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News
Sept. 18, 2012,
Are Stroke Drugs Better Than Stents?
Medical Device Makers Lobby
Medicare to Widen Coverage but Some Doctors Oppose More Surgeries,
By
THOMAS M. BURTON,
"The great majority of patients won't get
a benefit from stents or surgery," said Australian neurologist Anne L.
Abbott, who has led a pushback against high rates of carotid surgery and
stents. About 125,000 Americans now get carotid surgery or carotid
stents each year.
Her research has concluded that stroke
rates have plummeted in recent years in patients with neck-artery
blockage and no symptoms, largely because of the advent of modern
antiplatelet drugs like Plavix, blood-pressure drugs and cholesterol
medicines. She and other proponents of drug therapy point out that
$21,200 carotid operations and $33,500 carotid-stent placements are
costing the U.S. taxpayer up to eight times what drug treatment would
cost.
August 2012, Personalized
Medicine "The most momentous moment in all of medicine. The
biggest shake up to occur in medical history"
-Eric Topol, MD.
Broadcast: Minnesota Public Radio News
Presents
Three doctors debate the
pros and cons -- and the costs and benefits -- of
high-tech and genomic medicine.
Guests:
Eric
Topol: MD. Cardiologist.
Former head of the Cleveland Clinic, now director of
Scripps Translational Science Institute.
Ezekiel Emanuel: MD.
Oncologist. Chair of medical ethics at the University of
Pennsylvania
Margaret Hamburg: MD.
Internal medicine and neuroscience. Commissioner of the
Food and Drug Administration.
July 2012
Diagnostics
creating ‘niche buster’ drugs, By Andrew Jack in London
“The science is really starting to explode,” agrees Daniel
O’Day, chief operating officer of
Roche’s diagnostics division, who says 60 per cent of the Swiss
pharmaceutical group’s pipeline of experimental drugs are now linked to a
companion diagnostic. While cancer is its core focus, he says
Roche is also studying tests for its experimental treatments for
Alzheimer’s and asthma.
But pharmaceutical companies are nervous about whether
those who buy drugs, such as the NHS in the UK, will pay much higher prices
for those medicines that come with a diagnostic test, helping compensate
drugmakers for far lower sales volumes.
Nor is everyone so bullish. A study last year by Tufts
Center for the Study of Drug Development in Boston concluded that there was
still scepticism over the clinical usefulness of many tests. As
understanding of diseases grow, for instance, the value of identifying a
particular genetic mutation may prove less valuable than originally thought.
But Loic Kubitza, a director with PwC who has tracked a
surge in partnerships between diagnostics and drug companies since 2009,
says: “In the past, there was a lot of hype and not much happening. Recent
years have really confirmed an upswing. There is no way back. This trend is
going to continue.”
2011: The American College of
Cardiology Foundation and the American Heart Association have incorporated
platelet reactivity testing in the 2011 ACCF/AHA Focused Update to the
Guidelines for the Management of Patients with Unstable
Angina/Non-ST-Elevation Myocardial Infarction.
2011: New
recommendations to consider platelet function testing and addressing
modifying treatment: “We know that high on treatment platelet reactivity is
an established risk factor for major cardiac events. With the development of
new, more potent antiplatelet treatment strategies, and the continued
validation of point of care platelet reactivity tests, we as physicians can
utilize platelet reactivity measurements as a tool to ensure we provide our
patients the most appropriate and cost-effective treatment options. This
individualized approach of combining traditional risk factors with an
understanding of the effect of our treatment decisions is something that we
had already implemented at the Cardiovascular Institute.” - Dr. Marco
Valgimigli
2011:
The American College of
Cardiology Foundation/American Heart Association Task Force on Practice
Guidelines
and the Society for Cardiovascular Angiography and Interventions
have incorporated platelet function testing in the 2011 ACCF/AHA/SCAI
Guideline for Percutaneous Coronary Intervention.
2011: New guidelines published by
the Society of Thoracic Surgeons and the Society of Cardiovascular
Anesthesiologists include point-of-care testing for platelet reactivity
testing as a new recommendation for pre-operative patient assessment.
