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
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CURVES SEPERATED BY 30 DAYS AND CONTINUES TO DIVERGE THROUGHOUT THE 12-MONTH TREATMENT PERIOD1,2
BRILINTA HELPED PROTECT MORE PATIENTS THAN CLOPIDOGREL FROM SUFFFERING ANOTHER HEART ATTACK2
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.
†Excluding silent Ml.
‡Hazard ratio derived from a Cox proportional-hazards model on data from the primary and secondary end points.2
CURVES SEPARATED BY 30 DAYS AND CONTINUED TO DIVERGE THROUGHOUT THE 12-MONTH TREATMENT PERIOD1,2
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) |
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) |
§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.
**Hazard ratio derived from a Cox proportional-hazards model on data from the primary and secondary end points.2
BRILINTA HELPED PROTECT MORE PATIENTS THAN CLOPIDOGREL FROM SUFFERING ANOTHER HEART ATTACK2
§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.
**Hazard ratio derived from a Cox proportional-hazards model on data from the primary and secondary end points.2
BRILINTA SAVES MORE LIVES THAN CLOPIDOGREL BY REDUCING CV DEATH AT 12 MONTHS2
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
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 |
0.3 (26) | 0.2 (15) |
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) |
¶¶Excluding silent MI.
##NNT was 40; NNT=1/ARR; ARR=13.9%?11.4%=2.5%; NNT=1/0.025=40.2
Get more information on NSTEMI risk compared to STEMI
Additional final diagnosis subgroup composite end point K-M% at 12 months2
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
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 |
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.
Final values are adjusted for hospital and calendar time, age, sex, discharge medication, in-hospital course, presentation characteristics, and preexisting comorbidities.
Final values are adjusted for hospital and calendar time, age, sex, discharge medication, in-hospital course, presentation characteristics, and preexisting comorbidities.
View limitations of the real-world patient registry
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
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 |
|
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:
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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
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).
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.
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.