PPI Use and Death Risk

In recent weeks we have seen articles linking the long term use of proton pump inhibitors such as Nexium (esomeprazole), Protonix ( Pantoprazole), Aciphex (Rabeprazole), Prilosec ( Omeprazole) with an increased risk of community acquired pneumonia, kidney disease, bone disease, cognitive dysfunction and increased risk of clostridia difficile infection (antibiotic related colitis). These drugs are commonly used short-term for the treatment of ulcers, gastro esophageal reflux disease, Barrett’s Esophagus, upper GI bleeding and H Pylori infections.

Often, after the prescribed treatment period, physicians try to discontinue the use of PPI’s but the patients have a return of their symptoms. With these medications now being sold over the counter, it is very difficult to get a symptomatic individual to curtail therapy even if the long-term risk is daunting.

I often attempt to switch patients to “old fashioned” antacids such as Tums, Rolaids, Mylanta, Gaviscon or even the H2 receptor blockers such as Tagamet and Zantac (Cimetidine and Ranitidine). All too frequently the response is that “my symptoms returned and only get better with the PPI.”

A study published in the British Medical Journal looked at data from the Veterans Administration data base for a period of two years, and selected a representative group of PPI users and non-users. They then followed them for 7-8 years.

Patients taking PPI drugs regularly had a 25% increased risk of death. There was no apparent reason why these medications led to a higher death risk. Further studies will be needed. The conclusion is take them for as short a period of time as possible.

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Increased Dementia Risk in Senior Citizens Due to Proton Pump Inhibitors (PPIs)

Brittany Haenisch, PhD of the German Center for Neurodegenerative Diseases in Bonn, has reported in JAMA Neurology, a study from health insurance data suggesting that taking Proton Pump Inhibitors (PPIs) such as Aciphex (omeprazole), Protonix (pantoprazole), Nexium (esomeprazole), and Prevacid (lansoprazole), was associated with a markedly increased risk of developing dementia. The correlation was stronger in men than women with a slightly increased risk for those taking Nexium.

The study, conducted from 2004 through 2011, looked at 73,679 people age 75 years or older and who were free of dementia at “baseline”.  It revealed 29,510 patients (40%) developed dementia and, of these, almost 3,000 (average age of 84) were taking a PPI medication. The authors concluded that avoiding PPIs may prevent dementia.

All of these medicines are now freely sold over the counter not requiring a prescription. Their use has dramatically increased. There is belief from animal studies that PPIs cross the blood brain barrier and effect the production of amyloid and tau protein associated with dementia. In humans, B12 levels can be lowered effecting cognitive ability. None of this data shows a clear cause and effect relationship so we cannot say PPIs hasten the onset or cause dementia. Newer well designed controlled and blinded studies will be needed for this purpose.

In the interim, I will ask my patients to reduce or avoid these medications. We can treat heartburn and indigestion with products such as antacids, weight loss, eating smaller portions and staying upright after those meals, loosening your belt at the waist and avoiding those foods that reduce lower esophageal sphincter muscle pressure leading to reflux.

There will be some with conditions such as Barret’s Esophagus, which is precancerous, and recent bleeding ulcers which require the use of PPIs for eight or more weeks and then switch to Tums, Rolaids, Gaviscon or Carafate. Some patients will need the PPIs for symptom relief beyond eight weeks and they will need to make a tough decision between symptom relief and increased dementia risk while the researchers search for the answer.