467
POOR ADHERENCE TO RECOMMENDATIONS TO PREVENT
GASTROINTESTINAL BLEEDING AMONG ANTICOAGULATION CLINIC
PATIENTS
Jacob E. Kurlander, Xiaokui Gu, James M. Scheiman, Brian Haymart, Eva Kline-Rogers,
Sameer Saini, Scott Kaatz, Steve Almany, Michael McNamara, Jay Kozlowski, James
Froehlich, Geoffrey Barnes
Background: Guidelines recommend that patients at high risk for upper gastrointestinal
(GI) bleeding take a proton pump inhibitor (PPI) for prevention. Objectives: To evaluate
levels of guideline-adherent PPI prescription in a network of anticoagulation clinics. We
hypothesized that guideline adherence would be no better than historical levels among high-
risk NSAID and aspirin users. Patients/Methods: Retrospective database review of new
warfarin-treated patients in a consortium of six anticoagulation clinics from 2011-16. Patients
on combined warfarin + antiplatelet therapy were considered high risk for upper GI bleeding
and therefore to have an indication for PPI prophylaxis. Patient medications and comorbidities
were used to develop a multivariable logistic regression model for PPI prescription. Results:
The sample included 5,296 patients, 45.1% of whom were considered high risk for GI
bleeding because of concurrent aspirin use (39.2%). 34.4% of high-risk patients were on
PPI while 29.9% of patients not at high risk were on PPI. In multivariable logistic regression,
age (OR 1.09 per 10 years, 95% CI 1.05-1.14), male gender (OR 0.86, 95% CI 0.77-0.97),
prior GI bleed (OR 2.81, 95% CI 2.17-3.63), any anti-platelet agent (OR 1.20, 95% CI
1.06-1.36), glucocorticoid (OR 2.39, 95% CI 1.94-2.94), and SSRI (OR 1.79, 95% CI 1.48-
2.16) were associated with PPI prescription. Conclusions: In a multi-system network of
anticoagulation clinics, a minority of patients who are at high risk for GI bleeding receive
guideline-recommended PPI prophylaxis. Anticoagulation clinics should ensure proper pro-
phylaxis against GI bleeding in this vulnerable population.
468
WHICH PPI, HOW MUCH, HOW OFTEN? A SYSTEMATIC REVIEW OF
DRUGS, DOSAGES, AND REGIMENS
David Y. Graham, Aylin Tansel
Background: Proton pump inhibitors (PPIs) are widely used and compared. It is unclear if
they are interchangeable and how (eg, mg per mg) and whether increasing the dose is
superior to giving multiple doses per day. Aim: To provide a rational basis for PPI use for
different indications such as ulcer healing, treatment of GERD, and as an adjuvant to H.
pylori therapy. Methods: We searched PubMed for clinical trials published from inception
through August 2016 using a combination of MeSH terms and keywords for proton pump
inhibitors, clinical trials and pH. We also manually searched the bibliographies of relevant
articles for references not captured by the search strategy. We included studies if they were
randomized clinical trials that performed pH testing after a minimum of 5 days on solid
dosage forms of proton pump inhibitors. We compared drugs using the biomarker of the
proportion of time over 24 hrs intragastric pH 4 that provides a surrogate marker for
relative potency that compensates for differences in pharmokinetics and pharmodynamics
among the PPIs. We used Kirchheiner et al. (Eur J Clin Pharmacol 2009;65:19) estimates
of relative potencies of different PPIs as omeprazole equivalents (OE), (eg, 40 mg pantopra-
zole, 30 mg lansoprazole, 20 mg omeprazole, 20 mg esomeprazole and 20 mg rabeprazole =
9, 27, 20, 32, and 36 mg OE, respectively). We then calculated linear regression models
for daily, twice daily, and three times daily regimens. Results: Results for proportion of
time with pH 4 by OE are shown in Figure 1 with PPI regimens of once daily (126 study
arms, 4,034 patients), bid (32 study arms, 744 patients), and tid (5 study arms, 106 patients).
Once daily regimens from 9 to 80 mg OE increased the time the intragastric pH was 4
linearly over a relatively narrow range (44 to 59%); increasing the dose to 128 mg OE
produced no further increase. Bid dosing had a more profound effect and also increased
the pH 4 linearly with the lowest OE providing greater benefit than the highest dose of
once daily dosing (eg, b.i.d. dosing of pantoprazole 40 mg [18 OE] pH 4 66%, omeprazole
20 mg 70%, esomeprazole 64 mg daily 87% [128 OE]). T.i.d. dosing did not significantly
produce further improvement in acid suppression when compared with b.i.d. dosing. Con-
clusion: PPIs can be used interchangeably. It is also possible to increase or decrease amount
of acid suppression by changing drugs. Studies claiming superiority of one PPI over another
actually assessed the marked differences in OE (eg, 40 mg pantoprazole [9 mg OE] vs. 40 mg
esomeprazole [64 mg OE]). Functionally, 30 mg lansoprazole or omeprazole are equivalent
to 20 mg of esomeprazole or rabeprazole. Clinically, cost per OE is likely the most important
variable to decide between drugs. More acid suppression can be gained through switching
to bid dosing as opposed to increasing once a day dosing.
