ACS: BRILINTA VS CLOPIDOGREL CLINICAL DATA

SUPERIOR TO CLOPIDOGREL : 18,000 PATIENTS PROVE IT

BRILINTA HAS BEEN PROVEN SUPERIOR TO CLOPIDOGREL IN REDUCING THROMBOTIC CV EVENTS AT 12 MONTHS IN PATIENTS WITH 1,2

CURVES SEPERATED BY 30 DAYS AND CONTINUES TO DIVERGE THROUGHOUT THE 12-MONTH TREATMENT PERIOD1,2

IN PATIENTS WITH ACS IN PLATO

MORE PATIENTS TAKING CLOPIDOGREL SUFFERED HEART ATTACKS AT 12 MONTHS THAN THOSE TAKING BRILINTA 1

BRILINTA HELPED PROTECT MORE PATIENTS THAN CLOPIDOGREL FROM SUFFFERING ANOTHER HEART ATTACK2

THROMBOTIC CV EVENTS IN THE FINAL DIAGNOSIS SUBGROUP2

BRILINTA 90 mg plus aspirin was studied vs clopidogrel plus aspirin in more than 18,000 patients, including STEMI (ST-elevation myocardial infarction), NSTEMI (non–ST-elevation myocardial infarction), and UA (unstable angina) patients, across 43 countries and 862 sites in the PLATO (PLATelet inhibition and patient Outcomes) study.2

Patients were treated for at least 6 months and up to 12 months. Patients were excluded if they had a previous intracranial hemorrhage, had gastrointestinal bleeding within 6 months, had a known bleeding diathesis or coagulation disorder, or required treatment with anticoagulants. BRILINTA and clopidogrel were studied with aspirin and other standard therapies.1

PLATO was designed to mirror real-world clinical practice across ACS diagnoses and medical or invasive treatment approaches.5***

***PLATO included both medical and invasive (PCI or CABG) treatment approaches. Patients who received fibrinolytic therapy within the previous 24 hours or who had a need for chronic oral anticoagulation therapy were excluded.

SUPERIOR TO CLOPIDOGREL: 45,000 PATIENTS CONFIRM IT

Patients studied in a real-world registry confirmed the significant reductions in CV events for BRILINTA vs clopidogrel seen in the PLATO trial 6

  • This was an observational study ina subset of patients enrolled in the swedish web
  • Acute MIpatients enrolled in the SWEDHEART registry were discharged on aspirin
  • Sensitivity analysis conducted at 12 months showed results

COMPARISON OF THE REAL-WORLD REGISTRY WITH THE PLATO CLINICAL TRIAL

SUPERIOR TO CLOPIDOGREL: 18,000 PATIENTS PROVE IT

BRILINTA HAS BEEN PROVEN SUPERIOR TO CLOPIDOGREL IN REDUCING
THROMBOTIC CV EVENTS AT 12 MONTHS IN PATIENTS WITH ACS1,2

PLATO PRIMARY EFFICACY END POINT: COMPOSITE OF CV DEATH, MI,† OR STROKE1,2

†Excluding silent Ml.

  • Primary efficacy end point (composite of CV death, MI,† or stroke) at 12 months for BRILINTA plus aspirin vs clopidogrel plus aspirin: Events per 1000 patient years 111 vs 131, respectively1

‡Hazard ratio derived from a Cox proportional-hazards model on data from the primary and secondary end points.2

PLATO PRIMARY EFFICACY END POINT: COMPOSITE OF CV DEATH, MI,† OR STROKE1,2

BRILINTA has been proven superior to clopidogrel in reducing thrombotic cv events at 12 months in patients with ACS.

†Excluding silent MI.

  • Primary efficacy end point (composite of CV death, MI,† or stroke) at 12 months for BRILINTA plus aspirin vs clopidogrel plus aspirin: Events per 1000 patient years 111 vs 131, respectively1

‡Hazard ratio derived from a Cox proportional-hazards model on data from the primary and secondary end points.2

*PLATO STUDY DESCRIPTION

  • Study treatments: BRILINTA (180-mg loading dose, 90 mg twice daily thereafter) and clopidogrel (300-mg to 600-mg loading dose, 75 mg daily thereafter) in combination with aspirin and other standard therapies
  • Number/Type of patients: 18,624 patients admitted to the hospital with ACS
  • Primary efficacy end point: Composite CV death, MI, and stroke
  • Treatment duration: Patients were treated for at least 6 months and up to 12 months
  • Key exclusion criteria:
    • Previous intracranial hemorrhage
    • Gastrointestinal bleeding within 6 months
    • Known bleeding diathesis or coagulation disorder or required treatment with anticoagulants

