New BRILINTA indication expands treatment to
high-risk coronary patients without a history of stroke or heart
attack
AstraZeneca’s BRILINTA® (ticagrelor) has been approved in the US
to reduce the risk of a first heart attack or stroke in high-risk
patients with coronary artery disease (CAD), the most common type
of heart disease.
The approval by the US Food and Drug Administration (FDA) was
based on positive results from the Phase III THEMIS trial. The
trial showed a statistically significant reduction in the primary
composite endpoint of major adverse cardiovascular (CV) events at
36 months with aspirin plus BRILINTA 60mg versus aspirin alone in
patients with CAD and type 2 diabetes (T2D) at high-risk of a first
heart attack or stroke. The primary composite endpoint was driven
by a reduction in heart attack and stroke.
This is the first regulatory approval for aspirin plus BRILINTA
dual antiplatelet therapy in patients who have a high CV risk, but
without a history of heart attack or stroke.
Deepak L. Bhatt, MD, MPH, THEMIS trial Co-Chair, Executive
Director of Interventional Cardiovascular Programs at Brigham and
Women’s Hospital, and Professor of Medicine at Harvard Medical
School, Boston, US said: “Coronary artery disease is a potentially
life-threatening condition that causes significant morbidity in
many people. The addition of ticagrelor to aspirin offers a new
therapeutic option to decrease the likelihood of both heart attack
and stroke, a significant advance in our ability to treat these
high-risk patients.”
Gabriel Steg, MD, THEMIS trial Co-Chair and Professor at
Université de Paris, said: “THEMIS for ticagrelor was a large,
multi-national trial of more than 19,000 patients with coronary
artery disease and type 2 diabetes. Around one third of patients
with coronary artery disease have type 2 diabetes, putting them at
higher risk of heart attack or stroke, than patients without
diabetes. Today’s approval brings new hope to patients at risk of
experiencing a first heart attack or stroke.”
Ruud Dobber, Executive Vice President, BioPharmaceuticals
Business Unit, said: “Today’s approval of BRILINTA is important
news for patients with coronary artery disease who will now have a
new therapy option to reduce the risk of a first heart attack or
stroke. This new indication is a further testament to the
overwhelming science supporting BRILINTA in the management of
patients with coronary artery disease at high risk for
cardiovascular events.”
The THEMIS trial demonstrated the relative risk reduction of the
composite endpoint of heart attack, stroke and CV death by 10%
(absolute risk reduction; 0.8%, 7.7% vs 8.5%) with aspirin plus
long-term BRILINTA compared to aspirin alone in patients who had
CAD and T2D without a history of heart attack or stroke. While this
indication is not limited to this setting, the efficacy of BRILINTA
was established in a population with T2D in the THEMIS trial. The
safety profile for BRILINTA was consistent with the known profile
of the medicine with an increased risk of bleeding events
observed.
The data from the THEMIS trial and the THEMIS-PCI sub-analysis
were published in The New England Journal of Medicine and The
Lancet respectively.
Regulatory submissions to expand the approved indication for
BRILINTA based on the THEMIS trial are also under regulatory review
in the EU, Japan and China.
AstraZeneca also recently announced the high-level results from
the Phase III THALES trial that showed aspirin plus BRILINTA 90mg
reduced the risk of the composite of stroke and death at 30 days
after an acute ischemic stroke or transient ischemic attack,
compared to aspirin alone.
BRILINTA is not indicated in patients with minor acute ischemic
stroke or high-risk transient ischemic attack.
BRILINTA is approved in more than 110 countries for the
prevention of atherothrombotic events in adult patients with acute
coronary syndrome (ACS), and in more than 70 countries for the
secondary prevention of CV events among high-risk patients who have
experienced a prior myocardial infarction.
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.
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. 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
- 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
- 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.
CAD and T2D
CAD is the most common type of heart disease. Ischemic heart
disease is the leading cause of healthy life years lost due to
disability in men and the second cause in women worldwide. The
disease burden of atherosclerosis is significantly higher in
patients with CAD and T2D than in CAD patients without T2D.
THEMIS
THEMIS is an AstraZeneca-sponsored, multi-national, randomized,
double-blinded Phase III trial in patients with CAD and T2D with no
prior heart attack or stroke. More than 19,000 patients were
randomized across 42 countries in Europe, Asia, Africa, North and
South America. THEMIS was designed to test the hypothesis that
aspirin daily plus BRILINTA 60mg twice daily would reduce MACE
(major adverse cardiac events), compared with aspirin alone. CAD
was defined as a history of percutaneous coronary intervention
(PCI), coronary artery bypass surgery, or at least a 50% narrowing
of a coronary artery. Additionally, THEMIS-PCI is a clinically
meaningful and prespecified sub-analysis of patients (11,154 which
is 58% of total patients) who had previously undergone percutaneous
coronary intervention (PCI).
BRILINTA
BRILINTA (ticagrelor) is an oral, reversibly binding,
direct-acting P2Y12 receptor antagonist that works by inhibiting
platelet activation. BRILINTA, together with aspirin, has been
shown to significantly reduce the risk of major adverse
cardiovascular events (myocardial infarction [MI], stroke or CV
death) in patients with acute coronary syndrome (ACS) or a history
of MI.
AstraZeneca in CV, Renal & Metabolism (CVMD)
CV, renal and metabolism together form one of AstraZeneca’s main
therapy areas and a key growth driver for the Company. By following
the science to understand more clearly the underlying links between
the heart, kidneys and pancreas, AstraZeneca is investing in a
portfolio of medicines to protect organs and improve outcomes by
slowing disease progression, reducing risks and tackling
co-morbidities. Our ambition is to modify or halt the natural
course of CVMD diseases and potentially regenerate organs and
restore function, by continuing to deliver transformative science
that improves treatment practices and CV health for millions of
patients worldwide.
About AstraZeneca
AstraZeneca is a global, science-led biopharmaceutical company
that focuses on the discovery, development and commercialization of
prescription medicines, primarily for the treatment of diseases in
three therapy areas - Oncology, Cardiovascular, Renal &
Metabolism and Respiratory. AstraZeneca operates in over 100
countries and its innovative medicines are used by millions of
patients worldwide. For more information, please visit
www.astrazeneca-us.com and follow us on Twitter @AstraZenecaUS.
Disclosure
Brigham and Women’s Hospital received research funding for Dr
Bhatt’s role as co-Chair of THEMIS and THEMIS-PCI.
US-40170 Last Updated 6/20
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