2016 ACC/AHA Guideline Focused Update on Duration of Dual Antiplatelet Therapy1

BRILINTA PREFERRED OVER CLOPIDOGREL IN ACUTE CORONARY SYNDROME (ACS)

First time in patients with ST-elevation myocardial infarction (STEMI) who have received a coronary stent (Class IIa; LOE B-R)

In patients with non–ST-elevation ACS (NSTE-ACS) who have received a coronary stent or are managed with medical therapy alone (Class IIa; LOE B-R)

Class I recommendation for BRILINTA as a treatment option in patients with ACS who undergo stent implantation or who are managed with medical therapy alone (LOE B-R)

Select recommendations on duration of dual antiplatelet therapy (DAPT)1

BRILINTA is indicated to reduce the rate of cardiovascular death, myocardial infarction (MI), and stroke in patients with acute coronary syndrome (ACS) or a history of myocardial infarction.

For at least the first 12 months following ACS, it is superior to clopidogrel.2

BRILINTA also reduces the rate of stent thrombosis in patients who have been stented for treatment of ACS.2

Following are recommendations within the 2016 ACC/AHA guideline focused update on duration of DAPT specific to oral P2Y12 inhibitors only. The updated guideline supports differentiation among currently available P2Y12 inhibitors for:

DAPT in patients with ACS treated with PCI1

RECOMMENDATION

COR

LOE

In patients with ACS (NSTE-ACS or STEMI) treated with DAPT after BMS or DES implantation, P2Y12 inhibitor therapy (clopidogrel, prasugrel, or ticagrelor) should be given for at least 12 months

I

B-R

In patients treated with DAPT, a daily aspirin dose of 81 mg (range, 75 mg to 100 mg) is recommended.

I

B-NR

In patients with ACS (NSTE-ACS or STEMI) treated with DAPT after coronary stent implantation, it is reasonable to use ticagrelor in preference to clopidogrel for maintenance P2Y12 inhibitor therapy

IIa

B-R

In patients with ACS (NSTE-ACS or STEMI) treated with DAPT after coronary stent implantation who are not at high risk for bleeding complications and who do not have a history of stroke or TIA, it is reasonable to choose prasugrel over clopidogrel for maintenance P2Y12 inhibitor therapy

IIa

B-R

In patients with ACS (NSTE-ACS or STEMI) treated with coronary stent implantation who have tolerated DAPT without a bleeding complication and who are not at high bleeding risk (eg, prior bleeding on DAPT, coagulopathy, oral anticoagulant use), continuation of DAPT (clopidogrel, prasugrel, or ticagrelor) for longer than 12 months may be reasonable

IIb

ASR

In patients with ACS treated with DAPT after DES implantation who develop a high risk of bleeding (eg, treatment with oral anticoagulant therapy), are at high risk of severe bleeding complication (eg, major intracranial surgery), or develop significant overt bleeding, discontinuation of P2Y12 inhibitor therapy after 6 months may be reasonable

IIb

C-LD

Prasugrel should not be administered to patients with a prior history of stroke or TIA

III: Harm

B-R

DAPT in patients with ACS treated with medical therapy alone
(without revascularization or fibrinolytic therapy)1

RECOMMENDATION

COR

LOE

In patients with ACS who are managed with medical therapy alone (without revascularization or fibrinolytic therapy) and treated with DAPT, P2Y12 inhibitor therapy (clopidogrel or ticagrelor) should be continued for at least 12 months

I

B-R

In patients treated with DAPT, a daily aspirin dose of 81 mg (range, 75 mg to 100 mg) is recommended

I

B-NR

In patients with NSTE-ACS who are managed with medical therapy alone (without revascularization or fibrinolytic therapy) and treated with DAPT, it is reasonable to use ticagrelor in preference to clopidogrel for maintenance P2Y12 inhibitor therapy

IIa

B-R

In patients with ACS treated with medical therapy alone (without revascularization or fibrinolytic therapy) who have tolerated DAPT without bleeding complication and who are not at high bleeding risk (eg, prior bleeding on DAPT, coagulopathy, oral anticoagulant use), continuation of DAPT for longer than 12 months may be reasonable

IIb

ASR

CLASS OF RECOMMENDATION (COR)

Class I Recommends that the procedure/treatment should be performed/administered
Class IIa Is reasonable to perform procedure/administer treatment
Class IIb Recommends that the procedure treatment may be considered
Class III (Harm) State that the treatment is harmful to patients

LEVELS OF EVIDENCE (LOE)

Level A High-quality evidence from more than 1 RCT, meta-analysis of high-quality RCTs, or one or more RCTs collaborated by high-quality registry studies
Level B-R Moderate-quality evidence from 1 or more RCTs or meta-analyses of moderate-quality RCTs
Level B-NR Moderate-quality evidence from 1 or more well-designed, well-executed nonrandomized studies, observational studies, or registry studies, and meta-analysis of such studies
Level C-LD Randomized or nonrandomized observational or registry studies with limitations of design or execution, meta-analysis of such studies, or physiological or mechanistic studies in human studies

ACC=American College of Cardiology; AHA=American Heart Association; BMS=bare-metal stent; COR=class of recommendation; DAPT=dual antiplatelet therapy; DES=drug-eluting stent; LOE=level of evidence; NSTE-ACS=non–ST-elevation ACS; PCI=percutaneous coronary intervention; RCT=randomized controlled trial; SR=systematic review; STEMI=ST-elevation MI; TIA=transient ischemic attack.