*VIEW THE PLATO STUDY DESCRIPTION

*VIEW THE PLATO STUDY DESCRIPTION

CURVES SEPARATED BY 30 DAYS AND CONTINUED TO DIVERGE THROUGHOUT THE 12-MONTH TREATMENT PERIOD1,2

  • PLATO was a randomized, double-blind, controlled comparative study in international ACS patients hospitalized with or without ST-segment elevation, with an onset of symptoms within 24 hours (N=18,624)1,2
  • BRILINTA and clopidogrel were studied with aspirin and other therapies1
  • Study period was 12 months, with a median duration of therapy of 277 days1,2
  • At 30 days, BRILINTA + aspirin reduced the primary composite end point of CV death, MI or stroke by 12% RRR (0.6% ARR) vs clopidogrel + aspirin (4.8% vs 5.4%; HR: 0.88; 95% CI:0.77-1.0)1,2

BLEEDING OUTCOMES FOR BRILINTA COMPARED WITH CLOPIDOGREL IN THE PLATO STUDY1

PLATO-DEFINED NON–CABG-RELATED BLEEDING1

NON–CABG-RELATED BLEEDING RATESa BRILINTA 90 MG + ASPIRIN (N=9235) % (n) PATIENTS WITH EVENT CLOPIDOGREL + ASPIRIN (N=9186) % (n) PATIENTS WITH EVENT
PLATO MAJOR + MINOR 7.7 (713) 6.2 (567)
MAJOR 3.9 (362) 3.3 (306)
FATAL/LIFE-THREATENING 1.9 (171) 1.6 (151)
FATAL 0.2 (15) 0.2 (16)
INTRACRANIAL HEMORRHAGE
(FATAL/LIFE-THREATENING)		 0.3 (26) 0.2 (15)
  • About half of non–CABG-related major bleeding events were in the first 30 days1

PLATO SAFETY END POINTS: PLATO-DEFINED CABG-RELATED BLEEDING1

CABG-related bleeding ratesa BRILINTA 90 mg + aspirin (N=770) n (%) patients with event Clopidogrel + aspirin (N=814) n (%) patients with event
PLATO total major 626 (81.3) 666 (81.8)
Fatal/life-threatening 337 (43.8) 350 (43.0)
Fatal 6 (0.8) 7 (0.9)
  • The PLATO trial did not show an advantage for BRILINTA 90 mg compared with clopidogrel for CABG-related bleeding1
  • Rates of major fatal/life-threatening CABG-related bleeding were similar between BRILINTA 90 mg and clopidogrel when study drug was withheld 1-5 days before CABG surgery1
  • When antiplatelet therapy was stopped 5 days before CABG, major bleeding occurred in 75% of patients receiving BRILINTA 90 mg and in 79% of patients receiving clopidogrel1
    • aPLATO used the following bleeding severity categorization1:
    • PLATO minor bleed: requires medical intervention to stop or treat bleeding
    • PLATO major bleed: any one of the following: fatal; intracranial; intrapericardial with cardiac tamponade; hypovolemic shock or severe hypotension requiring intervention; significantly disabling (eg, intraocular with permanent vision loss); associated with a decrease in Hb of at least 3 g/dL (or a fall in Hct of at least 9%); transfusion of 2 or more units
    • PLATO major bleed, fatal/life-threatening: any major bleed as described above and associated with a decrease in Hb of more than 5 g/dL (or a fall in Hct of at least 15%); transfusion of 4 or more units
    • Fatal: a bleeding event that directly led to death within 7 days

Related links

Review additional safety data from the PLATO trial

See how real-world evidence confirms the PLATO results

View data in patients with a history of MI

IN PATIENTS WITH ACS IN PLATO

MORE PATIENTS TAKING CLOPIDOGREL SUFFERED HEART ATTACKS
AT 12 MONTHS THAN THOSE TAKING BRILINTA1

PLATO SECONDARY EFFICACY END POINT: MI AT 12 MONTHS1,2§//¶

§K-M rate is the rate of first events only.

