Introduction
Proton pump inhibitors (PPIs) are commonly prescribed drugs in preventing and treating certain conditions for definite time periods. However, evidence suggests an association of wide range of adverse effects with unwarranted and incongruous sustained PPI use1. Inappropriate PPI use is also triggered by physicians who advocate PPIs without an actual indication. In ambulatory settings, PPI overuse frequently occurs due to inadequate practice of on-demand and step-down therapy or failure to reconsider the need for therapy continuation. Redundant continuation of treatment is also a result of insufficient, repetitive endorsements of PPIs at discharge or maintenance of PPI therapy by primary care physicians without appropriate evaluation. This compounds towards the financial burden of an individual and exposes them to the adverse effects2,3.
Physicians tend to display little knowledge and awareness concerning PPI usage which may lead to over-prescription. Good clinical practice entails prescribing guidelines and awareness programs for staff4. A rational approach towards safe and effective PPI therapy encompasses provider awareness concerning best practice guidelines on the use of PPIs and disseminating pertinent education to individuals. Provider- and patient-education, accompanied by stewardship and motivation, are fundamental to the pertinent use of PPIs for the appropriate indications1. Awareness and knowledge of risks associated with the use of PPIs persuade physicians to ensure apt dosing and duration of PPI therapy, along with long-term monitoring strategies in patients with risk factors and comorbidities5. Disparities in prescribing PPIs appears to pivot not around discrepancies in knowledge but around physician attitudes and self-justified perceptions6.
When not indicated, subsequent to patient discussion, attempts to deprescribe the PPI could be considered. Deprescribing approaches comprise of reducing or stopping the drug, or employing “on-demand” therapy after completion of treatment course for a definite indication1, or shifting from PPI to H2-receptor blockers. In order to encourage changes to resistance of primary care providers’, peer-led education and coaching could aid in practice7. This prospective survey was carried out in India, with a primary aim to assess the knowledge and perceptions of PPI-related adverse events among physicians, and subsequent change in behaviour associated with the use of PPIs.
Methods
This was a prospective, questionnaire-based, multicentric survey with data collected from physicians across North and South India who volunteered to participate in periodic surveys. The questionnaire was administered to 810 physicians through email, of which 465 responded.
Ethics Statement
This study was performed according to the principles of the Declaration of Helsinki. The study protocol was approved by the Institutional Ethical Committee of AIG hospitals, Hyderabad, (IEC Registration ECR/346/Inst/AP/2013/RR-22), DCGI registered, NABH accredited (Approval Identification Code: AIG/IEC-BH&R30/11.2022.01). All participants have given a formal written informed consent for being included in the study.
Survey Questionnaire
This questionnaire was adopted with permission from Kurlander JE et al8 and adapted to suit the Indian population (Supplementary Material). Participants were initially asked to provide basic demographic, professional and practice characteristics, familiarity with guidelines on appropriate use of PPI and availability of decision support to help with appropriate practice of PPI discontinuation. The survey comprised of questions with multiple choice answers about general familiarity with concern about possible PPI associated adverse effects, awareness and beliefs about adverse effects, indications to continue and deprescribe PPI.
The physicians were also questioned regarding the extent to which they changed their prescribing habits as a result of adverse effects noticed with PPI use. The participant physicians were provided with four commonly encountered clinical case scenarios of patients with upper gastrointestinal bleed (UGIB) and the grading was from minimal to high, based on the risk of severe bleed. Grading of severity was as follows,
1. Minimal [history of gastroesophageal reflux disease {GERD}],
2. Low [low-dose aspirin],
3. Moderate [low dose aspirin and warfarin] and
4. High [prior peptic ulcer disease and low dose aspirin] (Figure 1).
Following each scenario, they were inquired to provide their recommendations on management of the PPI prescription with response options ranging from 1) continue omeprazole, 2) stop omeprazole or 3) stop omeprazole and start H2 blocker. In the high-risk UGIB-prevention scenario, participant physicians were asked about the extent of effectiveness they believed omeprazole was at reducing the risk of UGIB on the Likert-type scale (not at all/slightly/ moderate/extremely important).
Statistical Analysis
Categorical variables were calculated using descriptive statistics, and included frequencies and percentages. While computing the frequency of awareness and beliefs about adverse effects, osteoporosis, osteopenia and bone fracture were combined under the ‘bone loss or fracture’ category. Data were presented graphically wherever deemed necessary. Data from the surveys were input and analysed using MS Excel and GraphPad softwares.
Results
Sample Characteristics
Out of the 810 questionnaires administered, the survey was completed by a total of 465 physicians. The participant characteristics are outlined in Table 1.
All the survey participants were Internal Medicine specialists. Minority of the survey takers (0.65%; 3/465) completed their residency in internal medicine between 1960 and 1979, while 48.60% (226/465) completed it during 1980 and 1999, and 50.75% (236/465) completed it between 2000 and 2019. About 28% (130/465) participants agreed regarding the availability of decision support systems in practice to help with appropriate continuation or discontinuation of PPIs. Nearly 37% i.e., 169/465, took PPI themselves at least once weekly.
