PPIs and Associated Heart Risk

A NY Times review PPIs and Heart Attacks of PLos One study showing an association between PPI usage (eg. prilosec, prevacid, and nexium) and heart attacks -this study does not prove any causality, but is likely to spark some questions. Excerpt:

The widely used drugs known as proton pump inhibitors, or P.P.I.’s — gastric reflux preventives like Prilosec and Prevacid — may increase the risk for heart attack, according to analysis of data involving almost three million people.

A significant limitation of the study, in PLOS One, is that P.P.I. usage may be a marker of a sicker patient population, more subject to heart disease in any case.

Here’s NPR’s take on the same study: Data Dive -Possible Link Between PPIs and Heart Attacks

“The increase in risk is about 16 to 20 percent, depending on the particular drug involved”…

Someone with a low risk of heart attack doesn’t have much to worry about. “If your risk of a cardiovascular event or a heart attack is one in a million, now it is 1.2 in a million,” [Nigham] Shah [one of the authors] says.

“The problem is, it’s very easy to do studies of this sort that lead to conclusions that can be misleading,” says Dr. David Juurlink, a drug-safety researcher at the University of Toronto…

“Having a bad diet, drinking too much alcohol, smoking and all sorts of other things … might lead people to be on a PPI,” Juurlink says. One would expect those people to be at higher risk of heart attack, which leads Juurlink to think the medicine is likely not to blame.”

 

Also noted:

We still see this

Despite a number of previous studies regarding transient benign hyperphospatasemia which date back to 1954, pediatric gastroenterologists still see kids referred for this.  A new study analyzes 142 previous reports which included 813 cases (JPGN 2013; 57: 167-71).

Most of the alkaline phosphatase is produced in the liver and bone. “Sometimes a marked increase in alkaline phosphatase values is found in infants and toddlers without evidence of liver or bone disease…The temporary increase in alkaline phosphatase resolves without intervention within 16 weeks…is termed transient benign hyperphosphatasemia.”  With this disorder, the alkaline phosphatase is commonly ≥ 5 times the upper reference range.

Findings:

  • 733 cases were in patients <19 years of age; 80 cases were in those ≥ 19 years
  • Among infants and toddlers, the prevalence may be between 1.1% and 3.5%
  • The duration of elevation was ≤4 months in 80%
  • A preceding infection often preceded the reported cases
  • Our analysis “indicates that isoenzyme studies are not useful.” In about 50% the most prevalent isoform is from bone, though this may reflect poor clearance from the circulation.

Evaluation recommended by authors: aminotransferases, bilirubin, γ-glutamyl transferase, calcium, phosphorus, urea, and creatinine (eg. CMP, phosphorus, & GGT) –though they indicate that these may be waived by many experienced clinicians.

Bottom-line: Transient benign hyperphosphatasemia is likely the most common cause of elevated alkaline phosphatase in healthy infants and toddlers.  Sometimes this occurs in older children and adults. Recognition of this disorder may help avoid unnecessary investigation.