//Excluding silent MI.

Including patients who could have had other nonfatal events or died.

#NNT was 91; NNT=1/ARR; ARR=6.9%?5.8%=1.1%; NNT=1/0.011=90.9.

  • Secondary efficacy end point of MI at 12 months for BRILINTA plus aspirin vs clopidogrel plus aspirin: Events per 1000 patient years 65 vs 76, respectively1

**Hazard ratio derived from a Cox proportional-hazards model on data from the primary and secondary end points.2

PLATO SECONDARY EFFICACY END POINT: MI AT 12 MONTHS1,2§//¶

BRILINTA helped protect more patients than clopidogrel from suffering another heart attack.

§K-M rate is the rate of first events only.

//Excluding silent MI.

Including patients who could have had other nonfatal events or died.

#NNT was 91; NNT=1/ARR; ARR=6.9%–5.8%=1.1%; NNT=1/0.011=90.9.

  • Secondary efficacy end point of MI at 12 months for BRILINTA plus aspirin vs clopidogrel plus aspirin: Events per 1000 patient years 65 vs 76, respectively1

**Hazard ratio derived from a Cox proportional-hazards model on data from the primary and secondary end points.2

*PLATO STUDY DESCRIPTION

  • Study treatments: BRILINTA (180-mg loading dose, 90 mg twice daily thereafter) and clopidogrel (300-mg to 600-mg loading dose, 75 mg daily thereafter) in combination with aspirin and other standard therapies
  • Number/Type of patients: 18,624 patients admitted to the hospital with ACS
  • Primary efficacy end point: Composite CV death, MI, and stroke
  • Treatment duration: Patients were treated for at least 6 months and up to 12 months
  • Key exclusion criteria:
    • Previous intracranial hemorrhage
    • Gastrointestinal bleeding within 6 months
    • Known bleeding diathesis or coagulation disorder or required treatment with anticoagulants

*VIEW THE PLATO STUDY DESCRIPTION

*VIEW THE PLATO STUDY DESCRIPTION

BRILINTA HELPED PROTECT MORE PATIENTS THAN CLOPIDOGREL FROM SUFFERING ANOTHER HEART ATTACK2

IN PATIENTS WITH ACS IN PLATO

CLOPIDOGREL RESULTED IN A 27% HIGHER RISK OF DYING FROM A CV EVENT AT 12 MONTHS VS THOSE TAKING BRILINTA3

PLATO SECONDARY EFFICACY END POINT: CV DEATH AT 12 MONTHS1,2§

§K-M rate is the rate of first events only.

//Excluding silent MI.

Including patients who could have had other nonfatal events or died.

#NNT was 91; NNT=1/ARR; ARR=6.9%-5.8%=1.1%; NNT=1/0.011=90.9.

  • Secondary efficacy end point of CV death at 12 months for BRILINTA plus aspirin vs clopidogrel plus aspirin: Events per 1000 patient years 45 vs 57, respectively1

**Hazard ratio derived from a Cox proportional-hazards model on data from the primary and secondary end points.2

PLATO SECONDARY EFFICACY END POINT: CV DEATH AT 12 MONTHS1,2§

**K-M rate is the rate of first events only.

††NNT was 91; NNT=1/ARR; ARR=5.1%–4.0%=1.1%; NNT=1/0.011=90.9.

  • Secondary efficacy end point of CV death at 12 months for BRILINTA plus aspirin vs clopidogrel plus aspirin: Events per 1000 patient years 45 vs 57, respectively1

**Hazard ratio derived from a Cox proportional-hazards model on data from the primary and secondary end points.2

*PLATO STUDY DESCRIPTION

  • Study treatments: BRILINTA (180-mg loading dose, 90 mg twice daily thereafter) and clopidogrel (300-mg to 600-mg loading dose, 75 mg daily thereafter) in combination with aspirin and other standard therapies
  • Number/Type of patients: 18,624 patients admitted to the hospital with ACS
  • Primary efficacy end point: Composite CV death, MI, and stroke
  • Treatment duration: Patients were treated for at least 6 months and up to 12 months
  • Key exclusion criteria:
    • Previous intracranial hemorrhage
    • Gastrointestinal bleeding within 6 months
    • Known bleeding diathesis or coagulation disorder or required treatment with anticoagulants

