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OBJECTIVES: A considerable proportion of the medication budget of Dutch general practitioners is spent on prescribed long-term acid suppressant drugs. We investigated the magnitude of long-term prescription of acid suppressant drugs in general practice and the frequency and means of confirming the primary working diagnosis.
STUDY DESIGN: We used a retrospective descriptive study of 24 general practices in the Amsterdam region.
POPULATION: We identified those receiving long-term acid suppressant therapy (12 or more weeks/year) from a total of 46,813 patients by extracting data from pharmacy databases.
OUTCOMES MEASURED: We measured the amount and duration of prescriptions for each medication, indications for prescription, and investigations performed by general practitioners.
RESULTS: Of the 46,813 patients, 922 (2%) received long-term acid suppressant therapy. The duration of prescription varied from 12 weeks in 8% of patients to > 52 weeks in 23% of patients (mean = 33 weeks). In 25% of patients, no investigations were performed; 75% of patients underwent endoscopy or ingested a barium meal. The predominant diagnoses in investigated patients were ulcer disease (39%), gastroesophageal reflux disease (49%), and functional dyspepsia (gastritis, normal aspect; 18%). Helicobacter pylori status was available in 29% of patients with ulcer disease. Eradication therapy was reported in 44% of these patients.
CONCLUSIONS: Among patients of physicians in general practice in the Amsterdam region, 2% used long-term acid suppressants. Patients with ulcer disease may stop taking acid suppressants after apparent successful H pylori eradication. Tapering strategies must be developed for patients with mild reflux disease or functional dyspepsia.
- In Dutch general practice, 2% of patients take long-term acid suppressant drugs.
- One third of patients taking long-term acid suppressant drugs have peptic ulcer disease and may not need medication as soon as Helicobacter pylori has been eradicated.
- One fourth of patients taking long-term acid suppressant drugs have never undergone endoscopy or barium study.
- Because patients often do not tolerate sudden cessation of chronic acid suppressant drug use, tapering strategies must be developed.
The average Dutch general practice includes approximately 2350 patients. Of these, 2 to 3 per week, on average, visit their general practitioner (GP) with a complaint of dyspepsia.1 According to the guidelines of the Dutch College of General Practitioners, the treatment of dyspepsia is directed toward symptom relief, usually on an empirical basis, except for patients with symptoms such as sudden weight loss or hematemesis that suggest cancer; these are referred for endoscopy.2 Medication is prescribed in a stepwise fashion from less potent antacids and prokinetics to the more potent H2-blockers and proton pump inhibitors. During our study, long-term treatment with acid suppressant drugs (ASDs) was indicated only for relapsing ulcers or ulcerlike complaints, relapsing esophagitis, and relapsing gastroesophageal refluxlike symptoms.2
ASDs are responsible for a disproportionate share of the medication budget of Dutch GPs because of their high cost, their high frequency of prescription, and their use on a long-term basis.3 We therefore wondered whether the indication for prescribing an ASD was always appropriate. The aim of our study was to describe how commonly ASDs are prescribed and to describe the initial working diagnosis, the diagnostic tests performed to confirm the working hypothesis, and the final diagnosis for each patient.
Methods
Patients
We retrospectively collected data from 24 general practices in Amsterdam from September 1994 to August 1995 on patients taking long-term ASDs (12 or more weeks during the previous year). ASDs included antacids, mucosa-protective agents, prokinetics, H2-blockers, and proton pump inhibitors.4
Patients were identified from a medication database obtained from all cooperating pharmacists that included patient demographics; type, dose, and duration of medications; and use of possible risk-bearing comedications (aspirin, nonsteroidal anti-inflammatory drugs, or prednisone for more than 6 weeks during the study year). In this way we were able to identify almost all patients from the participating general practices who received long-term treatment with ASDs.
Confirmation of gastrointestinal diagnosis
In the Netherlands, a GP receives all available medical information on his patients (ie, letters from specialists, results from any examinations performed) and stores this information in the patient’s medical history file. When a patient switches to another GP, the entire medical history is sent to this new physician. Our principal investigator used these medical history files to determine the diagnosis and reason for the ASD prescription and the diagnostic tests (including Helicobacter pylori investigations) that were ordered to confirm the working diagnosis. Gastroscopy or barium meal radiography at any time during a patient’s life was considered the investigation for confirmation of the diagnosis. If the prescription started after this investigation or as a consequence of it, the investigation was considered the reason for initiating the current long-term treatment. Verification and completion of the obtained data took place in a face-to-face evaluation between the principal investigator and the GP, ensuring the completeness and reliability of the data.
Analysis and statistics
Patients were categorized into group I (investigations to confirm a working diagnosis were performed) and group NI (no investigations were performed). Three subgroups were identified within group I. We included all patients with a duodenal, gastric, or unspecified ulcer in group I-ULCER; group I-GERD included all patients with symptomatic or erosive gastroesophageal reflux disease (GERD); and group I-FUNCTIONAL included patients with only gastritis or with no imaging abnormalities. Patients with an ulcer and esophagitis were placed in group I-ULCER for their patient characteristics and medication prescription and in both groups I-ULCER and I-GERD for their medication indication, diagnostic tests, and eradication of H pylori.
Data were analyzed with the use of Statistical Package for the Social Sciences software (version 7.5.3). The chi-square test was used for comparison of proportions. Significance was set at = .05 (two sided).
Results
General characteristics and medication prescription
Of 46,813 patients listed with the 24 general practices, 988 (2.1%) were identified as long-term users of ASDs. Of these 988 patients, 66 were excluded because of ASD use for gastric or esophageal cancer, nongastric-related indications such as renal failure, or discontinuation of visits to the GP (patient moved or was a temporary visitor). The demographic and prescription characteristics of the remaining 922 patients are presented in Table 1. All patients had used H2-blockers and proton pump inhibitors for 12 weeks or more during the previous year.
Group I-ULCER consisted of 271 ulcer patients; group I-GERD, of 294 patients with reflux disease; and group I-FUNCTIONAL, of 127 patients with functional dyspepsia. Group NI consisted of 230 patients who did not undergo any confirmatory diagnostic testing (no endoscopy or barium study). Among the long-term users, treatment was more frequently prescribed for women than men (55% vs 45%, respectively; P < .05). Women were more likely not to undergo any diagnostic investigation (28% vs 21%, P < .05). If investigated, however, women were less likely than men have an ulcer (30% vs 50%, P < .05) and more likely to have functional dyspepsia (25% vs 11%, P < .05).
Overall, ranitidine was the drug most commonly prescribed. The mean duration of prescription was 33 weeks in the year of study, with a high of 38 weeks in group I-GERD. Almost one fourth of all patients (23%) had been using these drugs for more than 1 year. In more than half of all patients (53%), the medication was prescribed for 1 episode; in the other 47%, medication was prescribed for 2 or more episodes (ie, intermittent prescription). During the study period, 154 patients (17%) had used potential risk-bearing comedication for more than 6 weeks, including 48 with ulcer.
