Successful strategies for managing acid related disease in primary care
1 / 53

- PowerPoint PPT Presentation

  • Updated On :

Successful Strategies for Managing Acid-Related Disease in Primary Care . John E. Pandolfino, MD Assistant Professor of Medicine Feinberg School of Medicine Northwestern University Chicago, Illinois. Faculty Disclosure.

I am the owner, or an agent authorized to act on behalf of the owner, of the copyrighted work described.
Download Presentation

PowerPoint Slideshow about '' - Solomon

An Image/Link below is provided (as is) to download presentation

Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author.While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server.

- - - - - - - - - - - - - - - - - - - - - - - - - - E N D - - - - - - - - - - - - - - - - - - - - - - - - - -
Presentation Transcript
Successful strategies for managing acid related disease in primary care l.jpg

Successful Strategies forManaging Acid-Related Disease in Primary Care

John E. Pandolfino, MD

Assistant Professor of Medicine

Feinberg School of Medicine

Northwestern University

Chicago, Illinois

Faculty disclosure l.jpg
Faculty Disclosure

  • Dr Pandolfino:consultant/speaker/grant support: AstraZeneca; Medtronic, Inc.; Santarus, Inc.

Key question l.jpg


Key Question

In what percentage of your patients with chronic GERD do you consider long-term management strategies?

  • 0%-25%

  • 26%-50%

  • 51%-75%

  • 76%-100%

    Use your keypad to vote now!

Learning objectives l.jpg
Learning Objectives

  • Identify patients at risk for GI complications of acid-related disorders

  • Describe effective strategies for managing GERD

  • Discuss options for minimizing GI risk in patients requiring NSAID therapy

GERD = gastroesophageal reflux disorder; GI = gastrointestinal; NSAID = nonsteroidal inflammatory drug.

Key question5 l.jpg


Key Question

Which of the following increases a person’s

risk of developing esophageal adenocarcinoma?

  • Long-standing GERD symptoms

  • Frequent GERD symptoms

  • Both of the above

  • No study has connected GERD symptom characteristics and adenocarcinoma risk

    Use your keypad to vote now!

G astro e sophageal r eflux d isease l.jpg




Nonerosive GERD

(EGD negative)





Impairs Quality

of Life

Barrett’s Metaplasia




EGD = esophagogastroduodenoscopy; ENT = ear, nose, and throat.

GastroEsophageal Reflux Disease

All individuals exposed to the physical complications from gastroesophageal reflux or who experience clinically significant impairment of health-related well being (quality of life) due to reflux-related symptoms

Genval Working Group 1997

Pathophysiologic determinants of esophagitis severity and chronicity l.jpg



Pathophysiologic Determinants of Esophagitis Severity and Chronicity

Aggressive Factors

Causticity of

gastric juice

N of reflux


  • Chronic condition usually not attributed to excess acid secretion

    • Number of acid reflux events and caustic nature of refluxate are primary determinants of GERD severity

    • Tissue resistance and acid clearance also contribute

  • Treatment approaches are compensatory, rather than curative

  • Therapeutic focus is on refluxate causticity

    • Few existing medical therapies affect the number of reflux events

    • No noninvasive therapies to correct GERD-associated anatomical and motor abnormalities

Defensive Factors





Barlow WJ, Orlando RC. Gastroenterology. 2005;128:771-778.

Dent J, et al. Gut. 2005;54:710-717.

DeVault KR, et al. Am J Gastroenterol. 2005;100:190-200.

Kahrilas PJ, et al. In: Gastrointestinal and Liver Disease: Pathophysiology/Diagnosis/Management. 7th ed. Philadelphia, Pa:WB Saunders Co; 2002:599-622.

Traditional assumptions concerning gerd natural history l.jpg
Traditional Assumptions Concerning GERD Natural History


Mild Reflux:


Moderate to Severe Reflux:

Erosive Esophagitis

Severe Reflux:

Barrett’s Esophagus

NERD = nonerosive reflux disease.Adapted from Fass R, Ofman JJ. Am J Gastroenterol. 2002;97:1901-1909.

Evolving gerd phenotypic model l.jpg
Evolving GERD “Phenotypic Model”

Progression Within the Group




Typical and Atypical Symptoms

StrictureUlcerGI Bleeding

Adenocarcinomaof the Esophagus

Fass R, Ofman JJ. Am J Gastroenterol. 2002;97:1901-1909.

Pandolfino JE, Shah N. Dig Liver Dis. 2006;38:648-651.