*VIEW THE PLATO STUDY DESCRIPTION

*VIEW THE PLATO STUDY DESCRIPTION

BRILINTA SAVES MORE LIVES THAN CLOPIDOGREL BY REDUCING CV DEATH AT 12 MONTHS2

ADDITIONAL SECONDARY EFFICACY END POINTS AT 12 MONTHS1

EVENTS/1000 PATIENT YEARS OUTCOMES AT 12 MONTHS (K-M%)
BRILINTA 90 MG + ASPIRIN (N=9333) CLOPIDOGREL+ ASPIRIN (N=9291) BRILINTA 90 mg + aspirin (N=9333) Clopidogrel + aspirin (N=9291) HR (95% CI)** P VALUE
STROKE‡‡ 16 14 1.5 1.3 1.17 (0.91-1.52) 0.22
ALL-CAUSE MORTALITY 51 65 4.5 5.9 0.78 (0.69-0.89) 0.0003§§

**Hazard ratio derived from a Cox proportional-hazards model on data from the primary and secondary end points.2

‡‡Including patients who could have had other nonfatal events or died.

§§Due to the hierarchical test sequence in PLATO, all-cause mortality was an exploratory analysis and, therefore, the P value is nominal.1

BLEEDING OUTCOMES FOR BRILINTA COMPARED WITH CLOPIDOGREL IN THE PLATO STUDY1

PLATO-DEFINED NON–CABG-RELATED BLEEDING1

Non–CABG-related bleeding ratesa BRILINTA 90 mg + aspirin (N=9235) % (n) patients with event Clopidogrel + aspirin (N=9186) % (n) patients with event
PLATO major + minor 7.7 (713) 6.2 (567)
Major 3.9 (362) 3.3 (306)
Fatal/life-threatening 1.9 (171) 1.6 (151)
Fatal 0.2 (15) 0.2 (16)
Intracranial hemorrhage (fatal/life-threatening) 0.3 (26) 0.2 (15)
  • About half of non–CABG-related major bleeding events were in the first 30 days1

PLATO SAFETY END POINTS: PLATO-DEFINED CABG-RELATED BLEEDING1

CABG-related bleeding ratesa BRILINTA 90 mg + aspirin (N=770) n (%) patients with event Clopidogrel + aspirin (N=814) n (%) patients with event
PLATO total major 626 (81.3) 666 (81.8)
Fatal/life-threatening 337 (43.8) 350 (43.0)
Fatal 6 (0.8) 7 (0.9)
  • The PLATO trial did not show an advantage for BRILINTA 90 mg compared with clopidogrel for CABG-related bleeding1
  • Rates of major fatal/life-threatening CABG-related bleeding were similar between BRILINTA 90 mg and clopidogrel when study drug was withheld 1-5 days before CABG surgery1
  • When antiplatelet therapy was stopped 5 days before CABG, major bleeding occurred in 75% of patients receiving BRILINTA 90 mg and in 79% of patients receiving clopidogrel1
    • aPLATO used the following bleeding severity categorization1:
    • PLATO minor bleed: requires medical intervention to stop or treat bleeding
    • PLATO major bleed: any one of the following: fatal; intracranial; intrapericardial with cardiac tamponade; hypovolemic shock or severe hypotension requiring intervention; significantly disabling (eg, intraocular with permanent vision loss); associated with a decrease in Hb of at least 3 g/dL (or a fall in Hct of at least 9%); transfusion of 2 or more units
    • PLATO major bleed, fatal/life-threatening: any major bleed as described above and associated with a decrease in Hb of more than 5 g/dL (or a fall in Hct of at least 15%); transfusion of 4 or more units

Related links

Review additional safety data from the PLATO trial

See how real-world evidence confirms the PLATO results

View data in patients with a history of MI

Tab

THROMBOTIC CV EVENTS IN THE FINAL DIAGNOSIS SUBGROUP2

NSTEMI SUBGROUP COMPOSITE END POINT: AT 12 MONTHS2

¶¶Excluding silent MI.

##NNT was 40; NNT=1/ARR; ARR=13.9%?11.4%=2.5%; NNT=1/0.025=40.2

NSTEMI SUBGROUP COMPOSITE END POINT: AT 12 MONTHS2

Thrombotic CV events in the final diagnosis subgroup

¶¶Excluding silent MI.

