New data on cardiovascular effects of
long-term BRILINTA use in patients with a history of heart
attack
Data from 20 abstracts further highlight
AstraZeneca’s holistic approach to care in cardiovascular, renal
and metabolic diseases
AstraZeneca will present 20 abstracts including a late-breaking
oral presentation on the full results from the Phase III
cardiovascular (CV) outcomes trial (CVOT) DECLARE (Dapagliflozin
Effect on Cardiovascular Events)-TIMI 58, the broadest SGLT2
inhibitor CVOT conducted to date, as well as new research from the
Company’s Cardiovascular, Renal & Metabolism (CVMD) therapy
area at the American Heart Association (AHA) Scientific Sessions,
November 10-12, 2018, in Chicago, Illinois, USA.
New evidence will build on broad clinical research from
AstraZeneca that aims to help redefine the management of CVMD
diseases and address the need for a more proactive and holistic
approach to patient care. Presentations will include findings from
some of the largest trials in broad patient populations with
FARXIGA (dapagliflozin) in type 2 diabetes (T2D), BRILINTA
(ticagrelor) in patients with a history of heart attack, and in
hyperkalemia.
Danilo Verge, Vice President, Cardiovascular, Renal &
Metabolism, Global Medical Affairs, said: “An estimated 20 million
people each year die from cardiovascular, renal and metabolic
diseases, yet shared risk factors are frequently not diagnosed
or addressed holistically.1,2,3 Our data at AHA reflect an
integrated approach to managing the needs of patients living with
type 2 diabetes and risk of cardiovascular or renal disease, and
those with a history of cardiovascular disease at acute and
long-term risk of recurrence. We stand firmly behind our mission to
provide new solutions earlier in disease management to these
patients at risk for multiple complications.”
DECLARE-TIMI 58: a landmark CVOT evaluating CV risk in
patients with T2D
Clinical trial results showing the safety and efficacy of
FARXIGA vs. placebo on primary CV and secondary renal efficacy
outcomes in adults with T2D who have multiple CV risk factors or
established CV disease, will be presented in a late-breaking oral
presentation (Late Breaking Abstract #19485). DECLARE-TIMI 58
evaluated the CV outcomes of FARXIGA vs. placebo over a
period of up to five years, across 33 countries and in more than
17,000 adults with T2D with multiple CV risk factors or established
CV disease.
In September 2018, AstraZeneca announced that FARXIGA met
its primary safety endpoint of non-inferiority for major adverse
cardiovascular events (MACE) and achieved a
statistically-significant reduction in the composite endpoint of
hospitalization for heart failure (hHF) or CV death, one of the two
primary efficacy endpoints. Additionally, fewer MACE events were
observed with FARXIGA for the other primary efficacy
endpoint, however, this did not reach statistical significance.
Clinical trial results presented at AHA Scientific Sessions 2018
will include additional details on the primary CV safety and
efficacy, as well as secondary renal efficacy outcomes from
DECLARE-TIMI 58. FARXIGA is not indicated to reduce the risk of CV
events, hHF or renal outcomes.
Three new sub-analyses from the PEGASUS-TIMI 54 trial will also
be presented. The trial compared BRILINTA (90mg or 60mg twice
daily) plus aspirin vs. aspirin alone in 21,162 patients with prior
(1 to 3 years) heart attack. The sub-analyses evaluate:
- Whether clinical characteristics
predicting bleeding and ischemic risk identify subgroups of
patients who may derive benefit from long-term treatment with
BRILINTA, with a lower risk of major bleeding (Poster #Sa2100)
- The effects of long-term use of
BRILINTA in patients who have had a heart attack and who did not
receive a coronary stent vs. those who did receive a coronary stent
placement (Oral Presentation #102)
- The use of high-sensitivity cardiac
troponin to identify patients who are at a higher-risk of major CV
events (Oral Presentation #100)
Data will also be presented on potential risk factors for
repeated or persistent hyperkalemia (Poster # SuMDP65).