Perceptions and Experience with PPIs
Most respondents reported very little familiarity with published data on PPI adverse effects (50.11%), majority were slightly concerned about adverse effects when prescribing PPIs (56.77%), with 48.17% having somewhat changed their prescribing practices for PPIs on account of these adverse effects (Table 2). Figure 2 illustrates survey participants’ beliefs on whether PPIs increase the risk of specific adverse effects; a significant proportion of physicians were unaware of the specific adverse effects with PPI use.
Concern About Adverse Effects
When the participants were asked which one of the possible adverse effects they were clinically worried about when prescribing PPIs, the most common response was bone loss or fracture (29.46%; 137/465), followed by pneumonia (16.56%; 77/465), acute interstitial nephritis (9.03%; 42/465), vitamin B12 deficiency (8.17%; 38/465), gastric cancer (6.67%; 31/465), Clostridioides difficile infection (6.45%; 30/465), chronic kidney disease (5.38%; 25/465), vitamin D deficiency (3.87%; 18/465), heart attack (2.37%; 11/465), dementia (1.08%; 5/465) and stroke (0.86%; 4/465). Nearly 10.11% (47/465) of the respondents had an exclusive response that included none of these adverse effects.
Management of Patient Scenarios and Perceived Effectiveness of PPis for UGIB Prevention
Considering the history of GERD in Scenario 1, more than half (52%) of the physicians opted stopping the omeprazole. While most (47%) physicians considered preventing recurrence of GERD symptoms to be of intermediate importance, 36% did not consider the risk of bone fracture to be important in taking a decision.
In response to Scenarios 2 and 3, majority of the physicians (46.67% and 48.82%, respectively) recommended continuing the PPI. Nearly 20% suggested stopping the PPI completely while about 30% responded with replacing the PPI with an H2-blocker in both the scenarios.
For Scenario 4, >50% of participants recommended continuation of the PPI, only 15% suggested stopping the PPI, and 31.4% preferred replacing the PPI with H2-blocker. 43% respondents considered preventing recurrence of GERD symptoms to be extremely important; 34% thought that the risk of bone fracture was of moderate importance in making a decision. (Figure 3; Table 3).
More than half (55.48%) survey responders perceived the PPI to be moderately effective at reducing the risk of UGIB, whereas 26.45% believed it was slightly effective, 16.56% as very effective, and 1.51% felt it was not at all effective. When asked about their recommendation regarding omeprazole change if they knew with certainty that (a) the patient’s risk of UGIB is 2.7% per year, and use of a PPI can reduce this risk to 1.1% per year, (b) her risk of hip fracture is 1.0% per year, and omeprazole increases the risk to 1.3% per year, 59.35% (276/465) physicians responded that they would change the PPI, while the remaining 40.65% (189/465) denied any change in PPI. Majority (65.81%; 306/465) respondents recommended that they would continue the PPI, 9.68% (45/465) advocated stopping the PPI, whereas 24.52% (114/465) preferred replacing the PPI with an H2 blocker.
Discussion
Physicians tend to exhibit little knowledge and poor adherence to recommendations concerning PPI prescription4. A qualitative study by Wermeling M et al aimed to identify motives and factors linked to the continuation of incongruous PPI prescriptions in primary care. Semi-structured qualitative interviews were carried out in five general practitioners who frequently continued inappropriate drug therapy with PPIs and compared them to five other general practitioners who often discontinued inappropriate PPI prescriptions. The authors found differences between continuing and discontinuing general practitioners in their level of knowledge, perceptions of their competence as well as the threshold to prescribing PPIs in hospitals. Most practitioners assumed that PPIs were nearly free of side effects; in fact some even considered them a ‘wonder weapon’ against a range of gastrointestinal symptoms9.
Padhy BM et al conducted a survey, using a two-page questionnaire, on the use of PPIs, in order to evaluate the knowledge, attitude, and preferences of resident doctors in an emergency care setup in India. About 44% residents were aware of the decrease in absorption of vitamin B12 with PPI use, 22% of the higher risk of C. difficile infection, 12% of the increased hip fracture risk and a mere 10% of the increased risk of community-acquired pneumonia10. In an online survey assessing internists’ perceptions of PPI adverse effects and its impact on prescribing practices, 99% reported ‘at least some familiarity’ with reported adverse effects (mean, 4.9±1.0), while 98% reported ‘at least some concern’ (4.6±1.3). Furthermore, 92% reported making ‘at least some change’ in their prescribing practices (i.e. score >1; 4.2±1.5). A total of 63% respondents reported reducing the PPI dose ‘sometimes or often’, 52% preferred switching to H2 blocker, whereas 44% discontinued the use of PPI. Nearly 85% internists were aware of bone loss as a possible PPI adverse effect, 73% of pneumonia, and 68% of bowel infection (p<0.001)11.
