BRILINTA Met Primary Endpoint in the Phase III THALES Trial in Stroke
January 27 2020 - 07:00AM
Business Wire
BRILINTA reduced the risk of the composite of
stroke and death after an acute ischemic stroke or transient
ischemic attack
High-level results from the Phase III THALES trial showed
AstraZeneca’s BRILINTA (ticagrelor) 90 mg used twice daily and
taken with aspirin for 30 days, reached a statistically significant
and clinically meaningful reduction in the risk of the primary
composite endpoint of stroke and death, compared to aspirin
alone.
THALES was conducted in over 11,000 patients who had a minor
acute ischemic stroke or high-risk transient ischemic attack (TIA)
in the 24 hours prior to treatment initiation. The preliminary
safety findings in the THALES trial were consistent with the known
profile of BRILINTA, with an increased bleeding rate in the
treatment arm.
Mene Pangalos, Executive Vice President, BioPharmaceuticals
R&D, said: “Results of the Phase III THALES trial showed
BRILINTA, in combination with aspirin, improved outcomes in
patients who had experienced a minor acute ischemic stroke or
high-risk transient ischemic attack. We look forward to sharing the
detailed results with health authorities.”
Dr. Clay Johnston, lead investigator for the THALES trial and
Dean of the Dell Medical School at The University of Texas at
Austin, said: “The risk of having a subsequent stroke is highest in
the first few days and weeks after a minor acute ischemic stroke or
high-risk transient ischemic attack. While an expected increase in
bleeding was observed, the findings from THALES showed that
BRILINTA, in combination with aspirin, reduced the risk of
potentially devastating events in this crucial time.”
The full THALES trial results will be presented at a forthcoming
medical meeting.
BRILINTA is not indicated in patients with minor acute ischemic
stroke or high-risk transient ischemic attack.
BRILINTA is indicated to reduce the rate of CV death, myocardial
infarction (MI), and stroke in patients with ACS or a history of
MI. 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.
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
- 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 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
- 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.
NOTES TO EDITORS
About THALES
THALES is an AstraZeneca-sponsored, randomized,
placebo-controlled, double-blinded, international, multicenter,
event-driven trial involving more than 11,000 patients to test the
hypothesis whether BRILINTA and aspirin is superior to aspirin
alone in preventing the composite of stroke and death in patients
with minor acute ischemic stroke or high-risk TIA. Patients were
randomized within 24 hours of onset of acute ischemic stroke or
high-risk TIA symptoms and followed-up for 30 days of treatment.
Trial treatments were BRILINTA 180mg loading dose on day 1 as soon
as possible after randomization, followed by 90mg twice daily on
days 2–30, or matching placebo. All patients received open-label
aspirin 300–325mg on day 1, followed by 75–100mg once daily on days
2–30. The primary efficacy outcome was the time to the composite
endpoint of stroke and death at 30 days. The primary safety outcome
is time to first severe bleeding event according to the Global
Utilization of Streptokinase and Tissue Plasminogen Activator for
Occluded Coronary Arteries (GUSTO) definition. Patients were
followed for an additional 30 days on standard of care.
About BRILINTA
BRILINTA (ticagrelor) is an oral, reversible, 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.
About AstraZeneca in CVMD
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main therapy areas and a key growth driver for the Company. By
following the science to understand more clearly the underlying
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outcomes by slowing disease progression, reducing risks and
tackling comorbidities. Our ambition is to modify or halt the
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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 &
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countries and its innovative medicines are used by millions of
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US-35105 Last updated 1/20
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