PPIs NOT Linked to Cognitive Decline/Dementia & PPIs NOT Linked to Heart Attacks

In a prospective study (M Wod et al. Clin Gastroenterol Hepatol 2018; 16: 681-89), data on middle-aged (n=2346, 46-67 yrs) and older individuals (n=2475) were collected in the Longitudinal Study of Aging Danish Twins.  This study showed that there was no difference in cognitive decline between PPI users and non-users.

The second study (SN Landi et al. Gastroenterol 2018; 154: 861-73) used a large administrative database and reviewed more than 5 million new  users of prescription PPIs and prescription H2RAs.  The authors found no significant difference in myocardial infarctions (MIs) between PPIs and H2RAs over a 12 month period.

Related blog posts:

Preterm Infants with Increased Infections Following Acid Suppression Therapy

A recent study (P Manzoni et al. J Pediatr 2018; 193: 62-7) provide more data on the detrimental effects of gastric acid inhibitors (eg. proton pump inhibitors, histamine-2 receptor antagonists).  This study was a secondary analysis using prospectively collected data from 235 preterm very low birth weight infants. Key findings:

  • “After multivariate analysis, exposure to inhibitors of gastric acidity remained significantly and independently associated with LOS [late-onset sepsis] (OR 1.03); each day of inhibitors of gastric acidity exposure conferred an additional 3.7% odds of developing LOS.”
  • Acid suppression therapy was associated with gram-negative (P<.001) and fungal pathogens (P=.001)
  • The study showed an association between acid blockers and with necrotizing enterocolitis, which was mitigated in those who received bovine lactoferrin

My take (borrowed, in part, from authors): This data “confirm, strengthen, and expand on previous reports describing an association between inhibitors of gastric acidity and infections.”  Thus, the risks of these medications is likely greater than the benefits in the majority of preterm infants.

Related blog posts:

Bright Angel Trail

#NASPGHAN17 Annual Meeting Notes (Part 2): Year in Review

This blog entry has abbreviated/summarized this presentation. Though not intentional, some important material is likely to have been omitted; in addition, transcription errors are possible as well.

This first slide shows the growth in NASPGHAN membership:

Year in Review

Melvin Heyman  Editor, JPGN

This lecture reviewed a number of influential studies that have been published in the past year.  After brief review of the study, Dr. Heyman summarized the key take-home point.

 

AGA Blog: What are the complications of PPI Therapy?

AGA Journals Blog: What are the complications of proton pump inhibitor (PPI) Therapy?

The blog post reviews a recent article on PPIs and potential complications.

An excerpt:

review article from Michael F. Vaezi et al discusses potential adverse consequences of proton-pump inhibitor (PPI) therapy in the July issue of Gastroenterology…(2017; 153: 35-48). The authors discuss overzealous conclusions based on weak associations that have caused widespread alarm, leading to inappropriate discontinuation of a medicine that is needed for an established disease process. They present absolute and relative risks for adverse effects associated with long-term use of PPIs…

Vaezi et al review the consistency of proposed associations with PPI use and the time period between the PPI exposure and outcome, and the effects of different doses. They provide guidance for methodologies of future studies.

The review article concludes that PPIs have revolutionized the management of patients with GERD and patients at risk of upper gastrointestinal ulceration and bleeding from aspirin or NSAIDs. However, many patients receive PPIs unnecessarily for conditions or symptoms for which they would not have been expected to provide benefit… Vaezi et al state that, as always, PPIs should be given in the lowest effective dose, for the shortest possible time.

They add that much of the evidence linking PPI use to serious long-term adverse consequences is weak and insubstantial. It should not deter prescribers from using appropriate doses of PPIs for appropriate indications.

Full text of original article: Complications of Proton Pump Inhibitor Therapy

Table 6 lists the strengths of the findings along with other Hill Criteria to assess all of the proposed complications.  The vast majority of potential complications have “weak” proof; the exceptions include bacterieal enteric infections/Clostridium difficile infection which have moderate strength of evidence and and fundic gland polyps which have high strength of evidence.

