PPI(Proton Pump Inhibitors) Use and Atherosclerotic Cardiovascular Disease

I have written past blogs regarding the potential adverse impact of the use of proton pump inhibitors, the drugs commonly used for reflux.  These problems evolve slowly over time with ongoing use which obscured them during the clinical trials that led to the approval of these drugs as they tended to be shorter term studies.

One of the concerns that previously emerged with ongoing use of PPIs was that of atherosclerotic cardiovascular disease events (ASCVD ) such as myocardial infarction, stroke and peripheral vascular disease.  A new study has again confirmed that risk.  The study followed over 300,000 adults without known vascular disease for 12 years comparing the rates of new diagnosis of these diseases in those regularly using PPIs and those who did not.

The regular use of these drugs increased the 12-year risk of new vascular disease by 16%.  Looking at the typically used drugs, they created different risk levels although they all were associated with increased risk.  The lowest risk was found with lansoprazole (Prevacid) at +11% and the highest with pantoprazole (Protonix) at +40%. 

An interesting observation was that the risk was greater in those subjects who were given these medications without strong clinical indication for their use which unfortunately is common both by prescription without good indication or by over the counter use.  It is estimated that there are 113 million PPI users annually and that as much as 70% of users are doing so without appropriate indication.

Many of the symptoms such as indigestion, reflux and epigastric pain are the result of otherwise manageable problems including food sensitivities, poor motility in the digestive tract and microbiome imbalance called dysbiosis.  These disorders should be investigated and appropriate solutions used resolving symptoms without PPI use.

The researchers of this latest study summarize, “PPIs were associated with increased risk of ASCVD, particularly amongst participants without indications for medication. Our findings are of important practical significance and suggest that clinicians should be cautious in prophylactic use of PPIs.”

Every function we are endowed with serves a purpose, one that we can rarely do without.  I had an interesting patient encounter about 35 years ago that vividly keeps that point in my mind.  The wife of a good general surgeon came in to see me with chronic pain in her small toe.  I asked her if any other providers had looked at the problem.  Her response was that her husband had and suggested that he could just amputate that toe as it did not do much anyway.  Obviously she felt otherwise.

Initiating digestion with stomach acid serves important purposes such as beginning the proper breakdown of food molecules, cleansing the less preferred bacteria in the digestive tract and facilitating the absorption of nutrients such as B12, calcium, magnesium and others.  Stopping those functions without trying other, safer solutions is not the best approach.


Ament et al.  REDUCING ADVERSE EFFECTS OF PROTON PUMP INHIBITORS. Am Fam Physician. 2012;86(1):66-70.