TABLE 1
CHARACTERISTICS AND PRESCRIPTIONS IN 922 PATIENTS (%) WITH LONG-TERM ACID SUPPRESSANT DRUG PRESCRIPTION IN 24 GENERAL PRACTICES IN THE REGION OF AMSTERDAM, THE NETHERLANDS
| DIAGNOSIS AFTER INVESTIGATION | |||||
|---|---|---|---|---|---|
| Characteristics | Total (N=922) | I-ULCER (n = 271) | I-GERD (n = 294) | I-FUNCTIONAL (n = 127) | NI: Stomach Complaints Without Investigation (n = 230) |
| Patients | |||||
| Female | 511 (55) | 41% | 57% | 72% | 62% |
| 15–44 years | 169 (18) | 11% | 17% | 25% | 25% |
| Mean age, years | 61 | 63 | 63 | 57 | 59 |
| Medication, No. | |||||
| Ranitidine | 442 (48) | 141 (52) | 115 (39) | 70 (55) | 116 (50) |
| Cimetidine | 236 (26) | 82 (30) | 48 (16) | 39 (31) | 67 (29) |
| Omeprazole | 241 (26) | 63 (23) | 130 (44) | 22 (17) | 26 (11) |
| Famotidine | 43 (5) | 16 (6) | 15 (5) | 4 (3) | 8 (3) |
| Lansoprazole | 13 (1) | 3 (1) | 5 (2) | 5 (4) | 0 (0) |
| Prescription Time | |||||
| 12–19 weeks | 231 (25) | 67 (25) | 44 (15) | 44 (35) | 76 (33) |
| 20–29 weeks | 184 (20) | 56 (21) | 46 (16) | 27 (21) | 55 (24) |
| 30–39 weeks | 148 (16) | 40 (15) | 50 (17) | 22 (17) | 36 (16) |
| 40–51 weeks | 143 (16) | 44 (16) | 60 (20) | 15 (12) | 24 (10) |
| >52 weeks | 216 (23) | 64 (24) | 94 (32) | 19 (15) | 39 (17) |
| Mean, weeks | 33 | 34 | 38 | 29 | 29 |
| No. of Episodes of Prescription | |||||
| 1 | 485 (53) | 144 (53) | 179 (61) | 51 (40) | 111 (48) |
| 2 | 271 (29) | 78 (29) | 81 (28) | 48 (38) | 64 (28) |
| > 2 | 166 (18) | 49 (18) | 34 (12) | 28 (22) | 55 (24) |
| Group I-ULCER includes all patients with a duodenal, -gastric, or nonspecified ulcer; group I-GERD includes all patients with symptomatic or erosive gastroesophageal reflux disease; group I-FUNCTIONAL includes patients with gastritis or with normal aspect on endoscopy or barium meal. | |||||
| *Total equals more than 100% because of different types of medication per patient; rarely prescribed medications are not mentioned. | |||||
Confirmation of working diagnosis
In 692 of the 922 (75%) patients a diagnostic test was performed to confirm the primary working diagnosis. In 519 (75%), a gastroscopy was performed and in 138 (20%) a barium meal radiograph was taken. In 35 patients, the specific form of investigation was unclear.
The specific diagnoses of the subgroups are shown in Table 2. In patients with ulcer, use of NSAIDs or prednisone was mentioned as the cause of the ulcer in 26 of 271 (9.6%) patients. Barrett’s esophagus was diagnosed in 29 of 342 (8.4%) patients in group I-GERD. In approximately 50% of the total number of patients, the investigation had been performed more than 5 years previously. Each patient had been treated accordingly during the subsequent years.
H pylori status was evaluated in 147 of the 692 patients (21%). In most of these cases the correspondence between the hospital staff and the GP did not mention current H pylori status. In addition, it remained unknown whether eradication therapy was administered with or without successful eradication of the microorganism (Table 3).
No investigations were performed in 230 of the 922 patients (25%). “Nonspecific stomach com-plaints” was the most common indication for ASDs in this group (Table 2).
TABLE 2
INDICATIONS FOR LONG-TERM (≥ 12 WEEKS) PRESCRIPTION OF LONG-TERM ACID SUPPRESSANT DRUGS
| No. (%) | |
|---|---|
| Final Diagnosis | 692 (75) |
| I-ULCER* | 271 (29) |
| Duodenal ulcer | 196 (21) |
| Duodenal and gastric ulcer | 17 (2) |
| Gastric ulcer | 43 (5) |
| Nonspecified ulcer | 15 (2) |
| I-GERD | 342 (37) |
| Esophagitis and ulcer* | 48 (5) |
| Esophagitis | 116 (13) |
| Esophagitis and hiatal hernia | 101 (11) |
| Symptomatic (hiatal hernia) | 77 (8) |
| I-FUNCTIONAL | 127 (14) |
| NI: Stomach Complaints | |
| Not Investigated | 230 (25) |
| Preventive | 45 (5) |
| Nonspecific stomach complaints | 146 (16) |
| Refluxlike complaints | 27 (3) |
| Ulcerlike complaints | 6 (1) |
| Motilitylike complaints | 6 (1) |
| Group I-ULCER includes all patients with a duodenal, gastric, or nonspecified ulcer; group I-GERD includes all patients with symptomatic or erosive gastroesophageal reflux disease; group I-FUNCTIONAL includes patients with only gastritis or with no imaging abnormalities. No investigations were performed on patients in group NI. | |
| *Total equals more than 100% because 48 patients with esophagitis and ulcer disease are included in both I-ULCER and I-GERD. | |
TABLE 3
H PYLORI DIAGNOSTICS AND ERADICATION THERAPY PRESCRIPTIONS IN 692 INVESTIGATED PATIENTS*
| Final Diagnoses After Investigation† | H pylori Diagnostics Ordered, No. (%) | H pylori Eradication Therapy Prescribed, No.(%) |
|---|---|---|
| I-ULCER (n = 271) | 78 (29) | 34 (13) |
| I-GERD (n = 342) | 34 (10) | 7 (2) |
| I-FUNCTIONAL (n = 127) | 35 (28) | 7 (6) |
| * The current H pylori status, prescription, and success of eradication therapy often remained unknown. Group I-ULCER includes all patients with a duodenal, gastric, or nonspecified ulcer; group I-GERD includes all patients with symptomatic or erosive gastroesophageal reflux disease; group I-FUNCTIONAL includes patients with only gastritis or with no imaging abnormalities. | ||
| † Forty-eight patients with gastroesophageal reflux disease and ulcer disease were included in both I-ULCER and I-GERD. | ||
Discussion
During our 1-year study, 2% of patients used an ASD for more than 3 months, and 0.8% for more than 6 months. Data from other studies, although not entirely comparable with ours, give an impression of the magnitude of long-term ASD prescription in other countries. In London, 0.8% of the general practice population used an ASD for more than 6 months continuously, a situation comparable with our results.5 One third of these patients had a history of ulcer disease. In Dundee, 4.4% of patients in 6 gen-eral practices were authorized to receive maintenance therapy.6 Many had a history of confirmed ulcer disease (27%), esophagitis (23%), or both (6%). Investigations in 23% of all patients revealed gastritis, duodenitis, hiatal hernia, or no pathology.
ASDs were used continuously for more than 1 year by almost one fourth of patients for whom they were prescribed; prolongation of the prescription was usually based on diagnostic tests performed years before. According to the guidelines that were in use during the course of this study, the indication for maintenance ASD was justified for most patients.2
Almost one third of all patients had a history of ulcer and continued to take an ASD (only 48 had concomitant GERD). For most of them, the ASD was probably prescribed as a preventive treatment. H pylori diagnostics were performed in a minority of patients. The major change in the most recent version of the guidelines of the Dutch College of General Practitioners (1996) is the role of H pylori infection. Patients with duodenal ulcer (active or inactive) not caused by NSAID use should be treated with H pylori eradication therapy.7 In principle, long-term ASD use is not necessary after successful eradication of H pylori, since the ulcer is not likely to relapse.8,9 However, a few patients with severe concomitant symptoms of functional dyspepsia or reflux disease may require therapy despite successful H pylori eradication.9,10 It is the GP’s task to identify patients with a history of ulcer disease and to eradicate H pylori. The clinician can easily identify patients with a history of ulcer disease with the help of computerized prescription data and the patient’s history file. However, implementation of these systems remains an important issue. Many such patients are invisible to the GP because they are treated with repeated prescriptions and without further consultation and therefore are not treated for H pylori.
The current Dutch guidelines do not advise testing for H pylori in patients with GERD or functional dyspepsia; this approach, therefore, is still not common in the Netherlands. Not advising to test is consistent with guidelines developed with a primary care perspective but differs in fundamental ways from guidelines formulated by specialists.11,12 The role of H pylori in esophagitis and reflux disease is not clear.13 Whether successful eradication of H pylori leads to exacerbation of esophagitis because of the absence of acid buffering by H pylori–derived urease production has been debated.14 In our study, one third of the patients suffered from GERD, which is easy to control, but not to cure; patients often experience a relapse after tapering of ASDs. Intermittent treatment with ASDs and the use of antacids as an escape medication may be an effective approach for managing patients with uncomplicated GERD and reducing the use of ASDs.15,16
There is little difference in the pattern of ASD prescribing for patients with ulcer, GERD, or functional dyspepsia. This similarity is particularly interesting because most studies of patients with functional dyspepsia have shown no benefit with the use of ASDs or with the eradication of H pylori.17-22 In these patients it may be sensible to taper the use of ASDs gradually, supported by antacid use; to explore the level of psychosocial distress; and to advise on lifestyle improvement.23 Long-term medication was prescribed as a preventive measure for the remaining 25% of all long-term users and to patients not given an endoscopy or barium study. The guidelines advise further investigation after several empirical treatments and again before a long-term ASD is prescribed.
