ).

It is reasonable to choose Prasugrel over Clopidogrel for maintenance P2Y12 treatment in patients with NSTE-ACS who undergo PCI who are not at high risk for bleeding complications ( LOE: B ).

If the risk of morbidity from bleeding outweighs the anticipated benefit of a recommended duration of P2Y12 inhibitor therapy after stent implantation, earlier discontinuation ( e.g., less than 12 months ) of P2Y12 inhibitor therapy is reasonable ( LOE: C ), ( Xagena )

Source: AstraZeneca, 2014

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