##NNT was 40; NNT=1/ARR; ARR=13.9%?11.4%=2.5%; NNT=1/0.025=40.2

*PLATO STUDY DESCRIPTION

  • Study treatments: BRILINTA (180-mg loading dose, 90 mg twice daily thereafter) and clopidogrel (300-mg to 600-mg loading dose, 75 mg daily thereafter) in combination with aspirin and other standard therapies
  • Number/Type of patients: 18,624 patients admitted to the hospital with ACS
  • Primary efficacy end point: Composite CV death, MI, and stroke
  • Treatment duration: Patients were treated for at least 6 months and up to 12 months
  • Key exclusion criteria:
    • Previous intracranial hemorrhage
    • Gastrointestinal bleeding within 6 months
    • Known bleeding diathesis or coagulation disorder or required treatment with anticoagulants

*VIEW THE PLATO STUDY DESCRIPTION

*VIEW THE PLATO STUDY DESCRIPTION

Get more information on NSTEMI risk compared to STEMI

Additional final diagnosis subgroup composite end point K-M% at 12 months2

  • BRILINTA 90 mg plus aspirin vs clopidogrel plus aspirin:
    • STEMI 8.5% (N=3496) vs 10.1% (N=3530), respectively (HR: 0.84; 95% CI: 0.72-0.98)
    • UA 8.6% (N=1549) vs 9.1% (N=1563), respectively (HR: 0.96; 95% CI: 0.75-1.22)

PLATO was not designed or powered to demonstrate the efficacy or safety of BRILINTA compared with clopidogrel in specific subgroups. Subgroup analyses were performed to evaluate consistency of results in different cohorts. Analysis must be interpreted cautiously, as differences can reflect the play of chance among a large number of analyses. The final diagnosis subgroup was based on postrandomized determinations.2

PLATO-DEFINED NON‒CABG-RELATED TOTAL MAJOR BLEEDING IN FINAL DIAGNOSIS SUBGROUP K-M% AT 12 MONTHS4

BRILINTA 90 mg + aspirin Clopidogrel + aspirin HR 95% CI
NSTEMI 5.1 4.4 1.17 0.94-1.45
STEMI 4.0 3.3 1.17 0.91-1.51
UA 3.9 3.2 1.29 0.85-1.95
  • Within subgroups, non‒CABG-related total major bleeding rates were higher for BRILINTA vs clopidogrel4

Related links

Review additional safety data from the PLATO trial

See how real-world evidence confirms the PLATO results

View data in patients with a history of MI

Tab

PLATO STUDY DESCRIPTION

BRILINTA 90 mg plus aspirin was studied vs clopidogrel plus aspirin in more than 18,000 patients, including STEMI (ST-elevation myocardial infarction), NSTEMI (non–ST-elevation myocardial infarction), and UA (unstable angina) patients, across 43 countries and 862 sites in the PLATO (PLATelet inhibition and patient Outcomes) study.2

Patients were treated for at least 6 months and up to 12 months. Patients were excluded if they had a previous intracranial hemorrhage, had gastrointestinal bleeding within 6 months, had a known bleeding diathesis or coagulation disorder, or required treatment with anticoagulants. BRILINTA and clopidogrel were studied with aspirin and other standard therapies.1

PLATO was designed to mirror real-world clinical practice across ACS diagnoses and medical or invasive treatment approaches.5***

***PLATO included both medical and invasive (PCI or CABG) treatment approaches. Patients who received fibrinolytic therapy within the previous 24 hours or who had a need for chronic oral anticoagulation therapy were excluded.

Related links

Review bleeding outcomes of the PLATO trial

See how real-world evidence confirms the PLATO results

View data in patients with a history of MI

SUPERIOR TO CLOPIDOGREL: 45,000 PATIENTS CONFIRM IT

PATIENTS STUDIED IN A REAL-WORLD REGISTRY CONFIRMED THE SIGNIFICANT REDUCTIONS IN CV EVENTS FOR BRILINTA VS CLOPIDOGREL SEEN IN THE PLATO TRIAL6

TICAGRELOR REAL-WORLD STUDY: COMPOSITE OF ALL-CAUSE DEATH, READMISSION FOR MI, OR STROKE AT 24 MONTHS6

Patients studied in real-world registry confirmed the significant reductions in CV events for BRILINTA vs Clopidogrel seen in the Plato Trial.