One notable finding was that the patient’s sex appeared to influence whether investigations were ordered. The fact that ulcer disease is overall less often diagnosed in women might explain why the GPs did not perform further diagnostic investigations in women. Anxiety for endoscopy in men or women is another reason for not having a confirmed working diagnosis. A small number of anxious patients who have underlying ulcer disease might benefit from a test-and-treat approach to H pylori infection. However, serology cannot differentiate between either present or past H pylori infection and between ulcer or nonulcer disease.
Patients often experience a fast relapse of symptoms after discontinuation of therapy that may be related to rebound acid hypersecretion.24-26 It is possible that the prescription pattern of physicians in a subset of dyspeptic patients, especially in those with acid-related dyspepsia, leads to dependence on long-term therapy.
Conclusions
The use of ASDs, especially proton-pump inhibitors, is becoming increasingly common. In general practice in the Amsterdam region, 2% of patients used long-term ASDs. Patients with ulcer disease may stop taking ASDs after apparently successful H pylori eradication. Other patients require additional proof of underlying disease and H pylori status to determine the subsequent treatment approach. Tapering strategies in patients with mild reflux disease or functional dyspepsia need to be developed. Research is also needed in the general practice setting to develop strategies for tapering ASDs in chronic dyspeptic patients.
1. Lamberts H, Brouwer HJ, Mohrs J. Reason for encounter-, episode-and process-oriented standard output from Transition Project. Department of General Practice/Family Medicine. University of Amsterdam; 1991.
2. Numans ME, de Wit NJ, Geerdes RHM, et al. NHG-Standaard Maagklachten. Huisarts en Wetenschap 1993;36:375-9.
3. Omzet top 10 geneesmiddelen 1994. Data en Feiten Selectie, Stichting Farmaceutische Kengetallen, Den Haag; 1995.
4. Centrale Medische Pharmaceutische Commissie van de Ziekenfondsraad. Farmacotherapeutisch Kompas; 1995.
5. Ryder SD, O’Reilly S, Miller RJ, et al. Long-term acid suppressing treatment in general practice. BMJ 1994;308:827-30.
6. Goudie BM, McKenzie PE, Cipriano J, et al. Repeat prescribing of ulcer healing drugs in general practice—prevalence and underlying diagnosis. Aliment Pharmacol Ther 1996;10:147-50.
7. Numans ME, de Wit NJ, Geerdes RHM, et al. NHG-Standaard Maagklachten. Huisarts en Wetenschap 1996;39:565-77.
8. Van der Hulst RWM, Rauws EAJ, Köycu B, et al. Prevention of ulcer recurrence after eradication of H pylori infection: a prospective long-term follow-up study. Gastroenterology 1997;113:1082-6.
9. Hurenkamp GJB, Grundmeijer HGLM, van der Ende A, Tytgat GNJ, Assendelft WJJ, van der Hulst RWM. Arrest of chronic acid suppressant drug use after successful Helicobacter pylori eradication in patients with peptic ulcer disease: a six-month follow-up study. Aliment Pharmacol Ther 2001;15:1047-54.
10. Boyd EJ. The prevalence of esophagitis in patients with duodenal ulcer or ulcer-like dyspepsia. Am J Gastroenterol 1996;91:1539-43.
11. Meineche-Schmidt V, Rubin G, de Wit NJ. Helicobacter pylori infection: a comparative review of existing managment guidelines. Fam Pract 2000;17(suppl 2):S2-S5.
12. American Gastroenterological Association. Medical Position Statement: Evaluation of dyspepsia. Gastroenterology 1998;114:579-81.
13. Labenz J, Malfertheiner P. Helicobacter pylori in gastroesophageal reflux disease: causal agent, independent or protective factor? Gut 1997;41:277-80.
14. Labenz J, Tillenburg B, Peitz U, et al. Helicobacter pylori augments the pH-increasing effect of omeprazole in patients with duodenal ulcer. Gastroenterology 1996;110:725-32.
15. Bardhan KD, Müller-Lissner S, Bigard MA, et al. Symptomatic gastroesophageal reflux disease: double-blind controlled study of intermittent treatment with omeprazole or ranitidine. BMJ 1999;318:502-7.
16. Talley NJ, Lauritsen K, Tunturi-hihnala H, et al. Esomeprazole 20 mg maintains symptom control in endoscopy-negative gastroesophageal reflux disease: a controlled trial of “on-demand” therapy for 6 months. Aliment Pharmacol Ther 2001;15:347-54.
17. Talley NJ. A critique of therapeutic trials in Helicobacter pylori–postive functional dyspepsia. Gastroenterology 1994;106:1174-83.
18. Veldhuizen SJO, Cleary C, Talley NJ, et al. Drug treatment of functional dyspepsia: a systematic analysis of trial methodology with recommendations for design of future trials. Am J Gastroenterol 1996;4:660-73.
19. Laheij RJF, Jansen JBMJ, van de Lisdonk EH, et al. Review article: symptom improvement through eradication of H pylori in patients with non-ulcer dyspepsia. Aliment Pharmacol Ther 1996;10:843-50.
20. Blum AL, Talley NJ, O’Morain C, et al. Lack of effect of treating Helicobacter pylori infection in patients with nonulcer dyspepsia. N Engl J Med 1998;339:1875-81.
21. McColl K, Murray L, El-Omar E, et al. Symptomatic benefit from eradicating Helicobacter pylori infection in patients with nonulcer dyspepsia. N Engl J Med 1998;339:1869-74.
22. Talley NJ, Jansssens J, Lauritsen K, et al. Eradication of H pylori in functional dyspepsia: randomised double blind placebo controlled trial with 12 months’ follow up. BMJ 1999;318:833-7.
23. Quartero AO, Post MWM, Numans ME, et al. What makes the dyspeptic patient feel ill? A cross-sectional survey of functional health status, H pylori infection, and psychological distress in dyspeptic patients in general practice. Gut 1999;45:15-9.
24. El-Omar E, Banerjee S, Wirz BN, Penman I, Ardill JES, McColl KEL. Marked rebound acid hypersecretion after treatment with ranitidine. Am J Gastroenterology 1996;91:355-9.
25. Fullarton GM, McLauchlan G, McDonald A, Crean GP, McColl KEL. Rebound nocturnal hypersecretion after four weeks of treatment with an H2-receptor antagonist. Gut 1998;42:159-65.
26. Gillen D, Wirz AA, Ardill JE, McColl KE. Rebound acid hypersecretion after omeprazole and its relation to on-treatment acid suppression and Helicobacter pylori status. Gastroenterology 1999;116:239-47.
OBJECTIVES: A considerable proportion of the medication budget of Dutch general practitioners is spent on prescribed long-term acid suppressant drugs. We investigated the magnitude of long-term prescription of acid suppressant drugs in general practice and the frequency and means of confirming the primary working diagnosis.
STUDY DESIGN: We used a retrospective descriptive study of 24 general practices in the Amsterdam region.
POPULATION: We identified those receiving long-term acid suppressant therapy (12 or more weeks/year) from a total of 46,813 patients by extracting data from pharmacy databases.
OUTCOMES MEASURED: We measured the amount and duration of prescriptions for each medication, indications for prescription, and investigations performed by general practitioners.
RESULTS: Of the 46,813 patients, 922 (2%) received long-term acid suppressant therapy. The duration of prescription varied from 12 weeks in 8% of patients to > 52 weeks in 23% of patients (mean = 33 weeks). In 25% of patients, no investigations were performed; 75% of patients underwent endoscopy or ingested a barium meal. The predominant diagnoses in investigated patients were ulcer disease (39%), gastroesophageal reflux disease (49%), and functional dyspepsia (gastritis, normal aspect; 18%). Helicobacter pylori status was available in 29% of patients with ulcer disease. Eradication therapy was reported in 44% of these patients.
CONCLUSIONS: Among patients of physicians in general practice in the Amsterdam region, 2% used long-term acid suppressants. Patients with ulcer disease may stop taking acid suppressants after apparent successful H pylori eradication. Tapering strategies must be developed for patients with mild reflux disease or functional dyspepsia.
- In Dutch general practice, 2% of patients take long-term acid suppressant drugs.
- One third of patients taking long-term acid suppressant drugs have peptic ulcer disease and may not need medication as soon as Helicobacter pylori has been eradicated.