S-113
AGA Abstracts
469
CHARACTERISTICS ASSOCIATED WITH DECREASED RELAPSE AFTER
PROTON PUMP INHIBITOR DISCONTINUATION IN PATIENTS WITH
GASTROESOPHAGEAL REFLUX DISEASE
Katherine Cheng, Yao-Wen Cheng
Background: Proton pump inhibitors (PPI) for the treatment of gastroesophageal reflux
disease (GERD) related symptoms is highly successful. However, discontinuation after an
8-week trial is infrequently attempted in the primary care setting. Chronic PPI users have
evidence of increased parietal cell mass and hyper-responsiveness to gastrin stimulation.
After discontinuation of therapy, patients experience rebound acid hypersecretion with
relapse rates as high as 80% after one year. Continued use of PPI therapy leads to unnecessary
costs and increased risk of osteoporotic fracture and enteric infections. More studies are
needed to determine patient characteristics associated with successful PPI discontinuation.
Objective: To describe characteristics associated with successful discontinuation of PPI
therapy in chronic users with gastroesophageal reflux disease. Methods: Patients with a
diagnosis of GERD being treated with chronic daily PPI were retrospectively identified from
06/2016 to 9/2016. Patients were excluded if they had red flag symptoms, indications for
chronic PPI use (eg Barrett's esophagus or Zollinger-Ellison syndrome), concurrent non-
GERD gastrointestinal etiologies, and prior attempts at PPI discontinuation. PPIs were discon-
tinued either abruptly or in a stepwise fashion (histamine-2 receptor antagonist twice daily
for 2 weeks, then daily for 2 weeks, then off). Patients were then followed for up to 3
months for symptom relapse. Chi-square and Student's t-test statistical analysis was utilized.
Results: 37% of patients (46/123) on PPI therapy met eligibility criteria. These patients
were age 5413.7 with Charlson comorbidity score 32.1. 59% were female. Three months
after discontinuing PPI therapy, the relapse rate was 10% (2/19) with tapering therapy versus
37%(10/27) with abrupt discontinuation (p=0.044). The remission group had a significantly
lower body mass index (BMI) compared with the relapse group (27.87.2 vs 44.210.5,
p<0.001). When a tapering regimen was used, the odds ratio for relapse was 0.11 versus
abrupt discontinuation (95% CI 0.013-0.963; p = 0.046). There were no significant differ-
ences in Charlson comorbidity score (p=0.949), cardiac comorbidities (p=0.780), respiratory
comorbidities (p=0.179), active smoking status (p=0.074), age (p=0.330), and gender (p=
0.182) when the relapse and remission groups were compared. Conclusions: Discontinuation
of chronic PPI therapy in patients with GERD is more successful with a tapering regimen
and in patients with lower BMI. Patients with a diagnosis of GERD without red flag symptoms
and endoscopic evidence of mucosal lesions should be considered for discontinuation of
PPI therapy to reduce unnecessary costs and associated complications.
470
AN AMBULATORY PROGRAM TO REDUCE PPI UTILIZATION IN
GASTROESOPHAGEAL REFLUX DISEASE
Amanda B. Siegel, Rajesh N. Keswani, Olga Alexeeva, Gwen Cassidy, David M. Liebovitz,
John E. Pandolfino, Rena Yadlapati
Background: Although most patients with gastroesophageal reflux disease (GERD) tolerate
dose reductions or cessation of proton pump inhibitor (PPI) therapy, patients commonly
remain on PPI therapy indefinitely. Given the major economic burden and concerns of
adverse risks related to long-term PPI use, reducing unnecessary PPI use is a health care
priority. The objectives of this study were to 1) Implement an ambulatory PPI monitoring
program, 2) Taper PPI therapy when appropriate, and 3) Assess impact on PPI utilization.
Methods: We performed a prospective pragmatic implementation study at a single-center
over one year (10/2015-9/2016). Through an automated trigger, the electronic health record
identifies patients with a diagnosis of GERD and prompts providers to enroll patients in a
PPI monitoring program. Patients requiring long-term PPI therapy (e.g., Barrett's esophagus,
Los Angeles B esophagitis or higher) are excluded. As part of the PPI program, the study
team contacts patients by phone to assess PPI use, adherence/appropriate use (taking regularly
30-60 minutes prior to meal), and symptom response 4-6 weeks after enrollment. Non-
adherent patients are counseled on proper PPI use, GERD-specific lifestyle modifications
and alternative treatment options for GERD. Patients with > 50% symptom response and
GerdQ 6 are considered responders. PPI responders are offered PPI reduction through a
structured tapering program along with lifestyle counseling (Figure 1). Follow-up at one-,
three- and six-months is performed to assess PPI use and symptom control. Results: Over
AGA Abstracts