Further Evidence to Monitor Long-term Proton Pump Inhibitor Use

Hayes, Kaleen N; Nakhla, Nardine; Tadrous, Mina

doi:10.1001/jamanetworkopen.2019.16184

Cited by 14 publications

(12 citation statements)

References 10 publications

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“…In humans, inappropriate use of PPIs has been well documented and includes inadequate indications for use, inappropriate duration of treatment, and unclear instructions for discontinuation of the medication on an outpatient basis. It is estimated that up to 65% of human patients prescribed PPIs have no documented ongoing indication for use, 3 and it is possible that this number is underestimated given that PPIs are available over the counter. Furthermore, chronic PPI use has been associated with a number of adverse events including acute kidney injury, 10,11 osteoporotic fractures, 12 hypocobalaminemia, 13 hypomagnesemia, 14 and dementia 15 .…”

Section: Discussionmentioning

confidence: 99%

Evaluation of proton pump inhibitor administration in hospitalized dogs in a tertiary referral hospital

Duxbury

Sorah

Tolbert

2022

Veterinary Internal Medicne

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Background Although proton pump inhibitors (PPIs) are commonly administered to hospitalized dogs, prescribing patterns and appropriateness of use require continued investigation. Hypothesis/Objective Describe prescription patterns and appropriateness of use associated with PPIs in hospitalized dogs at a single tertiary care facility. We hypothesized that the majority of prescriptions would not comply with current guidelines for the rational use of acid suppressants. Animals Two hundred randomly selected hospitalized dogs. Methods Retrospective evaluation of the medical records associated with a randomly selected sample of hospitalized dogs that received PPIs between January 2013 and December 2018. Results A total of 12 610 dogs were admitted for first‐time hospitalization between January 2013 and December 2018. Forty percent of these dogs (5062/12610) were prescribed a PPI PO or IV. Of the 200 randomly selected records, an adequate indication for use was identified in 27% of dogs (54/200). Of the dogs surviving to discharge, 54% (95/175) were discharged with a PPI and 51.6% (49/95) of those were prescribed an inadequate dose. Conclusions and Importance Our findings support other studies in which the majority of PPI prescriptions for hospitalized dogs at a tertiary care hospital lacked an appropriate indication. Furthermore, analysis of the prescribing patterns of dispensed PPIs identified a frequent occurrence of dosages considered inadequate, raising concern for ineffective treatment even with appropriate indications of use. With growing concern of adverse effects associated with PPI and other acid suppressant administration in human and veterinary medicine, rational use of these medications following consensus guidelines should be emphasized and treatment should be reserved for dogs with historical, physical examination, clinicopathologic, and imaging findings supportive of an appropriate indication for use.

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Section: Discussionmentioning

confidence: 99%

Evaluation of proton pump inhibitor administration in hospitalized dogs in a tertiary referral hospital

Duxbury

Sorah

Tolbert

2022

Veterinary Internal Medicne

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“…Asking patients about all medications taken, including over-the-counter drugs, and understanding why a patient is using a PPI are imperative to identifying deprescribing needs. For patients with a documented indication of PPI use, clinicians should ensure that the expected benefits are balanced against the risks of PPI therapy, and that the lowest effective dose is used for the shortest recommended duration [ 17 ].…”

Section: Discussionmentioning

confidence: 99%

Proton Pump Inhibitors are Risk Factors for Viral Infections: Even for COVID-19?

2020

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During the ongoing pandemic of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), more attention should be paid to the balance of risks and benefits associated with proton pump inhibitors for the following reasons. One of the main functions of gastric juice is to inactivate swallowed microorganisms, thereby inhibiting infectious agents from reaching the intestine. Studies have documented that proton pump inhibitors are a risk factor for rotavirus, influenza virus, norovirus, and Middle East respiratory syndrome coronavirus infections, and are associated with an increased risk of acute gastroenteritis during periods of highest circulation of enteric viruses. In light of the evidence for gastrointestinal infection implying a fecal–oral transmission of SARS-CoV-2 and given the magnitude of the SARS-CoV-2/coronavirus disease 2019 pandemic, associated with the widespread misuse of proton pump inhibitors, this suggests that we should not rule out the hypothesis that patients treated with proton pump inhibitors may be more at risk of being infected by SARS-CoV-2.

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“…This phenomenon is largely due to their effectiveness in the management of acid-related diseases such as gastroesophageal reflux disease (GERD), peptic ulcer, gastrointestinal bleeding, and Helicobacter pylori infection and the prevention of gastric ulcers in patients on aspirin or non-steroidal anti-inflammatory drugs [ 2 ]. Presumed safe, PPIs have been available over the counter since 2003, and previous data reported a significant amount of off-label PPI use, with up to 65% of prescriptions having no appropriate indication in the United States [ 3 ]. Omeprazole alone was dispensed more than 70 million times in 2016 [ 3 ], and PPIs account for over $10 billion in health care costs, with a global cost exceeding $25 billion per year [ 4 ].…”

Section: Introductionmentioning

confidence: 99%

“…Presumed safe, PPIs have been available over the counter since 2003, and previous data reported a significant amount of off-label PPI use, with up to 65% of prescriptions having no appropriate indication in the United States [ 3 ]. Omeprazole alone was dispensed more than 70 million times in 2016 [ 3 ], and PPIs account for over $10 billion in health care costs, with a global cost exceeding $25 billion per year [ 4 ]. Moreover, rebound acid hypersecretion may occur after stopping PPI therapy, leading to the recurrence of gastric symptoms and thus to drug dependency [ 5 ].…”