IMPORTANT SAFETY INFORMATION FOR BRILINTA® (ticagrelor) 60-mg AND 90-mg TABLETS
WARNING: (A) BLEEDING RISK, (B) ASPIRIN DOSE AND BRILINTA EFFECTIVENESS

A. BLEEDING RISK
  • BRILINTA, like other antiplatelet agents, can cause significant, sometimes fatal bleeding
  • Do not use BRILINTA in patients with active pathological bleeding or a history of intracranial hemorrhage
  • Do not start BRILINTA in patients undergoing urgent coronary artery bypass graft surgery
1975408-3218312 Last Updated 10/16

IMPORTANT SAFETY INFORMATION FOR BRILINTA® (ticagrelor) 60-mg AND 90-mg TABLETS

WARNING: (A) BLEEDING RISK, (B) ASPIRIN DOSE AND BRILINTA EFFECTIVENESS A. BLEEDING RISK

  • BRILINTA, like other antiplatelet agents, can cause significant, sometimes fatal bleeding
  • Do not use BRILINTA in patients with active pathological bleeding or a history of intracranial hemorrhage
  • Do not start BRILINTA in patients undergoing urgent coronary artery bypass graft surgery 
  • If possible, manage bleeding without discontinuing BRILINTA. Stopping BRILINTA increases the risk of subsequent cardiovascular events

B. ASPIRIN DOSE AND BRILINTA EFFECTIVENESS

  • Maintenance doses of aspirin above 100 mg reduce the effectiveness of BRILINTA and should be avoided

CONTRAINDICATIONS

  • BRILINTA is contraindicated in patients with a history of intracranial hemorrhage or active pathological bleeding such as peptic ulcer or intracranial hemorrhage. BRILINTA is also contraindicated in patients with hypersensitivity (eg, angioedema) to ticagrelor or any component of the product

WARNINGS AND PRECAUTIONS

  • Dyspnea was reported in about 14% of patients treated with BRILINTA, more frequently than in patients treated with control agents. Dyspnea resulting from BRILINTA is often self-limiting
  • Discontinuation of BRILINTA will increase the risk of MI, stroke, and death. When possible, interrupt therapy with BRILINTA for 5 days prior to surgery that has a major risk of bleeding. If BRILINTA must be temporarily discontinued, restart as soon as possible
  • Ticagrelor can cause ventricular pauses. Bradyarrhythmias including AV block have been reported in the post-marketing setting. PLATO and PEGASUS excluded patients at increased risk of bradyarrhythmias not protected by a pacemaker, and they may be at increased risk of developing bradyarrhythmias with ticagrelor
  • Avoid use of BRILINTA in patients with severe hepatic impairment. Severe hepatic impairment is likely to increase serum concentration of ticagrelor and there are no studies of BRILINTA in these patients

ADVERSE REACTIONS

  • The most common adverse reactions associated with the use of BRILINTA included bleeding and dyspnea: In PLATO, for BRILINTA vs clopidogrel, non-CABG PLATO-defined major bleeding (3.9% vs 3.3%) and dyspnea (14% vs 8%); in PEGASUS, BRILINTA vs aspirin alone, TIMI Total Major bleeding (1.7% vs 0.8%) and dyspnea (14% vs 6%)

DRUG INTERACTIONS

  • Avoid use with strong CYP3A inhibitors and strong CYP3A inducers. BRILINTA is metabolized by CYP3A4/5. Strong inhibitors substantially increase ticagrelor exposure and so increase the risk of adverse events. Strong inducers substantially reduce ticagrelor exposure and so decrease the efficacy of ticagrelor
  • Patients receiving more than 40 mg per day of simvastatin or lovastatin may be at increased risk of statin-related adverse events
  • Monitor digoxin levels with initiation of, or change in, BRILINTA therapy

INDICATIONS

BRILINTA is indicated to reduce the rate of cardiovascular death, myocardial infarction (MI), and stroke in patients with acute coronary syndrome (ACS) or a history of myocardial infarction. For at least the first 12 months following ACS, it is superior to clopidogrel.

BRILINTA also reduces the rate of stent thrombosis in patients who have been stented for treatment of ACS.

DOSING

In the management of ACS, initiate BRILINTA treatment with a 180-mg loading dose. Administer 90 mg twice daily during the first year after an ACS event. After one year administer 60 mg twice daily. Use BRILINTA with a daily maintenance dose of aspirin of 75-100 mg.

Please read full Prescribing Information , including Boxed WARNINGS, and Medication Guide  .

REFERENCES:

  1. Levine GN, Bates ER, Bittl JA, et al. 2016 ACC/AHA Guideline Focused Update on Duration of Dual Antiplatelet Therapy in Patients With Coronary Artery Disease. Circulation. 2016;134:e123–e155.
  2. BRILINTA [package insert]. Wilmington, DE: AstraZeneca; 2016.

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