Heartburn Drugs
Increase Cardiac Events for Stent Patients by 50%
Proton Pump Inhibitors (PPI)
Seen to Interfere with Anti-Clotting Drug
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May 6, 2009
-- Las Vegas --
Most stent patients are required to take the antiplatelet drug
clopidogrel (Plavix) for at least a year to prevent blood clots
inside
the stent.
A new study, presented today at the Society for Cardiovascular
Angiography and Interventions (SCAI) 32nd Annual Scientific Sessions,
showed that the beneficial effects of Plavix are compromised
by common
drugs, used for the
treatment
of heartburn
and ulcers: the combined risk of hospitalization for heart
attack, stroke and
other serious
cardiovascular illnesses was increased by 50%. |
The study, titled "A National Study
of the Effect of Individual Proton Pump Inhibitors on Cardiovascular
Outcomes
in Patients Treated with Clopidogrel Following Coronary Stenting:
The Clopidogrel Medco Outcomes Study" specifically focused on the
effects of proton pump inhibitors (PPI) omeprazole (Prilosec),
esomeprazole
(Nexium), pantoprazole (Protonix), and lansoprazole (Prevacid), which
together accounted for about 96% of PPI use in the study.
Patients
who receive a drug-eluting stent benefit from taking anti-clotting
medications, including thienopyridines
(such as clopidogrel or ticlopidine) and aspirin, for at least
one year following
the procedure. However, physicians often also prescribe PPIs to
patients taking clopidogrel because of pre-existing stomach disease
or to
reduce
the risk of common side effects such as nausea and gastroesophageal
reflux
(heartburn). Before clopidogrel can exert its anti-clotting effects,
it must be converted from its inactive, pro-drug form to an active
drug by enzymes in the liver. PPIs -- the sixth most commonly
prescribed drug class in the U.S.—can
interfere with those liver enzymes, according to the study.
“Given the large number of patients who undergo
coronary stent procedures each year, and the recommended and wide use
of clopidogrel following this procedure, our findings have implications
for many thousands of patients across the United States,” said Eric
J. Stanek, PharmD, senior director of research, personalized medicine
research and development, Medco Health Solutions, Franklin Lakes, NJ,
and the study’s principal investigator. “Clopidogrel
should continue to be taken as prescribed, and the need for PPI therapy
should be carefully evaluated to ensure that it is prescribed only
when clearly indicated.”
The need to keep taking clopidogrel, as prescribed, and not to stop
prematurely, was emphasized in comments by Dr. Stanek and Dr. Steven
R. Bailey
of
the SCAI. The
risk of stopping clopidogrel is much greater than the potential risks
of taking PPIs. Dr. Bailey emphasized that the results of this study
confirm concerns that have been discussed for some time, and that
no emergency action is needed -- but that patients should discuss
these issues with their cardiologists.
For the study, researchers analyzed integrated data on pharmacy and medical claims from more than 10 million patients, including 16,690 patients taking clopidogrel for a full year following coronary stenting. Of these, 41% also took a PPI, on average, for more than nine months of the year. Over that 12-month period when patients took clopidogrel, investigators evaluated the risk of hospitalization for major adverse cardiovascular events (MACE), which they defined as a combination of heart attack, unstable angina, stroke or temporary stroke-like symptoms, repeat coronary procedures, or cardiovascular death.
The overall MACE risk was 51% higher
among patients taking any PPI. This composite risk was comprised
of a 70% increase in the risk of heart attack or
unstable angina, a
48%
increase
in
the risk of stroke or stroke-like symptom and a 35% increase in
the need for a repeat coronary procedure The findings were equally
concerning when the effects of individual PPIs were
analyzed.
Omeprazole
correlated
with a 39% increased risk of MACE, esomeprazole to a 57% increased
risk, pantoprazole to a 61% increased risk and lansoprazole to
a 39% increased risk. All of the associations were highly statistically
significant. Interestingly enough, the incidence of hospitalization
for upper gastrointestinal bleeding was very small overall: only
1.1% among patients taking
a
PPI and 0.07% among those not taking a PPI.
The Society for Cardiovascular
Angiography and Interventions issued a statement reagrding the
results of the study:
"SCAI believes more research is needed on
this topic. However, given the thousands of patients who receive
stents each year, coupled with
the significant risks demonstrated in this study, SCAI recommends
the use of alternative medications for GI symptoms in patients
with stents when appropriate. Other effective treatments for
heartburn and ulcers include histaminergic (H2) blockers (Zantac,
Tagamet)
or antacids. In some patients the use of PPIs may still be warranted
based on the patient’s medical problems and should be taken
at the direction of the patient’s cardiologist, gastroenterologist
or primary physician.
"Importantly, patients should never stop taking
any prescribed medication without first discussing with their
doctor. Guidelines authored by
SCAI and other cardiovascular organizations recommend dual-antiplatelet
therapy for no less than one year following stent implantation.
Clinical trials have shown this drug regimen effectively prevents
blood clots
that can lead to rare but potentially life-threatening cardiac
events."
Additional
research is needed to determine whether newer, less widely used
PPIs such
as
rabeprazole
(Aciphex)
and dexlansoprazole (Kapidex) are also associated with increased
cardiovascular risk in patients taking clopidogrel. Researchers
are also interested in examining how genetic variations in
the liver enzymes that activate clopidogrel might alter the impact
of PPIs on clopidogrel effectiveness, the potential influence
of the timing of PPI administration, the effect of alternate
dosing
of clopidogrel, and the comparative effectiveness of other
anti-clotting medications.
This study was supported independently by Medco
Health Solutions, Inc, and conducted in collaboration with investigators
from the Indiana University School of Medicine.
Source: Society
for Cardiovascular Angiography and Interventions (SCAI) with additional reporting
by Burt Cohen, May 6, 2009
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