Association between gerd symptom frequency and duration l.jpg
Association Between GERD Symptom Frequency and Duration

N = 1438 (n =189 with esophageal adenocarcinoma).

Lagergren J, et al. N Engl J Med. 1999;340:825-831.

Summary of disease progression importance of early treatment l.jpg
Summary of Disease ProgressionImportance of Early Treatment

  • NERD patients may develop esophagitis on follow-up

    • However, usually mild esophagitis

  • Esophagitis may heal in patients who continue to have symptoms on PPI therapy

  • Left untreated, esophagitis may progress to worse complications, including esophageal ulcer and stricture

  • Long-standing and frequent GERD symptoms have been shown to increase the risk of esophageal adenocarcinoma

PPI = proton pump inhibitor.

Fass R, Ofman JJ. Am J Gastroenterol. 2002;97:1901-1909.

Lagergren J, et al. N Engl J Med. 1999;340:825-831.

Summary of disease progression barrett s esophagus l.jpg
Summary of Disease ProgressionBarrett’s Esophagus

  • Barrett’s esophagus can develop after years of reflux disease

    • However, usually diagnosed on initial endoscopy

    • Once developed, typically remains despite antireflux therapy

  • Barrett’s may progress to esophageal adenocarcinoma

    • However, sizeable proportion of adenocarcinoma diagnoses are made without evidence of Barrett’s

Fass R, Ofman JJ. Am J Gastroenterol. 2002;97:1901-1909.

Key question13 l.jpg


Key Question

Approximately what percentage of patients presenting to general practices with GERD symptoms have normal mucosa or erythema only on endoscopy?

  • 75%

  • 55%

  • 35%

  • 15%

    Use your keypad to vote now!

Gerd endoscopic findings in general practice l.jpg
GERD: Endoscopic Findings in General Practice

Percent of patients with:

N = 789 patients with GERD.

Jones R, et al. Scand J Gastroenterol Suppl. 1995;211:35-38.

Gerd symptom profile on presentation in primary care l.jpg
GERD Symptom Profile on Presentation in Primary Care

Jones R, et al. Scand J Gastroenterol Suppl. 1995;211:35-38.

When is empiric therapy appropriate l.jpg
When Is Empiric Therapy Appropriate?

  • 2005 ACG Practice Guidelines: “If the patient’s history is typical for uncomplicated GERD, an initial trial of empirical therapy…is appropriate.”

  • Rationale:

    • Classic reflux symptoms (ie, heartburn, regurgitation) have a positive predictive value of >80% for GERD

    • Regardless of endoscopic findings (erosive vs nonerosive), most patients with typical symptoms are treated with PPIs

  • Further diagnostic testing should be considered if:

    • The patient has alarm symptoms

    • There is no response to empiric therapy

    • The patient has symptoms of sufficient duration to put him/her at risk for Barrett’s esophagus

      • Age >50 – Controversial

      • Longstanding heartburn – How long?

DeVault KR, et al. Am J Gastroenterol. 2005;100:190-200.

Warning signs alarm symptoms l.jpg
Warning Signs/Alarm Symptoms

  • Dysphagia

  • Odynophagia

  • Persistent vomiting

  • Anorexia

  • Unintentional weight loss

  • Anemia

  • Fever

  • Gastrointestinal bleeding (occult or overt)

The presence of any of these symptoms indicates the need for further testing

DeVault KR, et al. Am J Gastroenterol. 2005;100:190-200.

Algorithm for diagnostic referral in patients presenting with gerd symptoms l.jpg
Algorithm for Diagnostic Referral in Patients Presenting With GERD Symptoms

History and Physical Examination

Typical Symptoms Only

  • Heartburn

  • Regurgitation

  • Atypical Symptoms

  • Asthma

  • Chronic cough

  • Chronic hoarseness

  • Nausea and vomiting

  • Unexplained chest pain

  • Early Referral Symptoms

  • Dysphagia

  • Early satiety

  • Frequent vomiting

  • GI bleeding

  • Weight loss

Empiric Treatment

Diagnostic Testing

Katz PO. Am J Gastroenterol. 1999;94(11 Suppl):S3-S10.

Additional gerd diagnostic techniques l.jpg
Additional GERD Diagnostic Techniques With GERD Symptoms

  • Additional study needed to determine impact of newer techniques of impedance and tubeless pH monitoring on GERD management

EAE = esophageal acid exposure.

DeVault KR, et al. Am J Gastroenterol. 2005;100:190-200.

Key question20 l.jpg

? With GERD Symptoms

Key Question

What overall percentage of patients with erosive

esophagitis experience healing of erosions with

8 weeks of standard-dose PPI therapy?

  • <75%

  • 75%-84%

  • 85%-94%

  • 95%-100%

    Use your keypad to vote now!

Focus of medical management of gerd compensatory not curative l.jpg
Focus of Medical Management of GERD—Compensatory, Not Curative

It’s all about acid!

  • PPIs

  • H2RAs

  • Antacids

H2RAs =histamine2-receptor antagonists.

Meta analysis of ppis h 2 ras and placebo for healing erosive esophagitis l.jpg
Meta-Analysis of PPIs, H Curative2RAs, and Placebo for Healing Erosive Esophagitis

(n) = Number of studies













Total Healed (%)

















Therapy (weeks)

Chiba N, et al. Gastroenterology. 1997;112:1798-1810.

Meta analysis of ppis versus ranitidine for healing erosive esophagitis l.jpg

Omeprazole 20 mg (N = 1575) Curative

Pantoprazole 40 mg (N = 249)

Meta-Analysis of PPIs Versus Ranitidine for Healing Erosive Esophagitis

Healing Rate Ratio (95% CI) Versus Ranitidine 300 mg

P <.05 for all PPIs vs ranitidine 300 mg

Lansoprazole 30 mg (N = 948)

Rabeprazole 20 mg (N = 338)







Favors PPI

Favors H2RA

CI = confidence interval.Caro JJ, et al. Clin Ther. 2001;23:998-1017.

Slide24 l.jpg
PPI Therapy Is Extremely Effective Curativein the Majority of Patients With GERD—Comparison Studies Versus Omeprazole








Patients With Healed

Erosive Esophagitis (%)






N = 8531

N = 2862

N = 2023

N = 13044*

8 Weeks

*P <.05 versus omeprazole.

1. Castell DO, et al. Am J Gastroenterol. 1996;91:1749-1757.

2. Mössner J, et al. Aliment Pharmacol Ther. 1995;9:321-326.

3. Dekkers C, et al. Aliment Pharmacol Ther. 1999;13:49-57.

4. Kahrilas P, et al. Aliment Pharmacol Ther. 2000;14:1249-1258.

Comparison of maintenance therapies for erosive esophagitis l.jpg
Comparison of Maintenance Therapies for Erosive Esophagitis Curative

PPI Healing Dose

PPI Maintenance Dose


38 randomized, controlled trials

Follow-up time: 24-52 weeks

NNT = 4.7

NNT = 2.9

NNT = number needed to treat.Donnellan C, et al. Cochrane Database Syst Rev. 2004;4.

Continuous versus on demand ppi therapy maintaining esophagitis healing l.jpg
Continuous Versus On-Demand PPI Therapy Curative—Maintaining Esophagitis Healing

Esomeprazole 20 mg QD (n = 241)

Harder to maintain healing with more severe esophagitis

Esomeprazole 20 mg on demand (n = 229)














Patients in Endoscopic Remission at 6 Months (%)













All patients

P <.0001

Stratified According to Baseline Los Angeles Grade

Sjostedt S, et al. Aliment Pharmacol Ther. 2005;22:183-191.

On demand therapy for maintenance of symptom control nonerosive gerd l.jpg

Esomeprazole 20 mg QD Curative

Esomeprazole 40 mg QD

Lansoprazole 15 mg QD


On-Demand Therapy for Maintenance of Symptom Control*—Nonerosive GERD

Rabeprazole 10 mg QD

P <.05 for all PPIs vs placebo in each study

*After an initial acute treatment period with continuous PPI to control symptoms, asymptomatic patients were enrolled in the on-demand period.

Bigard MA, Genestin E. Aliment Pharmacol Ther. 2005;22:635-643.

Bytzer P, et al. Aliment Pharmacol Ther. 2004;20:181-188.

Talley NJ, et al. Eur J Gastroenterol Hepatol. 2002;14:857-863.

Key question28 l.jpg

? Curative

Key Question

What constitutes PPI therapy failure?

  • Failure of the FDA-approved dose

  • Failure of 2  the FDA-approved dose

  • Failure of 2  the FDA-approved dose BID

  • Failure is not defined

    Use your keypad to vote now!

What is a ppi failure l.jpg
What Is a PPI Failure? Curative

  • FDA-approved dose?

  • 2  the FDA-approved dose?

  • FDA-approved dose BID?

  • 2  the FDA-approved dose BID?

I typically continue evaluation after the

patient has failed double-dose treatment

Gerd esophagitis nerd or functional heartburn l.jpg

+ Curative



Los Angeles A-D Esophagitis


  • NERD (hypersensitive)

  • Weakly acidic reflux

Functional Heartburn

GERD: Esophagitis, NERD, or Functional Heartburn?



MII/pH Monitoring

Excess Esophageal Acid Exposure

MII/pH Monitoring

Symptom Correlation

MII = multichannel intraluminal impedance.

Abnormal ph monitoring in symptomatic patients taking ppis l.jpg
Abnormal pH Monitoring in Symptomatic Patients Taking PPIs Curative

250 GERD patients

  • pH testing should only be performed after patients have failed double-dose PPI, if testing on medication

Typical (135)

Extra-esophageal (115)

BID PPI (56)

BID PPI (75)

QD PPI (40)

QD PPI (79)

% time pH <4

0.3 (0%-15%)

0.3 (0%-30%)

1.2 (0%-28%)

0 (0%-4.8%)

# abnormal

4 (7%)

12 (30%)

24 (31%)

1 (1%)

Charbel S, et al. Am J Gastroenterol. 2005;100:283-289.

Potential etiologies of heartburn not all heartburn is gerd l.jpg

  • EMD Curative

  • Eosinophilic esophagitis

  • Functional heartburn

  • Alkaline reflux?

  • Distention

Heartburn not caused by acid reflux

Potential Etiologies of Heartburn—Not All Heartburn Is GERD

  • Esophagitis

  • Histopathologic esophagitis

  • Healed esophagitis

  • Acid-sensitive esophagus

  • Weakly acidic reflux?

Heartburn caused by acid reflux

EMD = esophageal motility disorder

N on e rosive r eflux d isease l.jpg

No Reflux Curative

  • Functional

  • Not uniquely chemosensitive

  • Not uniquely mechanosensitive

Nonerosive Reflux Disease

Abnormal Reflux





Reflux treatment in 2007 summary l.jpg
Reflux Treatment in 2007 CurativeSummary

  • Focus has shifted from esophagitis to symptom control

  • PPIs are the mainstay of therapy

    • Long-term safety is good

    • Minor concerns

      • Osteoporosis

      • Clostridium difficile colitis

  • Refractory or PPI unresponsive GERD requires concern for other etiology

    • Nonacid reflux

    • Functional heartburn

Key question35 l.jpg

? Curative

Key Question

Of the following factors, which places patients

at the highest risk for developing GI

complications/adverse events?

  • Use of multiple NSAIDs (including aspirin)

  • Use of high-dose NSAIDs

  • Use of an anticoagulant

  • Past uncomplicated ulcer

    Use your keypad to vote now!

NSAIDs = nonsteroidal anti-inflammatory drugs.

Burden of nsaids l.jpg
Burden of NSAIDs Curative

  • More than 111 million NSAID/COX-2 inhibitor prescriptions written in 2004

  • 70% of persons aged ≥65 years take NSAIDs at least weekly

    • 60% of these patients take aspirin

    • 34% take NSAIDs daily

Over 100,000 hospitalizations per year due to NSAID-related complications

COX-2 = cyclooxygenase-2.

IMS NPA Plus, 2004 (January 2004-December 2004).

Talley NJ, et al. Dig Dis Sci. 1995;40:1345-1350.

Aspirin alone or with another nsaid risk of upper gi complications l.jpg
Aspirin Alone or With Another NSAID: CurativeRisk of Upper GI Complications





Relative Risk of Upper GI Complications






Aspirin75 mgQD

Aspirin150 mgQD

Aspirin300 mgQD


Aspirin + OtherNSAIDs

Weil J, et al. BMJ. 1995;310:827-830.

Identify individuals with risk factors for adverse events l.jpg

13.5 Curative

Past Complicated Ulcer


Multiple NSAIDs*


High-Dose NSAIDs




Past Uncomplicated Ulcer


Age >60 Years







Identify Individuals With Risk Factors for Adverse Events

  • Use non-NSAID analgesic whenever possible

  • Use the lowest effective NSAID dose

Odds Ratio

*Including aspirin.

Gabriel SE, et al. Ann Intern Med. 1991;115:787-796.

Garcia Rodriguez LA, et al. Lancet. 1994;343:769-772.

A practical guide to nsaid therapy l.jpg
A Practical Guide to NSAID Therapy Curative

CV = cardiovascular.

*Ibuprofen should be used with caution in individuals taking aspirin.

Fendrick AM, et al. Am J Manag Care. 2004;10:740-741.

Antisecretory cotherapy l.jpg
Antisecretory Cotherapy Curative

Lazzaroni M, et al. Dig Liver Dis. 2001;33:S44-S58.

Graham DY, et al. Arch Intern Med. 2002;162:169-175.

Peura DA. Am J Med. 2004;117:63S-71S.

Gi advisory committee consensus on nsaids l.jpg
GI Advisory Committee Consensus Curativeon NSAIDs

  • Recognized the CV effects of 3 COX-2 inhibitors: celecoxib, valdecoxib, and rofecoxib

  • Endorsed NSAID with a PPI over COX-2 inhibitors

    • Naproxen was the NSAID identified as most favorable

    • Be careful with ibuprofen + aspirin

  • Advised against combination therapy with aspirin and COX-2–selective agents

  • Endorsed using a gastroprotective agent in patients requiring aspirin plus an NSAID

US FDA Arthritis Advisory Committee, Drug Safety and Risk Management Advisory Committee, February 16-18, 2005.

Case study l.jpg

Case Study Curative

Case study presentation l.jpg
Case Study: Presentation Curative

  • Caucasian male aged 50 years with a history of heartburn 3 times per week

  • Occasional nocturnal symptoms with regurgitation and mild dysphagia

  • Trouble sleeping and chronic cough

  • Vital signs stable

    • Mild obesity

    • Otherwise normal

Case study medical and treatment history l.jpg
Case Study: Medical Curativeand Treatment History

  • Medical history includes knee replacement surgery, hypertension, hypercholesterolemia, and pulmonary embolism

  • Tried over-the-counter antacids and H2RAs for 4 weeks

    • Mild improvement but still had significant breakthrough symptoms

  • Other medications

    • Ibuprofen for knee pain 600 mg TID PRN

    • Hydrochlorothiazide

    • Potassium chloride

    • Atorvastatin

  • No known drug allergies

Decision point l.jpg

? Curative

Decision Point

How would you manage this patient?

  • 4 weeks of empiric therapy with standard-dose PPI

  • 4 weeks of empiric therapy with PPI BID

  • Switch patient to standard-dose PPI therapy and add OTC H2RA at bedtime

  • Check for Helicobacter pylori infection

    Use your keypad to vote now!

Decision point46 l.jpg

? Curative

Decision Point

Does this patient need any diagnostic testing

and if so which test?

  • No testing needed—just treat

  • H pylori testing needed

  • Refer for endoscopy

  • Upper GI is all that is needed initially

    Use your keypad to vote now!

Slide47 l.jpg

Q & A Curative

Pce takeaways l.jpg

PCE Takeaways Curative

Pce takeaways49 l.jpg
PCE Takeaways Curative

  • If left untreated, GERD can progress to erosive esophagitis, Barrett’s esophagus, and esophageal adenocarcinoma

  • Focus of medical management of GERD is compensatory, not curative

  • 2005 ACG Practice Guidelines recommend initial trial of empiric PPI therapy if the patient’s history is typical for uncomplicated GERD

Pce takeaways50 l.jpg
PCE Takeaways Curative

  • Know when to consider further testing:

    • Alarm symptoms or atypical symptoms

    • No response to empiric therapy

    • The patient has sufficient duration of symptoms to be at risk for Barrett’s esophagus

Pce takeaways51 l.jpg
PCE Takeaways Curative

  • PPIs are very effective for most patients with GERD

  • PPIs are the mainstay of therapy, with good long-term safety

  • If GERD is refractory or PPI unresponsive, look for other etiology

    • Nonacid reflux

    • Functional heartburn

Pce takeaways nsaids l.jpg
PCE Takeaways: NSAIDS Curative

  • 15% to 30% of regular NSAID users develop ulcers, and potentially fatal complications such as GI bleeding, perforation, or obstruction occur in 1% to 2%

  • Consider antisecretory cotherapy in patients

    • With history of ulcer

    • Taking multiple NSAIDs, including aspirin

    • Taking high-dose NSAIDs

    • Taking an anticoagulant

    • Aged >60 years

Key question53 l.jpg

? Curative

Key Question

In what percentage of your patients with chronicGERD will you likely initiate long-term management protocols?

  • 0%-25%

  • 26%-50%

  • 51%-75%

  • 76%-100%

    Use your keypad to vote now!