My take: This study and the associated AGA Journals blog post indicate that most of the reports of complications associated with PPI remain unproven and are based on weak evidence.

 

Recent Study Did NOT Find Dementia Risk with PPIs

When performing retrospective studies, many times a potential association can be found with medications or diet and specific problems.  When these risks/associations are low (i.e. relative risks <2), often, these findings do not hold up, particularly with prospective studies which are much more able to control for confounding variables.

For proton pump inhibitors (PPIs), many potential complications have been suggested at  low relative risk findings in poorly-controlled studies.  A recent study has contradicted previous findings suggesting that PPIs increase the risk of dementia.

Goldstein FC, et al. J Am Geriatr Soc. 2017;doi:10.1111/jgs.14956. (Thanks to Ben Gold for this reference)

A link and an excerpt from a summary of this study from Healio Gastroenterology:

Link: Study finds no link between PPIs, dementia, Alzheimer’s risk

Excerpt:

They evaluated 10,486 volunteers within the NIH-supported Alzheimer’s Disease Centers who were aged 50 years and older and had either normal cognition or mild cognitive impairment at baseline. Participants underwent neuropsychological evaluations and self-reported PPI use at two to six annual visits between 2005 and 2015.

Overall, 884 reported they were taking PPIs at every visit, 1,925 reported they took PPIs intermittently, and 7,677 never reported taking PPIs.

Those who reported continuous PPI use showed a lower risk for cognitive function decline compared with those who never reported using PPIs (HR = 0.78; 95% CI, 0.66-0.93) as well as a lower risk for developing mild cognitive impairment or Alzheimer’s disease (HR = 0.82; 95% CI, 0.69-0.98).

Those who reported using PPIs intermittently also showed a lower risk for cognitive function decline (HR = 0.84; 95% CI, 0.76–0.93) and for developing mild cognitive impairment or Alzheimer’s disease (HR = 0.82; 95% CI, 0.74–0.91).

My take: This study provides reassurance that PPIs are unlikely to result in cognitive decline. Particularly when a study suggests a low risk of an association, further studies are needed to clarify the true risks.

Related blog posts:

Lennon Wall, Prague

Long-term Effects on Bone Health of PPIs in Infancy?

A recent study –summarized by Pediatric News (MDedge): Antacid use in infants linked to increased fracture risk.

In this large study (874,447 children), more than 90% of the cohort had not received a prescription for any antacid.

An excerpt:

The large study revealed that use of proton pump inhibitors (PPIs) before age 1 year was linked to a 22% increased risk of fracture, compared with those not prescribed antacids…

The retrospective study’s cohort comprised 874,447 children born between 2001 and 2013 who had been in the U.S. Military Health System for at least 2 years…

Adjustment for preterm birth, low birth weight, sex, and a previous fracture barely reduced those risks: 22% increased risk for PPI use, 4% increased risk for H2 blocker use, and 31% increased risk for using both. The vast majority of children who took antacids had been prescribed them in their first 6 months, so the researchers calculated adjusted risk by age of exposure. 

My take: There are a lot of reasons to resist using PPIs in most infants, particularly lack of efficacy.  Potential harms of these medications, particularly at the youngest ages, should not be overlooked either.

Related blog posts:

Prague Castle and Charles Bridge

How often are acid blockers used in neonates?

A recent study (JL Slaughter et al. J Pediatric 2016l 174: 63-70) shows a high rate of acid blockers in neonatal intensive care units.  This study retrospectively analyzed the Pediatric Health Information System database (PHIS) from 2006-2013.

  • Of 122,0002 infants: 23.8% received either a histamine-2-receptor antagonist (H2RA) or proton pump inhibitor (PPI).
  • 19.0% had received an H2RA
  • 10.5% had received a PPI

My take (borrowed from authors): “despite limited evidence and  increasing safety concerns, H2RAs/PPIs are frequently prescribed to extremely preterm neonates…Our findings support the need for innovative studies.”  Wouldn’t it be nice if there was proof of efficacy in this population?

Vickery Creek, Roswell

Vickery Creek, Roswell