- One fourth of patients taking long-term acid suppressant drugs have never undergone endoscopy or barium study.
- Because patients often do not tolerate sudden cessation of chronic acid suppressant drug use, tapering strategies must be developed.
The average Dutch general practice includes approximately 2350 patients. Of these, 2 to 3 per week, on average, visit their general practitioner (GP) with a complaint of dyspepsia.1 According to the guidelines of the Dutch College of General Practitioners, the treatment of dyspepsia is directed toward symptom relief, usually on an empirical basis, except for patients with symptoms such as sudden weight loss or hematemesis that suggest cancer; these are referred for endoscopy.2 Medication is prescribed in a stepwise fashion from less potent antacids and prokinetics to the more potent H2-blockers and proton pump inhibitors. During our study, long-term treatment with acid suppressant drugs (ASDs) was indicated only for relapsing ulcers or ulcerlike complaints, relapsing esophagitis, and relapsing gastroesophageal refluxlike symptoms.2
ASDs are responsible for a disproportionate share of the medication budget of Dutch GPs because of their high cost, their high frequency of prescription, and their use on a long-term basis.3 We therefore wondered whether the indication for prescribing an ASD was always appropriate. The aim of our study was to describe how commonly ASDs are prescribed and to describe the initial working diagnosis, the diagnostic tests performed to confirm the working hypothesis, and the final diagnosis for each patient.
Methods
Patients
We retrospectively collected data from 24 general practices in Amsterdam from September 1994 to August 1995 on patients taking long-term ASDs (12 or more weeks during the previous year). ASDs included antacids, mucosa-protective agents, prokinetics, H2-blockers, and proton pump inhibitors.4
Patients were identified from a medication database obtained from all cooperating pharmacists that included patient demographics; type, dose, and duration of medications; and use of possible risk-bearing comedications (aspirin, nonsteroidal anti-inflammatory drugs, or prednisone for more than 6 weeks during the study year). In this way we were able to identify almost all patients from the participating general practices who received long-term treatment with ASDs.
Confirmation of gastrointestinal diagnosis
In the Netherlands, a GP receives all available medical information on his patients (ie, letters from specialists, results from any examinations performed) and stores this information in the patient’s medical history file. When a patient switches to another GP, the entire medical history is sent to this new physician. Our principal investigator used these medical history files to determine the diagnosis and reason for the ASD prescription and the diagnostic tests (including Helicobacter pylori investigations) that were ordered to confirm the working diagnosis. Gastroscopy or barium meal radiography at any time during a patient’s life was considered the investigation for confirmation of the diagnosis. If the prescription started after this investigation or as a consequence of it, the investigation was considered the reason for initiating the current long-term treatment. Verification and completion of the obtained data took place in a face-to-face evaluation between the principal investigator and the GP, ensuring the completeness and reliability of the data.
Analysis and statistics
Patients were categorized into group I (investigations to confirm a working diagnosis were performed) and group NI (no investigations were performed). Three subgroups were identified within group I. We included all patients with a duodenal, gastric, or unspecified ulcer in group I-ULCER; group I-GERD included all patients with symptomatic or erosive gastroesophageal reflux disease (GERD); and group I-FUNCTIONAL included patients with only gastritis or with no imaging abnormalities. Patients with an ulcer and esophagitis were placed in group I-ULCER for their patient characteristics and medication prescription and in both groups I-ULCER and I-GERD for their medication indication, diagnostic tests, and eradication of H pylori.
Data were analyzed with the use of Statistical Package for the Social Sciences software (version 7.5.3). The chi-square test was used for comparison of proportions. Significance was set at = .05 (two sided).
Results
General characteristics and medication prescription
Of 46,813 patients listed with the 24 general practices, 988 (2.1%) were identified as long-term users of ASDs. Of these 988 patients, 66 were excluded because of ASD use for gastric or esophageal cancer, nongastric-related indications such as renal failure, or discontinuation of visits to the GP (patient moved or was a temporary visitor). The demographic and prescription characteristics of the remaining 922 patients are presented in Table 1. All patients had used H2-blockers and proton pump inhibitors for 12 weeks or more during the previous year.
Group I-ULCER consisted of 271 ulcer patients; group I-GERD, of 294 patients with reflux disease; and group I-FUNCTIONAL, of 127 patients with functional dyspepsia. Group NI consisted of 230 patients who did not undergo any confirmatory diagnostic testing (no endoscopy or barium study). Among the long-term users, treatment was more frequently prescribed for women than men (55% vs 45%, respectively; P < .05). Women were more likely not to undergo any diagnostic investigation (28% vs 21%, P < .05). If investigated, however, women were less likely than men have an ulcer (30% vs 50%, P < .05) and more likely to have functional dyspepsia (25% vs 11%, P < .05).
Overall, ranitidine was the drug most commonly prescribed. The mean duration of prescription was 33 weeks in the year of study, with a high of 38 weeks in group I-GERD. Almost one fourth of all patients (23%) had been using these drugs for more than 1 year. In more than half of all patients (53%), the medication was prescribed for 1 episode; in the other 47%, medication was prescribed for 2 or more episodes (ie, intermittent prescription). During the study period, 154 patients (17%) had used potential risk-bearing comedication for more than 6 weeks, including 48 with ulcer.
TABLE 1
CHARACTERISTICS AND PRESCRIPTIONS IN 922 PATIENTS (%) WITH LONG-TERM ACID SUPPRESSANT DRUG PRESCRIPTION IN 24 GENERAL PRACTICES IN THE REGION OF AMSTERDAM, THE NETHERLANDS
| DIAGNOSIS AFTER INVESTIGATION | |||||
|---|---|---|---|---|---|
| Characteristics | Total (N=922) | I-ULCER (n = 271) | I-GERD (n = 294) | I-FUNCTIONAL (n = 127) | NI: Stomach Complaints Without Investigation (n = 230) |
| Patients | |||||
| Female | 511 (55) | 41% | 57% | 72% | 62% |
| 15–44 years | 169 (18) | 11% | 17% | 25% | 25% |
| Mean age, years | 61 | 63 | 63 | 57 | 59 |
| Medication, No. | |||||
| Ranitidine | 442 (48) | 141 (52) | 115 (39) | 70 (55) | 116 (50) |
| Cimetidine | 236 (26) | 82 (30) | 48 (16) | 39 (31) | 67 (29) |
| Omeprazole | 241 (26) | 63 (23) | 130 (44) | 22 (17) | 26 (11) |
| Famotidine | 43 (5) | 16 (6) | 15 (5) | 4 (3) | 8 (3) |
| Lansoprazole | 13 (1) | 3 (1) | 5 (2) | 5 (4) | 0 (0) |
| Prescription Time | |||||
| 12–19 weeks | 231 (25) | 67 (25) | 44 (15) | 44 (35) | 76 (33) |
| 20–29 weeks | 184 (20) | 56 (21) | 46 (16) | 27 (21) | 55 (24) |
| 30–39 weeks | 148 (16) | 40 (15) | 50 (17) | 22 (17) | 36 (16) |
| 40–51 weeks | 143 (16) | 44 (16) | 60 (20) | 15 (12) | 24 (10) |
| >52 weeks | 216 (23) | 64 (24) | 94 (32) | 19 (15) | 39 (17) |
| Mean, weeks | 33 | 34 | 38 | 29 | 29 |
| No. of Episodes of Prescription | |||||
| 1 | 485 (53) | 144 (53) | 179 (61) | 51 (40) | 111 (48) |
| 2 | 271 (29) | 78 (29) | 81 (28) | 48 (38) | 64 (28) |
| > 2 | 166 (18) | 49 (18) | 34 (12) | 28 (22) | 55 (24) |
| Group I-ULCER includes all patients with a duodenal, -gastric, or nonspecified ulcer; group I-GERD includes all patients with symptomatic or erosive gastroesophageal reflux disease; group I-FUNCTIONAL includes patients with gastritis or with normal aspect on endoscopy or barium meal. | |||||
| *Total equals more than 100% because of different types of medication per patient; rarely prescribed medications are not mentioned. | |||||
Confirmation of working diagnosis
In 692 of the 922 (75%) patients a diagnostic test was performed to confirm the primary working diagnosis. In 519 (75%), a gastroscopy was performed and in 138 (20%) a barium meal radiograph was taken. In 35 patients, the specific form of investigation was unclear.