Final values are adjusted for hospital and calendar time, age, sex, discharge medication, in-hospital course, presentation characteristics, and preexisting comorbidities.

TICAGRELOR REAL-WORLD STUDY:
 COMPOSITE OF ALL-CAUSE DEATH, READMISSION FOR MI, OR STROKE AT 24 MONTHS6

Patients studied in real-world registry confirmed the significant reductions in CV events for BRILINTA vs Clopidogrel seen in the Plato Trial.

Final values are adjusted for hospital and calendar time, age, sex, discharge medication, in-hospital course, presentation characteristics, and preexisting comorbidities.

  • This was an observational study in patients enrolled in the Swedish Web system for Enhancement and Development of Evidence-based care in Heart disease Evaluated According to Recommended Therapies (SWEDEHEART) registry6
  • Acute MI patients enrolled in the SWEDEHEART registry were discharged on aspirin and either BRILINTA or clopidogrel from 2010 to 2013 (N=45,073) and followed for 24 months. Patients undergoing CABG were excluded from this analysis6
  • Sensitivity analysis conducted at 12 months showed results consistent with the primary efficacy outcome6

View limitations of the real-world patient registry

BLEEDING OUTCOMES FROM PATIENTS STUDIED IN A REAL-WORLD REGISTRY WERE CONSISTENT WITH THOSE SEEN IN PLATO6,7

TICAGRELOR REAL-WORLD STUDY: BLEEDING REQUIRING HOSPITALIZATION6,7

CUMULATIVE PROBABILITY OF EVENTS PER 100 PATIENT-YEARS

BRILINTA 90 mg + aspirin Clopidogrel + aspirin
12 months††† 4.43 3.85
24 months‡‡‡ 5.5 5.2

†††The 12-month bleeding outcome estimate was based on the assumption of similar proportions of event rates for years 1 and 2.

‡‡‡Adjusted HR: 1.20 (95% CI: 1.04-1.40).

Bleeding was defined by the patient receiving treatment for at least 1 of the following: hemorrhagic stroke, gastrointestinal bleeding, anemia-related bleeding, or other bleeding.6

  • The absolute bleeding risk was lower than that observed in the PLATO trial, possibly due to underreporting6
  • This was an observational study in a subset of patients enrolled in the Swedish Web system for Enhancement and Development of Evidence-based care in Heart disease Evaluated According to Recommended Therapies (SWEDEHEART) registry6
  • Acute MI patients enrolled in the SWEDEHEART registry were discharged on aspirin and either BRILINTA or clopidogrel from 2010 to 2013 (N=45,073) and followed for 24 months. Patients undergoing CABG were excluded from this analysis6
  • Sensitivity analysis conducted at 12 months showed results consistent with the primary efficacy outcome6

Related links

Review additional safety data from the real-world patient registry

See established clinical trial data for BRILINTA

View data in patients with a history of MI

COMPARISON OF THE REAL-WORLD PATIENT REGISTRY WITH THE PLATO CLINICAL TRIAL

TICAGRELOR REAL-WORLD STUDY6 PLATO1,2
TRIAL DESIGN Observational study using Swedish Web system for Enhancement and Development of Evidence-based care in Heart disease Evaluated According to Recommended Therapies (SWEDEHEART) registry Randomized, double-blind, controlled comparative study
PATIENT TYPE Acute MI patients enrolled in the SWEDEHEART registry discharged on aspirin and either BRILINTA or clopidogrel from 2010 to 2013 International ACS patients hospitalized with or without ST-segment elevation, with an onset of symptoms within 24 hours
NUMBER OF PATIENTS 45,073 18,624
STUDY PERIOD 24 months 12 months
DURATION
Intended DAPT duration BRILINTA 90 mg + aspirin clopidogrel + aspirin
3 months 3.3% 17.6%
6 months 3.8% 7.0%
12 months 83.8% 50.9%
Median 277 days (up to 12 months)
PRIMARY EFFICACY END POINT Composite of all-cause mortality, readmission for MI, or stroke§§§ Composite of CV death, MI, or stroke
KEY SECONDARY EFFICACY END POINTS All-cause mortality, readmission for MI, or stroke CV death, MI, stroke, all-cause mortality
PRIMARY SAFETY END POINT Readmission with bleeding PLATO-defined total major bleeding
BRILINTA DOSAGE 90 mg twice daily 90 mg twice daily
ASPIRIN DOSAGE 75 mg daily 75-100 mg daily maintenance dose (after stent placement up to 325 mg daily was allowed for up to 6 months)
KEY DIFFERENCES IN DEMOGRAPHIC INFORMATION (REGISTRY VS PLATO) Registry study population:
  • 8 years older (70 vs 62 years)
  • higher incidence of previous stroke (10.8% vs 3.9%)
  • higher incidence of previous heart failure (10.3% vs 5.6%)
INCLUSION CRITERIA Patients with cardiac marker verified acute MI and symptoms admitted to a cardiac unit in Sweden and discharged on dual antiplatelet therapy (DAPT) with aspirin and either ticagrelor or clopidogrel Patients hospitalized within 24 hours of symptom onset: unstable angina (UA), non–ST-elevation MI (NSTEMI), or ST-elevation MI (STEMI)
KEY EXCLUSION CRITERIA Treatment with oral anticoagulant (OAC) or coronary artery bypass grafting (CABG) during hospitalization Previous intracranial hemorrhage, gastrointestinal bleeding within 6 months, known bleeding diathesis or coagulation disorder, or required treatment with anticoagulants

