More Bad News for PPI's (and Indications for GI Prophylaxis)

Over the past year there has been significant negative press concerning PPI’s. This months Archives of Internal Medicine is nearly entirely dedicated to the problems with PPIs. This got my attention because PPI’s are often handed out like candy on our inpatient service. Why? Well, they are viewed as benign and they work. Anyone who suffers from GERD will attest to how great they are. They also give us something to give patients with atypical chest pain. Add in ‘GI prophylaxis’, and most of our patients end up on PPIs at some point. But who cares? 

Lets look into the problems associated with PPI’s. 

1. Interaction with clopidogrel and even ASA:
I go into detail on the clinical ramifications of the interaction with plavix in my last blog, but to summarize, it is not just a theoretical risk. There does appear to be an increase in AMI and re-admission with the combination. 
Now there is an additional study showing interaction with ASA (Heart 2010 mar 96:368). It will be interesting to see if this a clinically relevant interaction or not. 
Take Home: No ppi with plavix, especially post-stent.

2. Increased Risk of C. dif 
This has been reported in the literature for years, but not very well known in the community. It makes sense. One of our first lines of defense from fecal-oral spread of infections is our stomach acid. This true is for travelers diarrhea along with C. dif colitis. By taking a ppi, the acid is suppressed, and the inoculation load becomes significantly less.
In this months Archives of Internal Med, there is another article highlighting the increased risk of recurrence of C. dif with PPIs. Past studies have shown a 2-3 times higher incidence of C. dif in patients on a PPI, and this study showed a 42% higher risk of recurrence of C. dif (Arch Intern Med. 2010;170(9):772-778). Patients on a ppi had a recurrence of c. dif 25% of the time vs 18%. This is likely even more true for our elderly patients.

3. Increased risk for Hospital Acquired Pneumonia
Again, not too surprising. Nearly all patients aspirate while acutely ill. If the patient is on acid suppression, then it is more likely that the aspiration will lead to an infection (JAMA. 2009;301(20):2120- 2128).

4. Fractures
There have been long term studies which have shown increased risk of hip fractures and other osteoporetic fractures in patients taking a PPI (JAMA. 2006;296:2947-2953). It is thought that the acid suppression leads to decreased Ca absorption. There has also been some comments on Vitamin D deficiency with PPIs (sorry do not have a source for this one, it is based upon memory). 
This was looked at again this month in Archives. The study did show an increase incidence of fractures with PPIs, although not in hip fractures which was what the JAMA article noted (Arch Intern Med. 2010;170(9):765-771).

A final article in the journal highlighted to overuse of PPIs. The editorial comments that PPIs are the third highest prescribed drug class, but have been found to be inappropriately prescribed in 53-69% of the time! This is an enormous number when you consider PPIs is a $13.9 billion dollars a year industry. That is a lot of money that is spent on a medication not indicated. How are these prescribed inappropriately? See if you have been guilty of any of these, I know I have:
1. Started in the hospital for “prophylaxis” and continued at d/c. The PCP notes that the patient is now on a PPI and continues it since we started it. Years later the patient is still on a PPI for no clear reason.
2. The ICU starts a PPI for prophylaxis, which is often appropriate, and we continue it on the floor and at d/c.
3. The patient has a true indication for a PPI, but instead of treating for the appropriate time frame, they stay on the PPI for life. 
4. The patient has dyspepsia and instead of doing a step up approach, we go to a PPI. Once on, they do not get off despite the etiology for the dyspepsia likely healed by the PPI.
Add in the cost related to the adverse effects, and the societal cost for PPIs is quite significant.

On the inpatient service, I will have a renewed effort at stopping this pattern. I’ve contributed greatly to the overuse prescribing of PPIs, but no longer. Patients who come in on a PPI will have their PPI stopped if they do not have an indication. Patients who do not meet criteria for GI prophylaxis will not receive any, and those who do will be given a H2 blocker unless contraindicated. The PPI or H2 blocker will be stopped when clinically indicated and not be continued at the time of d/c. This is my mission for the up coming year. Lets see how I do.

Indications for GI Prophylaxis

(The American Society of Health System Pharmacist Practice Guideline)

ICU Patients with:
Coagulopathy (plt <50,000; INR >1.5, PTT 2 times upper limits of normal)
Ventilation of over 48 hours
GI ulceration or bleeding in the past year

or

Two or more of the following risk factors:
Sepsis
ICU stay over 1 week
Occult bleed lasting over 5 days
Steroids