Key abstracts at the AHA Scientific Sessions 2018:
Abstract title Presentation details
FARXIGA
The Dapagliflozin Effect on
CardiovascularEvents (DECLARE)–TIMI 58 Trial
Late Breaking Abstract #19485
Saturday November 10, 3:45 PM - 4:00
PM
Session: LBS.02. Late Breaking Clinical
Trial:Novel Approaches to CV Prevention
BRILINTA
Long-Term Secondary Prevention with
Ticagrelorfor Prior Myocardial Infarction in Patients with
noCoronary Stenting: A Sub-analysis fromPEGASUS TIMI 54
Oral Presentation #102Sunday
November 11, 4:15 PM - 4:25 PM
Session: AC.AOS.01, S103bc. Advances inthe
Prediction and Modification ofCardiovascular Disease Risk
High-sensitivity Cardiac Troponin at
AnyDetectable Concentration Identifies Higher Riskof Major
Cardiovascular Events in Patients withStable Ischemic Heart
Disease
Oral Presentation #100
November 11, 3:45 PM - 3:55 PM
Session: AC.AOS.01, S103bc. Advances inthe
Prediction and Modification ofCardiovascular Disease Risk
Method of Assessing Medication
Persistenceand Clinical Outcomes: A Comparison of PatientReport and
Pharmacy Fill Data from theARTEMIS Trial
Oral Presentation #452
November 11, 2:45 PM - 2:50 PM
Session: QU.RFO1. ACS Top QCORAbstracts:
Rapid Fire
Impact of Coronary Artery Disease Severity
onRisk of Cardiovascular Disease in Type 2Diabetes Patients: A
Swedish NationwideObservational Study
Poster # Su1297, 1297
November 11, 10:30 AM - 11:45 AM
Session: QU.APS.03. Acute and
ChronicCoronary Artery Disease: Quality Care andOutcomes
Patient Selection for Long-Term Prevention
ofLimb Ischemic Events
Oral Presentation (Rapid Fire)
#419
November 10, 2:15 PM - 3:30 PM
Session: VA.RFO1. Understanding Risk
andMechanisms of Critical Limb Ischemia:Lessons from the Long
CLImb
Patient Selection for Long-Term
SecondaryPrevention with Ticagrelor: Insights fromPEGASUS-TIMI
54
Poster #Sa2100, 2100
November 10, 2:15 PM - 3:30 PM
Session: AC.APS.09. Pharmacotherapy inACS
and Stable Ischemic Heart Disease
Caffeine and Dyspnea With Ticagrelor: A
Sub-analysis From PEGASUS TIMI-54 Trial
Poster #2097, Sa2097
November 10, 2:15 PM - 3:30 PM
Session: AC.APS.09. Pharmacotherapy inACS
and Stable Ischemic Heart Disease
The 'Halo Effect" of a P2Y12
InhibitorCopayment Reduction Intervention onAdherence and
Persistence with otherCardiovascular medications: Results from
theARTEMIS Cluster Randomized Trial
Poster #Sa2098, 2098
November 10, 2:15 PM - 3:30 PM
Session: AC.APS.09. Pharmacotherapy inACS
and Stable Ischemic Heart Disease
Hyperkalemia
What Characterizes the Patients who
DevelopRepeated or Persistent Hyperkalemia?
Poster # SuMDP65
November 11, 11:45 AM - 12:55 PM
Session: HF.MDP2. Interesting Topics
inHeart Failure and Cardiomyopathy
The full list of scientific data can be accessed on the AHA 2018
Online Planner here. You can also follow us live during the event
on Twitter and LinkedIn.
INDICATION AND LIMITATIONS OF USE FOR FARXIGA (dapagliflozin)
tablets 5 mg and 10 mg
FARXIGA is indicated as an adjunct to diet and exercise to
improve glycemic control in adults with type 2 diabetes
mellitus.
FARXIGA is not recommended for patients with type 1 diabetes
mellitus or for the treatment of diabetic ketoacidosis.
IMPORTANT SAFETY INFORMATION FOR FARXIGA
Contraindications
- Prior serious hypersensitivity reaction
to FARXIGA
- Severe renal impairment (eGFR <30
mL/min/1.73 m2), end-stage renal disease, or patients on
dialysis
Warnings and Precautions
- Hypotension: FARXIGA causes
intravascular volume contraction, and symptomatic hypotension can
occur. Assess and correct volume status before initiating FARXIGA
in patients with impaired renal function, elderly patients, or
patients on loop diuretics. Monitor for hypotension
- Ketoacidosis has been
reported in patients with type 1 and type 2 diabetes receiving
FARXIGA. Some cases were fatal. Assess patients who present with
signs and symptoms of metabolic acidosis for ketoacidosis,
regardless of blood glucose level. If suspected, discontinue
FARXIGA, evaluate and treat promptly. Before initiating FARXIGA,
consider risk factors for ketoacidosis. Patients on FARXIGA may
require monitoring and temporary discontinuation in situations
known to predispose to ketoacidosis
- Acute Kidney Injury and Impairment
in Renal Function: FARXIGA causes intravascular volume
contraction and renal impairment, with reports of acute kidney
injury requiring hospitalization and dialysis. Consider temporarily
discontinuing in settings of reduced oral intake or fluid losses.
If acute kidney injury occurs, discontinue and promptly
treat.FARXIGA increases serum creatinine and decreases eGFR.