§§§Sensitivity analysis was conducted at 12 months.6

IMPORTANT LIMITATIONS OF THE REAL-WORLD REGISTRY

  • This was an observational registry trial, and, while analyses were adjusted for confounding factors, the results are subject to potential bias and should be interpreted with caution
  • The trial was conducted only in Sweden, and there may be differences between Swedish and US populations and treatment practices
  • The actual treatment duration, attrition, and crossover data were not available because the analysis was based on planned, not actual, duration of treatment (planned duration was 12 months or less for 90.9% and 75.5% of patients who received BRILINTA and clopidogrel, respectively)
  • For MI analysis, a 28-day blanking period was applied at discharge to avoid index events being counted twice (through duplication between hospital transfers or attribution to index events for any early readmissions)
  • The absolute bleeding risk was lower than that observed in trials, possibly due to underreporting

Related links

Review the bleeding outcomes seen with BRILINTA in a real-world patient registry

See established clinical trial data for BRILINTA

View data in patients with a history of MI

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BRILINTA: HCP Indications, Dosage and Important Safety Information effective 11/20

Instructions for Indication and Dosing: Each asset must contain the ACS/Prior MI indication. Assets may also contain either the CAD or stroke indication (or both). Assets cannot contain just the stroke or CAD indication(s). Each asset must contain the ACS/Prior MI dosing and the corresponding dosing for CAD/Stroke if those indications are included in the asset.

INDICATIONS

BRILINTA is indicated to reduce the risk 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 risk of stent thrombosis in patients who have been stented for treatment of ACS.

BRILINTA is indicated to reduce the risk of a first MI or stroke in patients with coronary artery disease (CAD) at high risk for such events. While use is not limited to this setting, the efficacy of ticagrelor was established in a population with type 2 diabetes.

BRILINTA is indicated to reduce the risk of stroke in patients with acute ischemic stroke (NIH Stroke Scale ≤5) or high-risk transient ischemic attack (TIA).

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.

In patients with CAD but no prior stroke or MI, administer 60 mg twice daily.

In patients with acute ischemic stroke or high-risk TIA, initiate treatment with a 180-mg loading dose of BRILINTA and then continue with 90 mg twice daily for up to 30 days. The treatment effect accrued early in the course of therapy. Use BRILINTA with a loading dose of aspirin (300 to 325 mg)

Use BRILINTA with a daily maintenance dose of aspirin of 75-100 mg.

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

WARNINGS:

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 IN PATIENTS WITH ACS

  • 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 more frequently with BRILINTA than in patients treated with control agents. Dyspnea from BRILINTA is often self-limiting
  • In patients being treated for coronary artery disease, 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. Clinical trials excluded patients at increased risk of bradyarrhythmias not protected by a pacemaker, and they may be at increased risk of developing bradyarrhythmias
  • 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
  • In patients with Heparin Induced Thrombocytopenia (HIT): False negative results for HIT-related platelet functional tests, including the heparin-induced platelet aggregation (HIPA) assay, have been reported with BRILINTA. BRILINTA is not expected to impact PF4 antibody testing for HIT

