Trends Cardiovasc Med. 2018 Oct 21. pii: S1050-1738(18)30243-3. doi: 10.1016/j.tcm.2018.10.008. [Epub ahead of print]
Cardiovascular and non-cardiovascular concerns with proton pump inhibitors: Are they safe?
Corsonello A1, Lattanzio F2.
Author information
1
Italian National Research Center on Aging (IRCCS INRCA), Ancona, Cosenza, Italy. Electronic address: andrea_corsonello@tin.it.
2
Italian National Research Center on Aging (IRCCS INRCA), Ancona, Cosenza, Italy.
Abstract
The introduction of proton pump inhibitors (PPIs) has been a cornerstone in the treatment of acid-related disorders, such as gastroesophageal reflux and peptic ulcer, and their use has increased rapidly during the last decades. Being highly lipophilic drugs, they may potentially affect several pathophysiological pathways involved in cardiovascular and kidney morbidity, immune response and infections, absorption of selected nutrients, bone metabolism and cognitive function. Clinical epidemiology evidence coming from well-designed analyses of observational data consistently reported that long-term use of PPIs may increase the risk of cardiovascular events among patients treated with thienopyridines, tubular-interstitial nephritis and chronic kidney disease, hypomagnesemia, and fractures. Conversely, currently available evidence about the impact of PPIs on cardiovascular risk among patients not treated with thienopyridines, infections, nutritional disorders, cognitive impairment and dementia is limited by confounding. Given that randomized controlled trials investigating these issues are unlikely to be realized, the application of modern pharmacoepidemiology principles is expected to mitigate limitations of observational studies while addressing these relevant knowledge gaps. Meanwhile, physicians should be aware of potential issues related to long-term use of PPIs and weigh benefits of PPI therapy for appropriate indications along with the likelihood of the potential risks. A deprescription trial should be considered for all PPI users who do not have definite indications for long-term therapy.
Copyright © 2018 Elsevier Inc. All rights reserved.
KEYWORDS:
Clinical pharmacology; Proton pump inhibitors; Safety
PMID: 30389278 DOI: 10.1016/j.tcm.2018.10.008
Drug Saf. 2018 Dec;41(12):1387-1396. doi: 10.1007/s40264-018-0704-9.
Proton Pump Inhibitor Use and Risk of Developing Alzheimer's Disease or Vascular Dementia: A Case-Control Analysis.
Imfeld P1,2, Bodmer M3, Jick SS4,5, Meier CR6,7,8.
Author information
1
Basel Pharmacoepidemiology Unit, Division of Clinical Pharmacy and Epidemiology, Department of Pharmaceutical Sciences, University of Basel, Basel, Switzerland.
2
Hospital Pharmacy, University Hospital Basel, Basel, Switzerland.
3
Medical Clinic, Zuger Kantonsspital, Baar, Switzerland.
4
Boston Collaborative Drug Surveillance Program, Lexington, MA, USA.
5
Department of Epidemiology, Boston University School of Public Health, Boston, MA, USA.
6
Basel Pharmacoepidemiology Unit, Division of Clinical Pharmacy and Epidemiology, Department of Pharmaceutical Sciences, University of Basel, Basel, Switzerland. christoph.meier@usb.ch.
7
Hospital Pharmacy, University Hospital Basel, Basel, Switzerland. christoph.meier@usb.ch.
8
Boston Collaborative Drug Surveillance Program, Lexington, MA, USA. christoph.meier@usb.ch.
Abstract
INTRODUCTION:
Long-term use of proton pump inhibitors (PPIs) has been associated with an increased risk of Alzheimer's disease (AD) in observational studies. The role of exposure duration, and whether this applies to other dementia subtypes, has not been explored in these studies.
OBJECTIVE:
The aim was to study the association between long-term use of PPIs (or of histamine-2 receptor antagonists [H2RAs], as a negative control) and the risk of developing AD or vascular dementia (VaD).
METHODS:
We conducted a case-control analysis on the UK-based Clinical Practice Research Datalink (CPRD). We identified 41,029 patients aged ≥ 65 years with newly diagnosed AD or VaD between 1998 and 2015 and matched them 1:1 to dementia-free controls on age, sex, calendar time, general practice, and number of years of recorded history. We applied conditional logistic regression analyses to calculate adjusted odds ratios (aORs), with 95% confidence intervals (CIs), of developing AD or VaD in relation to previous use of PPIs or H2RAs, categorized by exposure duration.
RESULTS:
As compared to non-use, long-term PPI use (≥ 100 prescriptions) was not associated with an increased risk of developing AD (aOR 0.88, 95% CI 0.80-0.97) or VaD (aOR 1.18, 95% CI 1.04-1.33). Neither was long-term use of H2RAs (≥ 20 prescriptions) associated with an increased risk of developing AD (aOR 0.94, 95% CI 0.87-1.02) or VaD (aOR 0.99, 95% CI 0.89-1.10).
CONCLUSION:
In this large, case-control analysis, we did not find any evidence for an increased risk of either AD or VaD related to PPI or H2RA use.
Comment in
Comment on "Proton Pump Inhibitor Use and Risk of Developing Alzheimer's Disease or Vascular Dementia: A Case-Control Analysis". [Drug Saf. 2018]
Authors' Reply to Katsuhiro Toda's Comment on "Proton Pump Inhibitor Use and Risk of Developing Alzheimer's Disease or Vascular Dementia: A Case-Control Analysis". [Drug Saf. 2018]
PMID: 30146658 DOI: 10.1007/s40264-018-0704-9
Cardiovascular and non-cardiovascular concerns with proton pump inhibitors: Are they safe?
