to triple the risk that nonusers did.
Most cases of C. difficile, which can
cause severe diarrhea, erupt in hospitals.
PPIs lower stomach acidity, allowing
C. difficile in the gut to survive when it
wouldn’t otherwise, Howell says. The
microbes travel downstream, where they
release toxins that cause the diarrhea.
Other microbes may survive as well,
possibly causing pneumonia if they get
splashed up into the esophagus and
breathed into the lungs. A separate study
by Howell’s team showed a link between
hospital-acquired pneumonia and PPI
use, with the drugs raising the odds of
infection by 10 to 40 percent.
Less certain but also raising concern
is whether PPIs interfere with B12 vitamin levels and with the activity of some
drugs. Early reports suggested problems
with PPI use and a particular anticlot-ting medication called clopidogrel, or
Plavix, but more recent data have cast
doubt on that link.
Too many ’scripts
Not everyone agrees that the risks are
as worrisome as these studies suggest.
David Johnson, a gastroenterologist at
Eastern Virginia Medical School in Norfolk, says that some other studies haven’t
found any risk from PPI use, and that
many studies fail to take into account the
risk run by a patient who stops taking a
PPI. “If you only look at one side, it’s not
a balanced assessment,” Johnson says.
He also questions why people with
pernicious anemia, who make very little
stomach acid, aren’t beset by C. difficile
infections or pneumonia. “And their
bones should just crumble,” he says, if
acid suppression is deleterious. “It just
doesn’t make sense.”
The absolute risk of the medical problems linked to use of PPIs — the likelihood
that a given individual will encounter
one — is small. In the study by Metz and
his colleagues, for example, it works out
to four broken hips per 1,000 people
using PPIs for more than a year. That’s up
from two per 1,000 nonusers, calculates
Hye-Kyung Jung of Ewha Womans University in Seoul, South Korea.
“But we ended up giving PPIs to
everybody,” counters Howell,
and that multiplies the population at risk. There were
119.4 million prescriptions for
PPIs dispensed in 2009 in the
United States, according to IMS
Health, a Norwalk, Conn.–based
research firm. And that doesn’t
include over-the-counter sales.
Hospital prescribing of acid
neutralizers started in the 1970s
when doctors realized that the
practice could prevent the
stress-induced bleeding ulcers
that plague patients in intensive
care units and are exacerbated
by stomach acid. (Easing the
symptoms of stomach ulcers is
considered a valid medical use
of PPIs today.)
A Canadian study in 1994
had shown that such stomach
bleeding was rare in hospitalized patients who didn’t have
respiratory failure or a defect
in the blood’s clotting ability.
But six years later, Yale University scientists reported that many patients at
low risk of developing a stomach bleed
were being placed on PPIs or other acid-blockers anyway.
Research done at the University of
Michigan Hospital revealed that most
acid-suppressing drug prescriptions
doled out by the hospital’s doctors were
inappropriate — the patients didn’t have
acid reflux and weren’t at risk of stomach
bleeding. And a 2006 study from New
Zealand found that four in 10 hospital
patients were on PPIs inappropriately.
What’s more, people are often sent home
from the hospital with a prescription for
a PPI, and they fill it. “A lot of people just
go on the medication they are prescribed
and don’t ask questions,” says Regal.
sources: saad et Al/Int. J. of ClIn. PrACtICe
2005; grant et Al/PhArMACy World & SCIenCe
2006; batuwitage et Al/PoStgrAd. Med. J. 2007;
pham et Al/AnnAlS of PhArMACotherAPy 2006
on ppis with valid medical reason
on ppis with no valid medical reason
Global overprescribing Four
hospital-based studies highlight the
common practice of prescribing ppis
to patients even when the patients
don’t need the heartburn drugs.
28 days. By standard scoring of
stomach distress, both groups
started with very little heartburn. One week after treatment
ended, however, stomach distress rose dramatically in those
who had been on PPIs but not
in the others. And 11 of the 25
on PPIs complained of stomach
problems afterward, compared
with only two of 23 on a placebo.
“The stomach tries to compensate for the decrease in acid
secretion that PPI medication
leads to,” says Niklasson. “So
when patients stop their PPIs,
Despite these reports, pharmaceutical
firms continue to promote PPIs actively.
Internist Mitchell Katz, director of public health for the city of San Francisco,
says the drugs are being marketed to
young adults. He cites a commercial on
the Internet that shows young people
going out on the town, discussing taking
a PPI in anticipation of possible heartburn later. “I think PPIs have become
more of a lifestyle drug. People don’t
really understand the risks,” Katz says.
PPIs continue to be the best drug for
acid reflux. “Many people will need to
take them,” says researcher Shelly Gray
of the University of Washington in Seattle. “But some people take PPIs who could
manage with changes in lifestyle or with
a less potent heartburn medication.” s
On the rebound
Giving people PPIs when they don’t need
them may result in PPI rebound, Swedish scientists report. Pharmacist Anna
Niklasson and colleagues at the University of Gothenburg randomly assigned
48 healthy volunteers without acid reflux
to receive either a PPI or a placebo for
s m. katz. “Failing the acid test.” Archives
of Internal Medicine. may 10, 2010.