Acid Blockers Increase Mortality Risk

5. September 2017

Due to the use of PPI, operations to treat peptic ulceration have become a rarity. Nevertheless caution is advised, because there are more and more often problems associated with acid blockers. One study establishes a link to the chance of dying – OTCs come into play here.

Proton pump inhibitors such as pantoprazole and omeprazole are in absolute terms among the most frequently prescribed drugs. Gastric resections like Bilroth I or Bilroth II have indeed become a rarity in cases of peptic ulcers due to pharmacotherapies. Alongside this we see ever more often undesirable effects.

Indications of higher mortality rates


Ziyad Al-Aly © Washington University School of Medicine

Ziyad Al-Aly from the Washington University School of Medicine In St Louis wanted to know the consequences of using PPI in long-term therapy. The basis of his work was a cohort including nearly six million US veterans. The researcher chose a comparatively new approach by comparing different drug classes. Doctors prescribed PPI to 275,000 patients, and nearly 75,000 patients received H2 blockers. All persons were closely scrutinised for 5.6 years.

In his initial evaluation, Al-Aly found that the mortality rate in his PPI group rose significantly by 25 percent. However his study design strategy came somewhat undone: patients with more severe underlying diseases were more frequently prescribed proton pump inhibitors by physicians. Therefore, together with colleagues, he tried to mathematically correct this statistic distortion.

Depending on the procedure considered, the risk of mortality with PPIs was still 16% or 21% higher than with H2 blockers. Here also, the differences between the two groups were significant. In other words, purely on the basis of numbers Al-Aly concluded that there was one additional death per 500 patients who take PPIs over twelve months.

Indicators – no evidence

The association uncovered by Al-Aly ultimately demonstrates no causality, but it does fit in seamlessly with other publications on the risks of PPI. Michael Howell from the Harvard Medical School in Boston as part of an observation study evaluated the release diagnoses of 101,796 patients following inpatient hospital stays. For these patients the risk of infection from nosocomial Clostridium difficile was associated with the gastric acid blockage. Where physicians prescribed H2 receptor antagonists, this figure was 53 percent, with daily PPI administration 74 percent and even more frequent use even 136 percent. Similar effects occurred with patients who were treated using PPI in order to reduce the risk of possible bleeding.

Clostridium difficile has also been the subject of work done by Amy Linsky from the Boston Medical Center. In doing a retrospective study she analysed data from 1,200 patients with infections of diverse origins. Doctors had at first successfully treated all the people with metronidazole or with vancomycin. With 25.2 percent (PPI) versus 18.5 percent there was recurrence of the infection.

In another publication, Shelly L. Gray, University of Washington, together with her colleagues pursued the question of whether statistical associations exist with fractures. The researcher used the records of 161,806 participants aged between 50 and 79 from the Women’s Health Initiative. During the eight-year follow-up period, 21,247 new fractures occurred. If women had been taking PPI, the risk of spinal fractures was increased by 47 percent. In the case of forearm and wrist fractures Gray calculated an increase of 25 percent. Changes in the absorption of individual nutrients such as calcium or D-vitamins are discussed as an explanation.

Yet it doesn’t end there: further publications suspect connections between PPI and acute interstitial nephritis, myocardial infarction, cases of dementia and pneumonia. In all cases, scientists indeed do find associations but no causality. Until there are more methodologically high-quality studies, doctors are only left with the option of prescribing more moderately.

Stop indiscriminate use


Matthias Ebert © University Medical Centre Mannheim

“These medicines are effective and important in the treatment and prevention of certain acid-associated diseases of the stomach such as reflux disease, gastro-duodenal peptic ulcer disease, Barrett’s esophagus and Zollinger-Ellison syndrome”, says Professor Dr. Matthias Ebert, Director of the II. Medical Clinic of the University of Mannheim (Germany). In some cases the use of these medications is appropriate as gastric protection.

More and more frequently PPIs are being used against ailments where their use cannot be scientifically proven, such as irritable stomach syndrome, he says. Indiscriminate use is also favoured by the fact that the medications are also dispensed over-the-counter at pharmacies, Ebert asserts.

When patients abruptly cease taking the medication and there is no medical supervision rebound effects sometimes occur. “This often leads to patients continuing to take the drug and remain with it in the long term”, Ebert adds. It is advised that proton pump inhibitors not be used in the long term without a definite doctor’s diagnosis.

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