Corsonello A1, Lattanzio F2.
Author information
1
Italian National Research Center on Aging (IRCCS INRCA), Ancona, Cosenza, Italy. Electronic address: andrea_corsonello@tin.it.
2
Italian National Research Center on Aging (IRCCS INRCA), Ancona, Cosenza, Italy.
Abstract
The introduction of proton pump inhibitors (PPIs) has been a cornerstone in the treatment of acid-related disorders, such as gastroesophageal reflux and peptic ulcer, and their use has increased rapidly during the last decades. Being highly lipophilic drugs, they may potentially affect several pathophysiological pathways involved in cardiovascular and kidney morbidity, immune response and infections, absorption of selected nutrients, bone metabolism and cognitive function. Clinical epidemiology evidence coming from well-designed analyses of observational data consistently reported that long-term use of PPIs may increase the risk of cardiovascular events among patients treated with thienopyridines, tubular-interstitial nephritis and chronic kidney disease, hypomagnesemia, and fractures. Conversely, currently available evidence about the impact of PPIs on cardiovascular risk among patients not treated with thienopyridines, infections, nutritional disorders, cognitive impairment and dementia is limited by confounding. Given that randomized controlled trials investigating these issues are unlikely to be realized, the application of modern pharmacoepidemiology principles is expected to mitigate limitations of observational studies while addressing these relevant knowledge gaps. Meanwhile, physicians should be aware of potential issues related to long-term use of PPIs and weigh benefits of PPI therapy for appropriate indications along with the likelihood of the potential risks. A deprescription trial should be considered for all PPI users who do not have definite indications for long-term therapy.
Copyright © 2018 Elsevier Inc. All rights reserved.
KEYWORDS:
Clinical pharmacology; Proton pump inhibitors; Safety
PMID: 30389278 DOI: 10.1016/j.tcm.2018.10.008
Drug Saf. 2018 Dec;41(12):1387-1396. doi: 10.1007/s40264-018-0704-9.
Proton Pump Inhibitor Use and Risk of Developing Alzheimer's Disease or Vascular Dementia: A Case-Control Analysis.
Imfeld P1,2, Bodmer M3, Jick SS4,5, Meier CR6,7,8.
Author information
1
Basel Pharmacoepidemiology Unit, Division of Clinical Pharmacy and Epidemiology, Department of Pharmaceutical Sciences, University of Basel, Basel, Switzerland.
2
Hospital Pharmacy, University Hospital Basel, Basel, Switzerland.
3
Medical Clinic, Zuger Kantonsspital, Baar, Switzerland.
4
Boston Collaborative Drug Surveillance Program, Lexington, MA, USA.
5
Department of Epidemiology, Boston University School of Public Health, Boston, MA, USA.
6
Basel Pharmacoepidemiology Unit, Division of Clinical Pharmacy and Epidemiology, Department of Pharmaceutical Sciences, University of Basel, Basel, Switzerland. christoph.meier@usb.ch.
7
Hospital Pharmacy, University Hospital Basel, Basel, Switzerland. christoph.meier@usb.ch.
8
Boston Collaborative Drug Surveillance Program, Lexington, MA, USA. christoph.meier@usb.ch.
Abstract
INTRODUCTION:
Long-term use of proton pump inhibitors (PPIs) has been associated with an increased risk of Alzheimer's disease (AD) in observational studies. The role of exposure duration, and whether this applies to other dementia subtypes, has not been explored in these studies.
OBJECTIVE:
The aim was to study the association between long-term use of PPIs (or of histamine-2 receptor antagonists [H2RAs], as a negative control) and the risk of developing AD or vascular dementia (VaD).
METHODS:
We conducted a case-control analysis on the UK-based Clinical Practice Research Datalink (CPRD). We identified 41,029 patients aged ≥ 65 years with newly diagnosed AD or VaD between 1998 and 2015 and matched them 1:1 to dementia-free controls on age, sex, calendar time, general practice, and number of years of recorded history. We applied conditional logistic regression analyses to calculate adjusted odds ratios (aORs), with 95% confidence intervals (CIs), of developing AD or VaD in relation to previous use of PPIs or H2RAs, categorized by exposure duration.
RESULTS:
As compared to non-use, long-term PPI use (≥ 100 prescriptions) was not associated with an increased risk of developing AD (aOR 0.88, 95% CI 0.80-0.97) or VaD (aOR 1.18, 95% CI 1.04-1.33). Neither was long-term use of H2RAs (≥ 20 prescriptions) associated with an increased risk of developing AD (aOR 0.94, 95% CI 0.87-1.02) or VaD (aOR 0.99, 95% CI 0.89-1.10).
CONCLUSION:
In this large, case-control analysis, we did not find any evidence for an increased risk of either AD or VaD related to PPI or H2RA use.
Comment in
Comment on "Proton Pump Inhibitor Use and Risk of Developing Alzheimer's Disease or Vascular Dementia: A Case-Control Analysis". [Drug Saf. 2018]
Authors' Reply to Katsuhiro Toda's Comment on "Proton Pump Inhibitor Use and Risk of Developing Alzheimer's Disease or Vascular Dementia: A Case-Control Analysis". [Drug Saf. 2018]
PMID: 30146658 DOI: 10.1007/s40264-018-0704-9
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