Deconstructing PPI-Associated Risks with Nearly 8 Billion Data Points and More on COVID-19 GI Symptoms (Video)

Link: 22 minute video —COVID-19 and the GI Tract -What We Know Right Now

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A recent study (C Ma et al. Gastroenterol 2020; 158: 780-82) used cross-sectional data from the National Ambulatory Medical Care Survey (NAMCS) (2006-2015) with a total 7,872,115,883 weighted observations.  They used this data to evaluate medication exposures and outcomes.

Key findings:

  • There was no association between PPI use and dementia, pneumonia, or intestinal infections.  There was a trend towards intestinal infections (AOR 1.48, CI 0.80-2.71) but this did not reach statistical significance. “Sensitivity analysis showed an association between PPI use and C difficile.”
  • There was an association with chronic kidney disease (CKD) (AOR 1.26); however, this was seen with a multitude of drug classes including statins, calcium channel blockers, and beta-blockers.

Discussion:

  • This study notes that a recent large randomized controlled trial found no statistically significant differences between those receiving PPIs and those receiving placebo except for intestinal infections.
  • With regard to CKD, “it is extremely unlikely that all of these medications increase the risk of CKD, and therefore, it is likely that these findings are due to residual confounding.”

My take: With the exception of C difficile/intestinal infections, this study provides further evidence of the safety of PPIs and a lack of association between these medications and purported PPI-related adverse events.  That said, it is still a good idea to limit use for appropriate indications.

Related blog posts:


Also, IOIBD recommendations for IBD patients and COVID-19 have been published.

Here is link as well:

IOIBD (International Organization for the Study of Inflammatory Bowel Disease) Recommendations (#76) for IBD Patients with Regard to COVID-19:

Full link: IOIBD Update on COVID19 for Patients with Crohn’s Disease and Ulcerative Colitis (3/26/20)

 

PPI and Poor Outcomes

A large observation study provides some bad publicity for proton pump inhibitors (PPI):

BMJ Open Access: Risk of death among users of Proton Pump Inhibitors: a longitudinal
observational cohort study of United States veterans (Y Xie et al BMJ Open
2017;7:e015735. doi:10.1136/bmjopen-2016-01573) Thanks to Ben Enav for this reference.

This study selected ~350,000 patients from a database which identified more than 1.7 million PPI users. These patients were ‘new’ PPI users.

Key finding:  Over a median follow-up of 5.71 years, PPI use was associated with increased risk of death compared with H2 blockers use (HR 1.25, CI 1.23 to 1.28).

The authors note the limitations of this observational study; however, they suggest that the findings cannot be fully explained by residual confounders.  They recommend limiting PPI use to “instances and durations where it is medically indicated.”

My take: As noted in a recent post (see below), some risks attributed to PPIs in observational studies do not pan out.  Yet, PPI therapies need to be better-targeted to those who will truly benefit from them.

Related blog posts:

The Battery, Charleston, SC

 

Regurgitation harder to treat than heartburn, especially for NERDs

While all pediatric gastroenterologists know that the title of this blog entry is right, it is helpful to have data.

A recent study (Clin Gastroenterol Hepatol 2012; 10: 612-19) used a reflux questionnaire to evaluate responsiveness of regurgitation from 2 randomized controlled trials.  The trials compared a newer acid blocker (AZD0865 dosed at 25-75 mg/day)) to esomeprazole (20-40 mg/day).  Patients had either non-erosive reflux disease (NERD , n=1460),  or reflux esophagitis, (RE, n=1314).  Inclusion criteria included the presence of substernal burning for ≥4 days/week.

Regurgitation-taste (RT), defined as an “acid taste in the mouth,” or regurgitation-movement (RM), defined as an “unpleasant movement of material upwards from the stomach” were analyzed.  Among NERD patients, either or both symptoms were present in 53% at baseline compared with 54% among the RE group.  In both NERD and RE patients, the presence of these regurgitation symptoms was associated with a poorer response to therapy.

  • Complete response of NERD patients with regurgitation symptoms:  RT 34%, RM 26%; in comparison to heartburn response of NERD patients which was 49%
  • Complete response of RE patients with regurgitation symptoms:  RT 44%, RM 33%; in comparison to heartburn response of NERD patients which was 55%

Additional references/blog entries: