1 / 53

Successful Strategies for Managing Acid-Related Disease in Primary Care

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.

Solomon
Télécharger la présentation

Successful Strategies for Managing Acid-Related Disease in Primary Care

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. Content is provided to you AS IS for your information and personal use only. Download presentation by click this link. While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server. During download, if you can't get a presentation, the file might be deleted by the publisher.

E N D

Presentation Transcript

  1. 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

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

  3. ? 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!

  4. 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.

  5. ? 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!

  6. Extraesophageal GERD Esophagitis Nonerosive GERD (EGD negative) ENT Bleeding Stricture Asthma Impairs Quality of Life Barrett’s Metaplasia and Adenocarcinoma Dental 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

  7. GERD Severity ≈ Pathophysiologic Determinants of Esophagitis Severity and Chronicity Aggressive Factors Causticity of gastric juice N of reflux events • 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 Acid clearance Tissue resistance  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.

  8. Traditional Assumptions Concerning GERD Natural History Spectrum/Progression Mild Reflux: NERD 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.

  9. Evolving GERD “Phenotypic Model” Progression Within the Group NERD ErosiveEsophagitis Barrett’sEsophagus 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.

  10. 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.

  11. 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.

  12. 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.

  13. ? 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!

  14. 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.

  15. GERD Symptom Profile on Presentation in Primary Care Jones R, et al. Scand J Gastroenterol Suppl. 1995;211:35-38.

  16. 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.

  17. 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.

  18. 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.

  19. Additional GERD Diagnostic Techniques • 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.

  20. ? 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!

  21. Focus of Medical Management of GERD—Compensatory, Not Curative It’s all about acid! • PPIs • H2RAs • Antacids H2RAs =histamine2-receptor antagonists.

  22. Meta-Analysis of PPIs, H2RAs, and Placebo for Healing Erosive Esophagitis (n) = Number of studies 100 (2) (3) PPIs (26) 80 (27) (4) (22) H2RAs 60 (25) Total Healed (%) (25) (23) 40 (9) (2) Placebo (5) (8) (5) 20 0 2 4 6 8 12 Therapy (weeks) Chiba N, et al. Gastroenterology. 1997;112:1798-1810.

  23. Omeprazole 20 mg (N = 1575) 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) 0.75 1.0 1.25 1.5 1.75 2.0 Favors PPI Favors H2RA CI = confidence interval.Caro JJ, et al. Clin Ther. 2001;23:998-1017.

  24. PPI Therapy Is Extremely Effective in the Majority of Patients With GERD—Comparison Studies Versus Omeprazole 100 85%-95% 80 Omeprazole Lansoprazole 60 Pantoprazole Patients With Healed Erosive Esophagitis (%) 40 Rabeprazole Esomeprazole 20 0 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.

  25. Comparison of Maintenance Therapies for Erosive Esophagitis PPI Healing Dose PPI Maintenance Dose H2RA 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.

  26. Continuous Versus On-Demand PPI Therapy—Maintaining Esophagitis Healing Esomeprazole 20 mg QD (n = 241) Harder to maintain healing with more severe esophagitis Esomeprazole 20 mg on demand (n = 229) 100 93 90 90 90 81 80 78 80 70 65 58 60 Patients in Endoscopic Remission at 6 Months (%) 51 50 44 40 30 20 10 0 A B C D All patients P <.0001 Stratified According to Baseline Los Angeles Grade Sjostedt S, et al. Aliment Pharmacol Ther. 2005;22:183-191.

  27. Esomeprazole 20 mg QD Esomeprazole 40 mg QD Lansoprazole 15 mg QD Placebo 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.

  28. ? 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!

  29. What Is a PPI Failure? • 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

  30. + + + Los Angeles A-D Esophagitis – NERD – • NERD (hypersensitive) • Weakly acidic reflux – Functional Heartburn GERD: Esophagitis, NERD, or Functional Heartburn? Endoscopy GERDSymptoms? MII/pH Monitoring Excess Esophageal Acid Exposure MII/pH Monitoring Symptom Correlation MII = multichannel intraluminal impedance.

  31. Abnormal pH Monitoring in Symptomatic Patients Taking PPIs 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.

  32. EMD • 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

  33. No Reflux • Functional • Not uniquely chemosensitive • Not uniquely mechanosensitive Nonerosive Reflux Disease Abnormal Reflux Non–acid mediated Acid mediated

  34. Reflux Treatment in 2007Summary • 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

  35. ? 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.

  36. Burden of NSAIDs • 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.

  37. Aspirin Alone or With Another NSAID: Risk of Upper GI Complications 8 7 6 5 Relative Risk of Upper GI Complications 4 3 2 1 0 Aspirin75 mgQD Aspirin150 mgQD Aspirin300 mgQD NSAIDs Aspirin + OtherNSAIDs Weil J, et al. BMJ. 1995;310:827-830.

  38. 13.5 Past Complicated Ulcer 9 Multiple NSAIDs* 7 High-Dose NSAIDs 6.4 Anticoagulant 6.1 Past Uncomplicated Ulcer 5.5 Age >60 Years 2.2 Steroids 0 5 10 15 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.

  39. A Practical Guide to NSAID Therapy CV = cardiovascular. *Ibuprofen should be used with caution in individuals taking aspirin. Fendrick AM, et al. Am J Manag Care. 2004;10:740-741.

  40. Antisecretory Cotherapy 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.

  41. GI Advisory Committee Consensus on 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.

  42. Case Study

  43. Case Study: Presentation • 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

  44. Case Study: Medical and 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

  45. ? 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!

  46. ? 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!

  47. Q & A

  48. PCE Takeaways

  49. PCE Takeaways • 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

  50. PCE Takeaways • 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

More Related