Elderly patients and patients with impaired renal function may be
more susceptible to these changes. Before initiating FARXIGA,
evaluate renal function and monitor periodically. FARXIGA is not
recommended in patients with an eGFR persistently between 30
and <60 mL/min/1.73 m2
- Urosepsis and
Pyelonephritis: SGLT2 inhibitors increase the risk for
urinary tract infections [UTIs] and serious UTIs have been reported
with FARXIGA. Evaluate for signs and symptoms of UTIs and treat
promptly
- Hypoglycemia: FARXIGA can
increase the risk of hypoglycemia when coadministered with insulin
and insulin secretagogues. Consider lowering the dose of these
agents when coadministered with FARXIGA
- Necrotizing Fasciitis of the
Perineum (Fournier’s Gangrene): Rare but serious,
life-threatening cases have been reported in patients receiving
SGLT2 inhibitors including FARXIGA. Cases have been reported in
females and males. Serious outcomes have included hospitalization,
surgeries, and death. Assess patients presenting with pain or
tenderness, erythema, swelling in the genital or perineal area,
along with fever or malaise. If suspected, institute prompt
treatment and discontinue FARXIGA.
- Genital Mycotic
Infections: FARXIGA increases the risk of genital mycotic
infections, particularly in patients with prior genital mycotic
infections. Monitor and treat appropriately
- Increases in Low-Density Lipoprotein
Cholesterol (LDL-C) occur with FARXIGA. Monitor LDL-C and
treat per standard of care
- Bladder cancer: An
imbalance in bladder cancers was observed in clinical trials. There
were too few cases to determine whether the emergence of these
events is related to FARXIGA, and insufficient data to determine
whether FARXIGA has an effect on pre-existing bladder tumors.
FARXIGA should not be used in patients with active bladder cancer.
Use with caution in patients with a history of bladder cancer
- Macrovascular
Outcomes: There have been no clinical studies establishing
conclusive evidence of macrovascular risk reduction with
FARXIGA
Adverse Reactions
In a pool of 12 placebo-controlled studies, the most common
adverse reactions (≥5%) associated with FARXIGA 5 mg, 10 mg, and
placebo respectively were female genital mycotic infections (8.4%
vs. 6.9% vs. 1.5%), nasopharyngitis (6.6% vs. 6.3% vs. 6.2%), and
urinary tract infections (5.7% vs. 4.3% vs. 3.7%).
Use in Specific Populations
- Pregnancy: Advise females
of potential risk to a fetus especially during the second and third
trimesters.
- Lactation: FARXIGA is not
recommended when breastfeeding
Please read US Full Prescribing
Information and Medication
Guide for FARXIGA
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
- 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
- As with other oral P2Y12 inhibitors,
coadministration 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
INDICATIONS FOR BRILINTA
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.
Patients can find out more information about BRILINTA
at www.BRILINTA.com or by calling 1-888-412-7454.
Please read full Prescribing Information,
including Boxed WARNINGS, and Medication
Guide.
You are encouraged to report negative side effects of
prescription drugs to the FDA.
Visit www.fda.gov/safety/medwatch or call
1-800-FDA-1088.
NOTES TO EDITORS
About AstraZeneca in Cardiovascular, Renal & Metabolism
(CVMD)
Cardiovascular, renal and metabolic diseases together form one
of AstraZeneca’s main therapy areas and platforms for future
growth. By following the science to understand more clearly the
underlying links between the heart, kidney 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 even
regenerate organs and restore function, by continuing to deliver
transformative science that improves treatment practices and
cardiovascular 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. The Company also is selectively active
in the areas of autoimmunity, neuroscience and infection.
AstraZeneca operates in over 100 countries and its innovative
medicines are used by millions of patients worldwide. For more
information, please visit http://www.astrazeneca-us.com and follow
us on Twitter @AstraZenecaUS.
References
1. World Health Organization. Cardiovascular Disease:
World Heart Day 2017 Accessed October 29, 2018.
http://www.who.int/cardiovascular_diseases/world-heart-day-2017/en/.
2. Wang H et al. Global, regional, and national life expectancy,
all-cause mortality, and cause-specific mortality for 249 causes of
death, 1980–2015: A systematic analysis for the Global Burden of
Disease Study 2015. The Lancet 2016; 388(10053):1459–544.
https://doi.org/10.1016/S0140-6736(16)31012-1.
3. Ogurtsova K et al. IDF Diabetes Atlas: Global estimates for
the prevalence of diabetes for 2015 and 2040. Diabetes Res Clin
Pract 2017; 128:40–50. https://doi.org/10.1016/j.diabres.2017.03.024.
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