A descriptive-analytical study was conducted by Luo H et al on 900 medical staff, which included 300 doctors, 300 nurses and 300 pharmacists, in China; of these 851 valid questionnaires from 295 doctors, 268 nurses and 288 pharmacists were returned and analysed. The score evaluating PPI awareness of medical staff was recorded to be ‘low’ (59.47 ± 15.75). They found significantly higher levels of awareness as well as in terms of attitude towards the use of PPIs among pharmacists compared to doctors and nurses (p<0.01). The researchers highlighted the lack of awareness relating to rational use of PPI in China among medical staff. They advocated the necessity to call for action on improving PPI awareness and medication-taking behaviours in order to moderate PPI overuse and promote rationality of PPI application12.
In India, Ghosh G and colleagues conducted a prospective observational, survey, by administering a 20-item questionnaire to 83 physicians in primary care and specialty clinics relating to knowledge of PPI-related adverse events and management of patients on PPIs. About 60% respondents reported concern towards PPI-related adverse events, with the most frequently reported being osteoporosis (49%) and bone fractures (46%). Based on their concerns, 37% physicians reported changing their practice13.
A similar survey by Kurlander JE et al was conducted at a national level to estimate 799 internists’ perceptions of PPI-related adverse effects and self-reported clinical use. Similar to our study findings, the mean age of the internists included was 48±12 years, with the majority being males (64.1%). Approximately 77.1% interns visited outpatients in clinic, compared to 95% of our survey respondents. Per week, while 1-25 patients were seen by 17.6% interns, 26-50 patients by 27.5% interns, 51-75 patients by 26.1% interns, 76-100 patients by 20.1% interns and >100 patients by 8.7% interns, 51% of our physicians consulted >100 patients weekly. A substantial, 67.5% of physicians spent 75%-100% of time in patient care, most (66%) physicians in our survey spent 26%-49% of their time in patient care. Analogous to our findings, most of them were part of either academic practice (28%) or group practice (29%). Contrary to our observations where only 39% physicians reported familiarity with guidance on appropriate PPI use to prevent gastrointestinal bleeding, their study reported a higher proportion (67%); only 22% internists’ reported availability of decision support to help with apt continuation or discontinuation of PPIs. The researchers found that 70% physicians were ‘somewhat/very concerned’ about adverse effects associated with PPI use, and 76% changed their prescribing ‘somewhat/very much’. Majority believed that PPIs increase the risk for 6 out of the 12 queried adverse effects. Most respondents (93%) reported being ‘somewhat/very familiar’ with published data on PPI-related adverse effects, about 70% were ‘somewhat/very concerned’ about adverse effects while prescribing PPIs, and >75% ‘somewhat/very much’ changed their prescribing practices. Just >50% physicians perceived PPIs to be ‘somewhat/very effective’ in preventing UGIB. A disparity from our study findings was that 86% physicians recommended PPI discontinuation in a GERD scenario, and 79% recommended discontinuation in a high-risk UGIB prevention scenario. In the high-risk UGIB scenario, the physicians’ perceived effectiveness for bleeding prevention was found to be strongly associated with continuing PPI (odds ratio, 7.68; p<0.001 for ‘moderately effective’; odds ratio, 17.3; p<0.001 for ‘very effective’). Though the frequency was low in our study, the greatest proportion by Kurlander JE et al reported awareness of bone loss or fracture (96%), C. difficile infection (93%), and pneumonia (90%), followed by awareness of B12 deficiency (82%), chronic kidney disease (72%), vitamin D deficiency (70%), acute interstitial nephritis (70%), gastric cancer (68%), dementia (68%), death (63%), heart attack (61%), and stroke (58%). The respondents validated the belief that PPIs intensify the risk for a mean of 5.2 (SD 2.5) different conditions (bone loss or fracture, 88%; C. difficile infection, 82%; and pneumonia, 70% 8.
A clear causal relationship has not yet been demonstrated, but abuse of PPI should be avoided as studies on PPI-related side effects continue to be published14,15. Pneumonia continues to remain a common cause of hospital admission, morbidity as well as mortality. It is hence judicious to curtail any additional risk of pneumonia by circumventing inappropriate use of PPIs16. Nonetheless, it is not prudent to avoid PPIs in patients who have demonstrated evident benefits of prescription drugs.
Conclusion
There is a need for strategies to alter behaviour based on a physicians’ awareness of non-steroidal anti-inflammatory drug (NSAID) risks, indications for PPIs, besides prescribing approaches in hospitals. Healthcare practitioners could benefit from explicit guidance about scenarios in which patients can safely discontinue the use of PPIs, and regarding strategies for de-escalation that are most likely to succeed. There should be a strong foundation for prescribing PPIs, and a balanced regime to be followed for only as long as essential, at the lowest effective dose avoiding avertible prescriptions.
Forthcoming interventions must emphasise on ascertaining appropriate prescription of PPIs tailored to individual benefits and risks.
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