2011 Genetic Platelet Function
Tests:
“…no
link between genotype and cardiovascular events.”
JAMA
meta-analysis and
TheHeart Radio :
Results We retrieved 32 studies of
42 016 patients reporting 3545 CVD events, 579 stent thromboses, and 1413
bleeding events. Six studies were randomized trials (“effect-modification”
design) and the remaining 26 reported individuals exposed to clopidogrel
(“treatment-only” design). In treatment-only analysis, individuals with 1 or
more CYP2C19 alleles associated with lower enzyme activity had
lower levels of active clopidogrel metabolites, less platelet inhibition,
lower risk of bleeding (relative risk [RR], 0.84; 95% CI, 0.75-0.94;
absolute risk reduction of 5-8 events per 1000 individuals), and higher risk
of CVD events (RR, 1.18; 95% CI, 1.09-1.28; absolute risk increase of 8-12
events per 1000 individuals). However, there was evidence of small-study
bias (Harbord test P = .001). When analyses were restricted to
studies with 200 or more events, the point estimate was attenuated (RR,
0.97; 95% CI, 0.86-1.09). In effect-modification studies, CYP2C19
genotype was not associated with modification of the effect of clopidogrel
on CVD end points or bleeding (P .05 for interaction for both).
Other limitations included selective outcome reporting and potential for
genotype misclassification due to problems with the * allele nomenclature
for cytochrome enzymes.
Conclusion Although there was an
association between the CYP2C19 genotype and clopidogrel
responsiveness, overall there was no significant association of genotype
with cardiovascular events.
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Guidelines from professional associations all
recommend different windows for discontinuing
antiplatelet therapy prior to surgery. The
guidelines also offer disparate guidance around
pre-operative testing to determine patients’ level
of platelet inhibition. |
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Guideline
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Date
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Recommendations
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Level of Evidence
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American College of Chest Physicians |
2008 |
Stopping aspirin- or clopidogrel-containing drugs
7–10 days before surgery or a procedure preferred
over stopping them closer to surgery
Routine use of platelet function assays to monitor
the antithrombotic effect of aspirin or clopidogrel
not recommended in patients receiving antiplatelet
therapy
In
patients scheduled for CABG, interrupt clopidogrel
at least 5 days, and preferably, 10 days prior to
surgery |
2C
2C
IC |
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American College of Cardiology Foundation/
American Heart Association |
2011 |
When
the procedure can be delayed, discontinue
thienopyridine in patients scheduled for CABG to
allow the antiplatelet effect to dissipate
Withdraw clopidogrel at least 5 days prior to CABG;
withdraw prasugrel at least 7 days prior to CABG
unless need for revascularization/net benefit of
thienopyridine outweighs risk of excess bleeding
Platelet function testing may be considered if
results may alter management
Genotyping for CYP219 may
be considered if results may alter management |
B
B
C
C
B
C
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Society for Thoracic Surgeons/
Society for Cardiovascular Anesthesiologists/
International Consortium for Evidence Based
Perfusion |
2011 |
Discontinue platelet P2Y12 receptor
inhibitors as soon as 3 days prior to coronary
revascularization
Consider POCT for platelet ADP responsiveness to
identify clopidogrel nonresponders who may not
require a pre-operative waiting period |
IB
IIb
(C) |
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Sources: Ann Thorac Surg 2011;91:944–82; Chest
2008;133:71S–105S; JACC 2011;57:1920–59.
http://www.aacc.org/publications/cln/2011/August/Pages/AntiplateletTherapyandSurgery.aspx#
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2009 Genetic Platelet
Function tests:
NOT
Ready for “Prime
Time”
"First, the genetic
substudy from
CHARISMA
(on which I was a coinvestigator) raised questions about whether this
loss-of-function polymorphism is associated with a worse outcome independent
of the antiplatelet drug(s) a patient is on. Only about half of patients who
have it are hyporesponders to clopidogrel, and
in
almost all examples I am aware of, phenotype trumps genotype.”
-Dr Peter Berger (Geisinger
Health, Danville, PA)
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