Section: Introductionmentioning

confidence: 99%

“…This PPI overuse raises concerns about the potential risks it could cause, especially in the elderly affected by multiple comorbidities and taking multiple medications [ 6 ]. Indeed, recent studies, mostly observational studies, reported various adverse events related to long-term PPI therapy, including the risks of cardiovascular diseases [ 7 ], fractures, pneumonia, Clostridium difficile infection, impaired absorption of micronutrients, kidney disease, dementia, gastric neoplasia [ 4 , 8 ], and drug-to-drug interactions [ 3 ]. Regarding the cardiovascular risk, the concomitant use of clopidogrel and PPIs has been specifically investigated in several studies as clopidogrel and PPIs are both metabolized by the cytochrome P450 isoenzyme 2C19, leading to drug–drug interaction due to competition at the binding site [ 9 ].…”

Section: Introductionmentioning

confidence: 99%

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The Safety of Long-Term Proton Pump Inhibitor Use on Cardiovascular Health: A Meta-Analysis

Jeridi

Pellat

Ginestet

et al. 2022

JCM

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Introduction: Proton pump inhibitors (PPIs) are one of the most prescribed classes of drugs worldwide as a first-line treatment of acid-related disorders. Although adverse effects are rare and rapidly reversible after a short exposure, concerns have been recently raised about a greater toxicity on cardiovascular health after a longer exposure, especially when combined with clopidogrel. We aimed to evaluate the safety of long-term PPI use on cardiovascular health in patients with known atheromatous cardiovascular disease. Methods: A literature search was conducted in the PubMed, Embase, and Cochrane Library databases and grey literature in April 2022. Articles published between 2014 and 2022 were considered relevant if they were designed as randomized controlled trials (RCTs) that included post hoc analyses or prospective observational studies and if they investigated clinical cardiovascular outcomes associated with PPI use for 6 months or more in patients suffering from cardiovascular disease requiring antiplatelet agent therapy and/or coronary angioplasty. Statistical analyses were performed using RevMan 5.4 software (Computer program, the Cochrane Collaboration, 2020, London, UK). The risk of bias was assessed using the Cochrane risk-of-bias tool for the RCTs and the Newcastle–Ottawa scale for the observational studies. Results: A total of 10 full-text articles involving 53,302 patients were included. Substantial heterogeneity was found among the 10 included studies. The primary analysis showed no significant differences between the PPI group and the control group for the risks of major adverse cardiovascular events (MACEs), all-cause death (ACD), or target vessel revascularization (TVR) using a random-effects model (OR 1.15, 95% CI 0.98–1.35, p = 0.08, I2 = 73%; OR 1.24, 95% CI 0.94–1.65, p = 0.13, I2 = 63%; and OR 1.19, 95% CI 0.76–1.87, p = 0.45, I2 = 61%, respectively). The primary analysis yielded similar results for the risks of myocardial infarction (MI), stroke, and cardiovascular death (CVD) using a fixed-effects model (OR 0.98, 95% CI 0.88–1.09, p = 0.66, I2 = 0%; OR 1.02, 95% CI 0.90–1.17, p = 0.73, I2 = 0%; and OR 1.04, 95% CI 0.94–1.16, p = 0.44, I2 = 35%, respectively). Likewise, a subgroup analysis based on eight randomized controlled trials failed to identify any association between PPI use and the risks of MACEs, MI, stroke, TVR, ACD, or CVD using a fixed-effects model (overall pooled OR 1.01, 95% CI 0.96–1.06; p = 0.66; I2 = 0%). The pulled data from the two included observational studies (OS) demonstrated a significantly increased risk of MACEs in the PPI group (OR 1.42, 95% CI [1.29–1.57], p <0.001; I2 = 0%). In another subgroup analysis, no evidence of an increased risk of adverse cardiovascular events in the co-therapy PPI/clopidogrel versus clopidogrel alone groups was found with the exception of the risk of ACD (OR 1.50, 95% CI 1.23–1.82, p = 0.001, I2 = 0%). Nevertheless, after performing a sensitivity analysis reaching heterogeneity I2 = 0%, the co-prescription of PPIs and clopidogrel was at increased risk of MACEs (p < 0.001), CVD (p = 0.008), and TVR (p < 0.001) but remained statistically non-significant for the risk of MI (p = 0.11). Conclusions: The overall results of this meta-analysis showed that long-term PPI use was not associated with an increased risk of adverse cardiovascular events. However, inconsistent results were found for combined PPI/clopidogrel therapy. These results should be considered with caution in light of the significant heterogeneity, the limited number of included studies, and the lack of adjustment for potential confounders.

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Further Evidence to Monitor Long-term Proton Pump Inhibitor Use

Cited by 14 publications

References 10 publications

Evaluation of proton pump inhibitor administration in hospitalized dogs in a tertiary referral hospital

Evaluation of proton pump inhibitor administration in hospitalized dogs in a tertiary referral hospital

Proton Pump Inhibitors are Risk Factors for Viral Infections: Even for COVID-19?

The Safety of Long-Term Proton Pump Inhibitor Use on Cardiovascular Health: A Meta-Analysis

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