The specific diagnoses of the subgroups are shown in Table 2. In patients with ulcer, use of NSAIDs or prednisone was mentioned as the cause of the ulcer in 26 of 271 (9.6%) patients. Barrett’s esophagus was diagnosed in 29 of 342 (8.4%) patients in group I-GERD. In approximately 50% of the total number of patients, the investigation had been performed more than 5 years previously. Each patient had been treated accordingly during the subsequent years.
H pylori status was evaluated in 147 of the 692 patients (21%). In most of these cases the correspondence between the hospital staff and the GP did not mention current H pylori status. In addition, it remained unknown whether eradication therapy was administered with or without successful eradication of the microorganism (Table 3).
No investigations were performed in 230 of the 922 patients (25%). “Nonspecific stomach com-plaints” was the most common indication for ASDs in this group (Table 2).
TABLE 2
INDICATIONS FOR LONG-TERM (≥ 12 WEEKS) PRESCRIPTION OF LONG-TERM ACID SUPPRESSANT DRUGS
| No. (%) | |
|---|---|
| Final Diagnosis | 692 (75) |
| I-ULCER* | 271 (29) |
| Duodenal ulcer | 196 (21) |
| Duodenal and gastric ulcer | 17 (2) |
| Gastric ulcer | 43 (5) |
| Nonspecified ulcer | 15 (2) |
| I-GERD | 342 (37) |
| Esophagitis and ulcer* | 48 (5) |
| Esophagitis | 116 (13) |
| Esophagitis and hiatal hernia | 101 (11) |
| Symptomatic (hiatal hernia) | 77 (8) |
| I-FUNCTIONAL | 127 (14) |
| NI: Stomach Complaints | |
| Not Investigated | 230 (25) |
| Preventive | 45 (5) |
| Nonspecific stomach complaints | 146 (16) |
| Refluxlike complaints | 27 (3) |
| Ulcerlike complaints | 6 (1) |
| Motilitylike complaints | 6 (1) |
| Group I-ULCER includes all patients with a duodenal, gastric, or nonspecified ulcer; group I-GERD includes all patients with symptomatic or erosive gastroesophageal reflux disease; group I-FUNCTIONAL includes patients with only gastritis or with no imaging abnormalities. No investigations were performed on patients in group NI. | |
| *Total equals more than 100% because 48 patients with esophagitis and ulcer disease are included in both I-ULCER and I-GERD. | |
TABLE 3
H PYLORI DIAGNOSTICS AND ERADICATION THERAPY PRESCRIPTIONS IN 692 INVESTIGATED PATIENTS*
| Final Diagnoses After Investigation† | H pylori Diagnostics Ordered, No. (%) | H pylori Eradication Therapy Prescribed, No.(%) |
|---|---|---|
| I-ULCER (n = 271) | 78 (29) | 34 (13) |
| I-GERD (n = 342) | 34 (10) | 7 (2) |
| I-FUNCTIONAL (n = 127) | 35 (28) | 7 (6) |
| * The current H pylori status, prescription, and success of eradication therapy often remained unknown. Group I-ULCER includes all patients with a duodenal, gastric, or nonspecified ulcer; group I-GERD includes all patients with symptomatic or erosive gastroesophageal reflux disease; group I-FUNCTIONAL includes patients with only gastritis or with no imaging abnormalities. | ||
| † Forty-eight patients with gastroesophageal reflux disease and ulcer disease were included in both I-ULCER and I-GERD. | ||
Discussion
During our 1-year study, 2% of patients used an ASD for more than 3 months, and 0.8% for more than 6 months. Data from other studies, although not entirely comparable with ours, give an impression of the magnitude of long-term ASD prescription in other countries. In London, 0.8% of the general practice population used an ASD for more than 6 months continuously, a situation comparable with our results.5 One third of these patients had a history of ulcer disease. In Dundee, 4.4% of patients in 6 gen-eral practices were authorized to receive maintenance therapy.6 Many had a history of confirmed ulcer disease (27%), esophagitis (23%), or both (6%). Investigations in 23% of all patients revealed gastritis, duodenitis, hiatal hernia, or no pathology.
ASDs were used continuously for more than 1 year by almost one fourth of patients for whom they were prescribed; prolongation of the prescription was usually based on diagnostic tests performed years before. According to the guidelines that were in use during the course of this study, the indication for maintenance ASD was justified for most patients.2
Almost one third of all patients had a history of ulcer and continued to take an ASD (only 48 had concomitant GERD). For most of them, the ASD was probably prescribed as a preventive treatment. H pylori diagnostics were performed in a minority of patients. The major change in the most recent version of the guidelines of the Dutch College of General Practitioners (1996) is the role of H pylori infection. Patients with duodenal ulcer (active or inactive) not caused by NSAID use should be treated with H pylori eradication therapy.7 In principle, long-term ASD use is not necessary after successful eradication of H pylori, since the ulcer is not likely to relapse.8,9 However, a few patients with severe concomitant symptoms of functional dyspepsia or reflux disease may require therapy despite successful H pylori eradication.9,10 It is the GP’s task to identify patients with a history of ulcer disease and to eradicate H pylori. The clinician can easily identify patients with a history of ulcer disease with the help of computerized prescription data and the patient’s history file. However, implementation of these systems remains an important issue. Many such patients are invisible to the GP because they are treated with repeated prescriptions and without further consultation and therefore are not treated for H pylori.
The current Dutch guidelines do not advise testing for H pylori in patients with GERD or functional dyspepsia; this approach, therefore, is still not common in the Netherlands. Not advising to test is consistent with guidelines developed with a primary care perspective but differs in fundamental ways from guidelines formulated by specialists.11,12 The role of H pylori in esophagitis and reflux disease is not clear.13 Whether successful eradication of H pylori leads to exacerbation of esophagitis because of the absence of acid buffering by H pylori–derived urease production has been debated.14 In our study, one third of the patients suffered from GERD, which is easy to control, but not to cure; patients often experience a relapse after tapering of ASDs. Intermittent treatment with ASDs and the use of antacids as an escape medication may be an effective approach for managing patients with uncomplicated GERD and reducing the use of ASDs.15,16
There is little difference in the pattern of ASD prescribing for patients with ulcer, GERD, or functional dyspepsia. This similarity is particularly interesting because most studies of patients with functional dyspepsia have shown no benefit with the use of ASDs or with the eradication of H pylori.17-22 In these patients it may be sensible to taper the use of ASDs gradually, supported by antacid use; to explore the level of psychosocial distress; and to advise on lifestyle improvement.23 Long-term medication was prescribed as a preventive measure for the remaining 25% of all long-term users and to patients not given an endoscopy or barium study. The guidelines advise further investigation after several empirical treatments and again before a long-term ASD is prescribed.
One notable finding was that the patient’s sex appeared to influence whether investigations were ordered. The fact that ulcer disease is overall less often diagnosed in women might explain why the GPs did not perform further diagnostic investigations in women. Anxiety for endoscopy in men or women is another reason for not having a confirmed working diagnosis. A small number of anxious patients who have underlying ulcer disease might benefit from a test-and-treat approach to H pylori infection. However, serology cannot differentiate between either present or past H pylori infection and between ulcer or nonulcer disease.
Patients often experience a fast relapse of symptoms after discontinuation of therapy that may be related to rebound acid hypersecretion.24-26 It is possible that the prescription pattern of physicians in a subset of dyspeptic patients, especially in those with acid-related dyspepsia, leads to dependence on long-term therapy.
Conclusions
The use of ASDs, especially proton-pump inhibitors, is becoming increasingly common. In general practice in the Amsterdam region, 2% of patients used long-term ASDs. Patients with ulcer disease may stop taking ASDs after apparently successful H pylori eradication. Other patients require additional proof of underlying disease and H pylori status to determine the subsequent treatment approach. Tapering strategies in patients with mild reflux disease or functional dyspepsia need to be developed. Research is also needed in the general practice setting to develop strategies for tapering ASDs in chronic dyspeptic patients.
OBJECTIVES: A considerable proportion of the medication budget of Dutch general practitioners is spent on prescribed long-term acid suppressant drugs. We investigated the magnitude of long-term prescription of acid suppressant drugs in general practice and the frequency and means of confirming the primary working diagnosis.
STUDY DESIGN: We used a retrospective descriptive study of 24 general practices in the Amsterdam region.
