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Amanda Jekowsky , American College of
Cardiology, 202-375-6645, ajekowsk@acc.org
November
12, 2008
American College of Cardiology (ACC)/American
College of Gastroenterology (ACG)/American Heart Association
(AHA) Joint Comment on Studies Regarding Possible Interaction
of Clopidogrel and Proton Pump Inhibitors
Two studies released today at the American Heart
Association Scientific Sessions 2008 came to opposite conclusions
in studying whether a class of heartburn drugs called proton
pump inhibitors (PPIs) alter the ability of clopidogrel, an
anti-platelet drug, to prevent cardiovascular events after
stent placement. American College of Cardiology (ACC)/American
Heart Association (AHA) guidelines and statements recommend
dual anti-platelet therapy (aspirin plus a thienopyridine
such as clopidogrel) following stent placement. Previous research
shows that combining a PPI with clopidogrel lessens the risk
of GI bleeding. However, other recent studies have suggested
that adding a PPI could blunt clopidogrel’s anti-platelet
effect. This interaction has not been studied in large numbers
of patients, so there is no definitive evidence that the use
of PPIs will keep clopidogrel from working to prevent cardiac
events.
Neither of the studies presented today provides sufficient
evidence to change clinical practice. In the interest of patient
safety, the AHA/ACC and the American College of Gastroenterology
(ACG) advise that patients who are currently taking these
medications should not change their medication regimen unless
advised by their healthcare provider.
The first study (Abstract # 3998) reviewed major adverse
cardiac events (hospitalization for stroke, heart attack,
angina or bypass surgery) over one year in patients prescribed
clopidogrel after stent placement. The study group included
14,383 patients in the Medco Integrated Database who were
at least 80 percent compliant with refilling their medication.
Patients who took clopidogrel alone were compared with those
taking clopidogrel and PPIs.
The study found that patients receiving both medications
had significantly more major cardiovascular events in a year
than patients taking clopidogrel alone. However, the patients
taking both medications had a higher cardiovascular risk factor
profile (age, gender, diabetes, hypertension, chronic kidney
disease). There are several significant limitations to this
type of study, as acknowledged by the authors. The database
did not include information about participants’ use
of over-the-counter drugs (including aspirin or omeprazole)
and could not account for other cardiovascular risk factors
such as family history, smoking status, blood pressure levels
and lipid values. As the authors themselves concluded, further
investigation should focus on prospective study of this interaction.
The second study (Abstract #3999) reported no adverse effect
of combining a PPI with clopidogrel. CREDO previously found
a benefit of one year vs. one month of treatment with clopidogrel
after coronary stenting. The sub-group analysis reported today
assessed the endpoint of death, MI or stroke in patients on
clopidogrel or placebo with or without a PPI, and showed no
adverse effect of combining a PPI with clopidogrel. Patients
treated with a PPI were at higher baseline risk and had a
worse outcome compared to those who were not, whether they
were given placebo or clopidogrel.
The ongoing COGENT-1 study should help answer some of these
questions – this trial is randomizing patients with
coronary artery disease to ASA plus clopidogrel in combination
with 20 mg of omeprazole (a PPI) or placebo and should provide
further evidence to help address these issues. Other clinical
trials are needed to fully explore this issue.
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The American College of Cardiology is leading the way to optimal
cardiovascular care and disease prevention. The College is
a 36,000-member nonprofit medical society and bestows the
credential Fellow of the American College of Cardiology upon
physicians who meet its stringent qualifications. The College
is a leader in the formulation of health policy, standards
and guidelines, and is a staunch supporter of cardiovascular
research. The ACC provides professional education and operates
national registries for the measurement and improvement of
quality care. More information about the association is available
online at www.acc.org .
The American College of Cardiology (ACC) provides these news
reports of clinical studies published in the Journal of
the American College of Cardiology as a service to physicians,
the media, the public and other interested parties. However,
statements or opinions expressed in these reports reflect
the view of the author(s) and do not represent official policy
of the ACC unless stated so.
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