ADVERSE REACTIONS

  • The most common adverse reactions (>5%) associated with the use of BRILINTA included bleeding and dyspnea

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
  • As with other oral P2Y12 inhibitors, co-administration of opioid agonists delay and reduce the absorption of ticagrelor. Consider use of a parenteral anti-platelet in ACS patients requiring co-administration
  • 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

SPECIAL POPULATIONS

  • Lactation: Breastfeeding not recommended

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

References: 1. BRILINTA® (ticagrelor) [package insert]. Wilmington, DE: AstraZeneca Pharmaceuticals LP; 2020. 2. Wallentin L, Becker RC, Budaj A, et al; for the PLATO Investigators. Ticagrelor versus clopidogrel in patients with acute coronary syndromes. N Engl J Med. 2009;361(11):1045-1057 and Supplementary Appendix. 3. Sahlén A, Varenhorst C, Lagerqvist B, et al. Outcomes in patients treated with ticagrelor or clopidogrel after acute myocardial infarction: experiences from SWEDEHEART registry. Eur Heart J. 2016;37(44):3335-3342. 4. Bonaca MP, Bhatt DL, Cohen M, et al, for the PEGASUS-TIMI 54 Steering Committee and Investigators. Long-term use of ticagrelor in patients with prior myocardial infarction. N Engl J Med. 2015;372(19):1791-1800. 5. Steg PG, Bhatt DL, Simon T, et al; for the THEMIS Steering Committee and Investigators. Ticagrelor in patients with stable coronary disease and diabetes. N Engl J Med. 2019;381(14):1309-1320.

References: 1. BRILINTA® (ticagrelor) [package insert]. Wilmington, DE: AstraZeneca Pharmaceuticals LP; 2020. 2. Wallentin L, Becker RC, Budaj A, et al; for the PLATO Investigators. Ticagrelor versus clopidogrel in patients with acute coronary syndromes. N Engl J Med. 2009;361(11):1045-1057 and Supplementary Appendix. 3. Sahlén A, Varenhorst C, Lagerqvist B, et al. Outcomes in patients treated with ticagrelor or clopidogrel after acute myocardial infarction: experiences from SWEDEHEART registry. Eur Heart J. 2016;37(44):3335-3342. 4. Bonaca MP, Bhatt DL, Cohen M, et al, for the PEGASUS-TIMI 54 Steering Committee and Investigators. Long-term use of ticagrelor in patients with prior myocardial infarction. N Engl J Med. 2015;372(19):1791-1800.

References: 1. BRILINTA® (ticagrelor) [package insert]. Wilmington, DE: AstraZeneca Pharmaceuticals LP; 2020. 2. Steg PG, Bhatt DL, Simon T, et al; for the THEMIS Steering Committee and Investigators. Ticagrelor in patients with stable coronary disease and diabetes. N Engl J Med. 2019;381(14):1309-1320. 3. Fingertip Formulary.® July 11, 2020.

ACS=acute coronary syndrome; CV=cardiovascular; MI=myocardial infarction; PEGASUS=Prevention of Cardiovascular Events in Patients With Prior Heart Attack Using Ticagrelor Compared to Placebo on a Background of Aspirin; PLATO=PLATelet inhibition and patient Outcomes; SWEDEHEART=Swedish Web System for Enhancement and Development of Evidence-Based Care in Heart Disease Evaluated According to Recommended Therapies; THEMIS=Effect of Ticagrelor on Health Outcomes in DiabEtes Mellitus Patients Intervention Study; T2D=type 2 diabetes.

ACS=acute coronary syndrome; CV=cardiovascular; MI=myocardial infarction; PEGASUS=Prevention of Cardiovascular Events in Patients With Prior Heart Attack Using Ticagrelor Compared to Placebo on a Background of Aspirin; PLATO=PLATelet inhibition and patient Outcomes; SWEDEHEART=Swedish Web System for Enhancement and Development of Evidence-Based Care in Heart Disease Evaluated According to Recommended Therapies.

ACS=acute coronary syndrome; ARR=absolute risk reduction; ARI=absolute risk increase; CABG=coronary artery bypass graft; CI=confidence interval; Hb=hemoglobin; Hct=hematocrit; HR= hazard ratio; K-M=Kaplan-Meier; PLATO=PLATelet inhibition and patient Outcomes; RRR=relative risk reduction.