POPULATION: We identified those receiving long-term acid suppressant therapy (12 or more weeks/year) from a total of 46,813 patients by extracting data from pharmacy databases.
OUTCOMES MEASURED: We measured the amount and duration of prescriptions for each medication, indications for prescription, and investigations performed by general practitioners.
RESULTS: Of the 46,813 patients, 922 (2%) received long-term acid suppressant therapy. The duration of prescription varied from 12 weeks in 8% of patients to > 52 weeks in 23% of patients (mean = 33 weeks). In 25% of patients, no investigations were performed; 75% of patients underwent endoscopy or ingested a barium meal. The predominant diagnoses in investigated patients were ulcer disease (39%), gastroesophageal reflux disease (49%), and functional dyspepsia (gastritis, normal aspect; 18%). Helicobacter pylori status was available in 29% of patients with ulcer disease. Eradication therapy was reported in 44% of these patients.
CONCLUSIONS: Among patients of physicians in general practice in the Amsterdam region, 2% used long-term acid suppressants. Patients with ulcer disease may stop taking acid suppressants after apparent successful H pylori eradication. Tapering strategies must be developed for patients with mild reflux disease or functional dyspepsia.
- In Dutch general practice, 2% of patients take long-term acid suppressant drugs.
- One third of patients taking long-term acid suppressant drugs have peptic ulcer disease and may not need medication as soon as Helicobacter pylori has been eradicated.
- One fourth of patients taking long-term acid suppressant drugs have never undergone endoscopy or barium study.
- Because patients often do not tolerate sudden cessation of chronic acid suppressant drug use, tapering strategies must be developed.
The average Dutch general practice includes approximately 2350 patients. Of these, 2 to 3 per week, on average, visit their general practitioner (GP) with a complaint of dyspepsia.1 According to the guidelines of the Dutch College of General Practitioners, the treatment of dyspepsia is directed toward symptom relief, usually on an empirical basis, except for patients with symptoms such as sudden weight loss or hematemesis that suggest cancer; these are referred for endoscopy.2 Medication is prescribed in a stepwise fashion from less potent antacids and prokinetics to the more potent H2-blockers and proton pump inhibitors. During our study, long-term treatment with acid suppressant drugs (ASDs) was indicated only for relapsing ulcers or ulcerlike complaints, relapsing esophagitis, and relapsing gastroesophageal refluxlike symptoms.2
ASDs are responsible for a disproportionate share of the medication budget of Dutch GPs because of their high cost, their high frequency of prescription, and their use on a long-term basis.3 We therefore wondered whether the indication for prescribing an ASD was always appropriate. The aim of our study was to describe how commonly ASDs are prescribed and to describe the initial working diagnosis, the diagnostic tests performed to confirm the working hypothesis, and the final diagnosis for each patient.
Methods
Patients
We retrospectively collected data from 24 general practices in Amsterdam from September 1994 to August 1995 on patients taking long-term ASDs (12 or more weeks during the previous year). ASDs included antacids, mucosa-protective agents, prokinetics, H2-blockers, and proton pump inhibitors.4
Patients were identified from a medication database obtained from all cooperating pharmacists that included patient demographics; type, dose, and duration of medications; and use of possible risk-bearing comedications (aspirin, nonsteroidal anti-inflammatory drugs, or prednisone for more than 6 weeks during the study year). In this way we were able to identify almost all patients from the participating general practices who received long-term treatment with ASDs.
Confirmation of gastrointestinal diagnosis
In the Netherlands, a GP receives all available medical information on his patients (ie, letters from specialists, results from any examinations performed) and stores this information in the patient’s medical history file. When a patient switches to another GP, the entire medical history is sent to this new physician. Our principal investigator used these medical history files to determine the diagnosis and reason for the ASD prescription and the diagnostic tests (including Helicobacter pylori investigations) that were ordered to confirm the working diagnosis. Gastroscopy or barium meal radiography at any time during a patient’s life was considered the investigation for confirmation of the diagnosis. If the prescription started after this investigation or as a consequence of it, the investigation was considered the reason for initiating the current long-term treatment. Verification and completion of the obtained data took place in a face-to-face evaluation between the principal investigator and the GP, ensuring the completeness and reliability of the data.
Analysis and statistics
Patients were categorized into group I (investigations to confirm a working diagnosis were performed) and group NI (no investigations were performed). Three subgroups were identified within group I. We included all patients with a duodenal, gastric, or unspecified ulcer in group I-ULCER; group I-GERD included all patients with symptomatic or erosive gastroesophageal reflux disease (GERD); and group I-FUNCTIONAL included patients with only gastritis or with no imaging abnormalities. Patients with an ulcer and esophagitis were placed in group I-ULCER for their patient characteristics and medication prescription and in both groups I-ULCER and I-GERD for their medication indication, diagnostic tests, and eradication of H pylori.
Data were analyzed with the use of Statistical Package for the Social Sciences software (version 7.5.3). The chi-square test was used for comparison of proportions. Significance was set at = .05 (two sided).
Results
General characteristics and medication prescription
Of 46,813 patients listed with the 24 general practices, 988 (2.1%) were identified as long-term users of ASDs. Of these 988 patients, 66 were excluded because of ASD use for gastric or esophageal cancer, nongastric-related indications such as renal failure, or discontinuation of visits to the GP (patient moved or was a temporary visitor). The demographic and prescription characteristics of the remaining 922 patients are presented in Table 1. All patients had used H2-blockers and proton pump inhibitors for 12 weeks or more during the previous year.
Group I-ULCER consisted of 271 ulcer patients; group I-GERD, of 294 patients with reflux disease; and group I-FUNCTIONAL, of 127 patients with functional dyspepsia. Group NI consisted of 230 patients who did not undergo any confirmatory diagnostic testing (no endoscopy or barium study). Among the long-term users, treatment was more frequently prescribed for women than men (55% vs 45%, respectively; P < .05). Women were more likely not to undergo any diagnostic investigation (28% vs 21%, P < .05). If investigated, however, women were less likely than men have an ulcer (30% vs 50%, P < .05) and more likely to have functional dyspepsia (25% vs 11%, P < .05).
Overall, ranitidine was the drug most commonly prescribed. The mean duration of prescription was 33 weeks in the year of study, with a high of 38 weeks in group I-GERD. Almost one fourth of all patients (23%) had been using these drugs for more than 1 year. In more than half of all patients (53%), the medication was prescribed for 1 episode; in the other 47%, medication was prescribed for 2 or more episodes (ie, intermittent prescription). During the study period, 154 patients (17%) had used potential risk-bearing comedication for more than 6 weeks, including 48 with ulcer.
TABLE 1
CHARACTERISTICS AND PRESCRIPTIONS IN 922 PATIENTS (%) WITH LONG-TERM ACID SUPPRESSANT DRUG PRESCRIPTION IN 24 GENERAL PRACTICES IN THE REGION OF AMSTERDAM, THE NETHERLANDS
| DIAGNOSIS AFTER INVESTIGATION | |||||
|---|---|---|---|---|---|
| Characteristics | Total (N=922) | I-ULCER (n = 271) | I-GERD (n = 294) | I-FUNCTIONAL (n = 127) | NI: Stomach Complaints Without Investigation (n = 230) |
| Patients | |||||
| Female | 511 (55) | 41% | 57% | 72% | 62% |
| 15–44 years | 169 (18) | 11% | 17% | 25% | 25% |
| Mean age, years | 61 | 63 | 63 | 57 | 59 |
| Medication, No. | |||||
| Ranitidine | 442 (48) | 141 (52) | 115 (39) | 70 (55) | 116 (50) |
| Cimetidine | 236 (26) | 82 (30) | 48 (16) | 39 (31) | 67 (29) |
| Omeprazole | 241 (26) | 63 (23) | 130 (44) | 22 (17) | 26 (11) |
| Famotidine | 43 (5) | 16 (6) | 15 (5) | 4 (3) | 8 (3) |
| Lansoprazole | 13 (1) | 3 (1) | 5 (2) | 5 (4) | 0 (0) |
| Prescription Time | |||||
| 12–19 weeks | 231 (25) | 67 (25) | 44 (15) | 44 (35) | 76 (33) |
| 20–29 weeks | 184 (20) | 56 (21) | 46 (16) | 27 (21) | 55 (24) |
| 30–39 weeks | 148 (16) | 40 (15) | 50 (17) | 22 (17) | 36 (16) |
| 40–51 weeks | 143 (16) | 44 (16) | 60 (20) | 15 (12) | 24 (10) |
| >52 weeks | 216 (23) | 64 (24) | 94 (32) | 19 (15) | 39 (17) |
| Mean, weeks | 33 | 34 | 38 | 29 | 29 |
| No. of Episodes of Prescription | |||||
| 1 | 485 (53) | 144 (53) | 179 (61) | 51 (40) | 111 (48) |
| 2 | 271 (29) | 78 (29) | 81 (28) | 48 (38) | 64 (28) |
| > 2 | 166 (18) | 49 (18) | 34 (12) | 28 (22) | 55 (24) |
| Group I-ULCER includes all patients with a duodenal, -gastric, or nonspecified ulcer; group I-GERD includes all patients with symptomatic or erosive gastroesophageal reflux disease; group I-FUNCTIONAL includes patients with gastritis or with normal aspect on endoscopy or barium meal. | |||||
| *Total equals more than 100% because of different types of medication per patient; rarely prescribed medications are not mentioned. | |||||
Confirmation of working diagnosis
In 692 of the 922 (75%) patients a diagnostic test was performed to confirm the primary working diagnosis. In 519 (75%), a gastroscopy was performed and in 138 (20%) a barium meal radiograph was taken. In 35 patients, the specific form of investigation was unclear.
The specific diagnoses of the subgroups are shown in Table 2. In patients with ulcer, use of NSAIDs or prednisone was mentioned as the cause of the ulcer in 26 of 271 (9.6%) patients. Barrett’s esophagus was diagnosed in 29 of 342 (8.4%) patients in group I-GERD. In approximately 50% of the total number of patients, the investigation had been performed more than 5 years previously. Each patient had been treated accordingly during the subsequent years.
H pylori status was evaluated in 147 of the 692 patients (21%). In most of these cases the correspondence between the hospital staff and the GP did not mention current H pylori status. In addition, it remained unknown whether eradication therapy was administered with or without successful eradication of the microorganism (Table 3).
No investigations were performed in 230 of the 922 patients (25%). “Nonspecific stomach com-plaints” was the most common indication for ASDs in this group (Table 2).
TABLE 2
INDICATIONS FOR LONG-TERM (≥ 12 WEEKS) PRESCRIPTION OF LONG-TERM ACID SUPPRESSANT DRUGS
| No. (%) | |
|---|---|
| Final Diagnosis | 692 (75) |
| I-ULCER* | 271 (29) |
| Duodenal ulcer | 196 (21) |
| Duodenal and gastric ulcer | 17 (2) |
| Gastric ulcer | 43 (5) |
| Nonspecified ulcer | 15 (2) |
| I-GERD | 342 (37) |
| Esophagitis and ulcer* | 48 (5) |
| Esophagitis | 116 (13) |
| Esophagitis and hiatal hernia | 101 (11) |
| Symptomatic (hiatal hernia) | 77 (8) |
| I-FUNCTIONAL | 127 (14) |
| NI: Stomach Complaints | |
| Not Investigated | 230 (25) |
| Preventive | 45 (5) |
| Nonspecific stomach complaints | 146 (16) |
| Refluxlike complaints | 27 (3) |
| Ulcerlike complaints | 6 (1) |
| Motilitylike complaints | 6 (1) |
| Group I-ULCER includes all patients with a duodenal, gastric, or nonspecified ulcer; group I-GERD includes all patients with symptomatic or erosive gastroesophageal reflux disease; group I-FUNCTIONAL includes patients with only gastritis or with no imaging abnormalities. No investigations were performed on patients in group NI. | |
| *Total equals more than 100% because 48 patients with esophagitis and ulcer disease are included in both I-ULCER and I-GERD. | |
TABLE 3
H PYLORI DIAGNOSTICS AND ERADICATION THERAPY PRESCRIPTIONS IN 692 INVESTIGATED PATIENTS*
| Final Diagnoses After Investigation† | H pylori Diagnostics Ordered, No. (%) | H pylori Eradication Therapy Prescribed, No.(%) |
|---|---|---|
| I-ULCER (n = 271) | 78 (29) | 34 (13) |
| I-GERD (n = 342) | 34 (10) | 7 (2) |
| I-FUNCTIONAL (n = 127) | 35 (28) | 7 (6) |
| * The current H pylori status, prescription, and success of eradication therapy often remained unknown. Group I-ULCER includes all patients with a duodenal, gastric, or nonspecified ulcer; group I-GERD includes all patients with symptomatic or erosive gastroesophageal reflux disease; group I-FUNCTIONAL includes patients with only gastritis or with no imaging abnormalities. | ||
| † Forty-eight patients with gastroesophageal reflux disease and ulcer disease were included in both I-ULCER and I-GERD. | ||
Discussion
During our 1-year study, 2% of patients used an ASD for more than 3 months, and 0.8% for more than 6 months. Data from other studies, although not entirely comparable with ours, give an impression of the magnitude of long-term ASD prescription in other countries. In London, 0.8% of the general practice population used an ASD for more than 6 months continuously, a situation comparable with our results.5 One third of these patients had a history of ulcer disease. In Dundee, 4.4% of patients in 6 gen-eral practices were authorized to receive maintenance therapy.6 Many had a history of confirmed ulcer disease (27%), esophagitis (23%), or both (6%). Investigations in 23% of all patients revealed gastritis, duodenitis, hiatal hernia, or no pathology.
ASDs were used continuously for more than 1 year by almost one fourth of patients for whom they were prescribed; prolongation of the prescription was usually based on diagnostic tests performed years before. According to the guidelines that were in use during the course of this study, the indication for maintenance ASD was justified for most patients.2
Almost one third of all patients had a history of ulcer and continued to take an ASD (only 48 had concomitant GERD). For most of them, the ASD was probably prescribed as a preventive treatment. H pylori diagnostics were performed in a minority of patients. The major change in the most recent version of the guidelines of the Dutch College of General Practitioners (1996) is the role of H pylori infection. Patients with duodenal ulcer (active or inactive) not caused by NSAID use should be treated with H pylori eradication therapy.7 In principle, long-term ASD use is not necessary after successful eradication of H pylori, since the ulcer is not likely to relapse.8,9 However, a few patients with severe concomitant symptoms of functional dyspepsia or reflux disease may require therapy despite successful H pylori eradication.9,10 It is the GP’s task to identify patients with a history of ulcer disease and to eradicate H pylori. The clinician can easily identify patients with a history of ulcer disease with the help of computerized prescription data and the patient’s history file. However, implementation of these systems remains an important issue. Many such patients are invisible to the GP because they are treated with repeated prescriptions and without further consultation and therefore are not treated for H pylori.
The current Dutch guidelines do not advise testing for H pylori in patients with GERD or functional dyspepsia; this approach, therefore, is still not common in the Netherlands. Not advising to test is consistent with guidelines developed with a primary care perspective but differs in fundamental ways from guidelines formulated by specialists.11,12 The role of H pylori in esophagitis and reflux disease is not clear.13 Whether successful eradication of H pylori leads to exacerbation of esophagitis because of the absence of acid buffering by H pylori–derived urease production has been debated.14 In our study, one third of the patients suffered from GERD, which is easy to control, but not to cure; patients often experience a relapse after tapering of ASDs. Intermittent treatment with ASDs and the use of antacids as an escape medication may be an effective approach for managing patients with uncomplicated GERD and reducing the use of ASDs.15,16
There is little difference in the pattern of ASD prescribing for patients with ulcer, GERD, or functional dyspepsia. This similarity is particularly interesting because most studies of patients with functional dyspepsia have shown no benefit with the use of ASDs or with the eradication of H pylori.17-22 In these patients it may be sensible to taper the use of ASDs gradually, supported by antacid use; to explore the level of psychosocial distress; and to advise on lifestyle improvement.23 Long-term medication was prescribed as a preventive measure for the remaining 25% of all long-term users and to patients not given an endoscopy or barium study. The guidelines advise further investigation after several empirical treatments and again before a long-term ASD is prescribed.
One notable finding was that the patient’s sex appeared to influence whether investigations were ordered. The fact that ulcer disease is overall less often diagnosed in women might explain why the GPs did not perform further diagnostic investigations in women. Anxiety for endoscopy in men or women is another reason for not having a confirmed working diagnosis. A small number of anxious patients who have underlying ulcer disease might benefit from a test-and-treat approach to H pylori infection. However, serology cannot differentiate between either present or past H pylori infection and between ulcer or nonulcer disease.
Patients often experience a fast relapse of symptoms after discontinuation of therapy that may be related to rebound acid hypersecretion.24-26 It is possible that the prescription pattern of physicians in a subset of dyspeptic patients, especially in those with acid-related dyspepsia, leads to dependence on long-term therapy.
Conclusions
The use of ASDs, especially proton-pump inhibitors, is becoming increasingly common. In general practice in the Amsterdam region, 2% of patients used long-term ASDs. Patients with ulcer disease may stop taking ASDs after apparently successful H pylori eradication. Other patients require additional proof of underlying disease and H pylori status to determine the subsequent treatment approach. Tapering strategies in patients with mild reflux disease or functional dyspepsia need to be developed. Research is also needed in the general practice setting to develop strategies for tapering ASDs in chronic dyspeptic patients.
1. Lamberts H, Brouwer HJ, Mohrs J. Reason for encounter-, episode-and process-oriented standard output from Transition Project. Department of General Practice/Family Medicine. University of Amsterdam; 1991.
2. Numans ME, de Wit NJ, Geerdes RHM, et al. NHG-Standaard Maagklachten. Huisarts en Wetenschap 1993;36:375-9.
3. Omzet top 10 geneesmiddelen 1994. Data en Feiten Selectie, Stichting Farmaceutische Kengetallen, Den Haag; 1995.
4. Centrale Medische Pharmaceutische Commissie van de Ziekenfondsraad. Farmacotherapeutisch Kompas; 1995.
5. Ryder SD, O’Reilly S, Miller RJ, et al. Long-term acid suppressing treatment in general practice. BMJ 1994;308:827-30.
6. Goudie BM, McKenzie PE, Cipriano J, et al. Repeat prescribing of ulcer healing drugs in general practice—prevalence and underlying diagnosis. Aliment Pharmacol Ther 1996;10:147-50.
7. Numans ME, de Wit NJ, Geerdes RHM, et al. NHG-Standaard Maagklachten. Huisarts en Wetenschap 1996;39:565-77.
8. Van der Hulst RWM, Rauws EAJ, Köycu B, et al. Prevention of ulcer recurrence after eradication of H pylori infection: a prospective long-term follow-up study. Gastroenterology 1997;113:1082-6.
9. Hurenkamp GJB, Grundmeijer HGLM, van der Ende A, Tytgat GNJ, Assendelft WJJ, van der Hulst RWM. Arrest of chronic acid suppressant drug use after successful Helicobacter pylori eradication in patients with peptic ulcer disease: a six-month follow-up study. Aliment Pharmacol Ther 2001;15:1047-54.
10. Boyd EJ. The prevalence of esophagitis in patients with duodenal ulcer or ulcer-like dyspepsia. Am J Gastroenterol 1996;91:1539-43.
11. Meineche-Schmidt V, Rubin G, de Wit NJ. Helicobacter pylori infection: a comparative review of existing managment guidelines. Fam Pract 2000;17(suppl 2):S2-S5.
12. American Gastroenterological Association. Medical Position Statement: Evaluation of dyspepsia. Gastroenterology 1998;114:579-81.
13. Labenz J, Malfertheiner P. Helicobacter pylori in gastroesophageal reflux disease: causal agent, independent or protective factor? Gut 1997;41:277-80.
14. Labenz J, Tillenburg B, Peitz U, et al. Helicobacter pylori augments the pH-increasing effect of omeprazole in patients with duodenal ulcer. Gastroenterology 1996;110:725-32.
15. Bardhan KD, Müller-Lissner S, Bigard MA, et al. Symptomatic gastroesophageal reflux disease: double-blind controlled study of intermittent treatment with omeprazole or ranitidine. BMJ 1999;318:502-7.
16. Talley NJ, Lauritsen K, Tunturi-hihnala H, et al. Esomeprazole 20 mg maintains symptom control in endoscopy-negative gastroesophageal reflux disease: a controlled trial of “on-demand” therapy for 6 months. Aliment Pharmacol Ther 2001;15:347-54.
17. Talley NJ. A critique of therapeutic trials in Helicobacter pylori–postive functional dyspepsia. Gastroenterology 1994;106:1174-83.
18. Veldhuizen SJO, Cleary C, Talley NJ, et al. Drug treatment of functional dyspepsia: a systematic analysis of trial methodology with recommendations for design of future trials. Am J Gastroenterol 1996;4:660-73.
19. Laheij RJF, Jansen JBMJ, van de Lisdonk EH, et al. Review article: symptom improvement through eradication of H pylori in patients with non-ulcer dyspepsia. Aliment Pharmacol Ther 1996;10:843-50.
20. Blum AL, Talley NJ, O’Morain C, et al. Lack of effect of treating Helicobacter pylori infection in patients with nonulcer dyspepsia. N Engl J Med 1998;339:1875-81.
21. McColl K, Murray L, El-Omar E, et al. Symptomatic benefit from eradicating Helicobacter pylori infection in patients with nonulcer dyspepsia. N Engl J Med 1998;339:1869-74.
22. Talley NJ, Jansssens J, Lauritsen K, et al. Eradication of H pylori in functional dyspepsia: randomised double blind placebo controlled trial with 12 months’ follow up. BMJ 1999;318:833-7.
23. Quartero AO, Post MWM, Numans ME, et al. What makes the dyspeptic patient feel ill? A cross-sectional survey of functional health status, H pylori infection, and psychological distress in dyspeptic patients in general practice. Gut 1999;45:15-9.
24. El-Omar E, Banerjee S, Wirz BN, Penman I, Ardill JES, McColl KEL. Marked rebound acid hypersecretion after treatment with ranitidine. Am J Gastroenterology 1996;91:355-9.
25. Fullarton GM, McLauchlan G, McDonald A, Crean GP, McColl KEL. Rebound nocturnal hypersecretion after four weeks of treatment with an H2-receptor antagonist. Gut 1998;42:159-65.
26. Gillen D, Wirz AA, Ardill JE, McColl KE. Rebound acid hypersecretion after omeprazole and its relation to on-treatment acid suppression and Helicobacter pylori status. Gastroenterology 1999;116:239-47.
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17. Talley NJ. A critique of therapeutic trials in Helicobacter pylori–postive functional dyspepsia. Gastroenterology 1994;106:1174-83.
18. Veldhuizen SJO, Cleary C, Talley NJ, et al. Drug treatment of functional dyspepsia: a systematic analysis of trial methodology with recommendations for design of future trials. Am J Gastroenterol 1996;4:660-73.
19. Laheij RJF, Jansen JBMJ, van de Lisdonk EH, et al. Review article: symptom improvement through eradication of H pylori in patients with non-ulcer dyspepsia. Aliment Pharmacol Ther 1996;10:843-50.
20. Blum AL, Talley NJ, O’Morain C, et al. Lack of effect of treating Helicobacter pylori infection in patients with nonulcer dyspepsia. N Engl J Med 1998;339:1875-81.
21. McColl K, Murray L, El-Omar E, et al. Symptomatic benefit from eradicating Helicobacter pylori infection in patients with nonulcer dyspepsia. N Engl J Med 1998;339:1869-74.
22. Talley NJ, Jansssens J, Lauritsen K, et al. Eradication of H pylori in functional dyspepsia: randomised double blind placebo controlled trial with 12 months’ follow up. BMJ 1999;318:833-7.
23. Quartero AO, Post MWM, Numans ME, et al. What makes the dyspeptic patient feel ill? A cross-sectional survey of functional health status, H pylori infection, and psychological distress in dyspeptic patients in general practice. Gut 1999;45:15-9.
24. El-Omar E, Banerjee S, Wirz BN, Penman I, Ardill JES, McColl KEL. Marked rebound acid hypersecretion after treatment with ranitidine. Am J Gastroenterology 1996;91:355-9.
25. Fullarton GM, McLauchlan G, McDonald A, Crean GP, McColl KEL. Rebound nocturnal hypersecretion after four weeks of treatment with an H2-receptor antagonist. Gut 1998;42:159-65.
26. Gillen D, Wirz AA, Ardill JE, McColl KE. Rebound acid hypersecretion after omeprazole and its relation to on-treatment acid suppression and Helicobacter pylori status. Gastroenterology 1999;116:239-47.