Evidence of PPI danger grows

Matt Woodley

5/06/2019 3:32:34 PM

Extended use of common heartburn medication has been linked to potentially fatal cardiovascular disease, stomach cancer and chronic kidney disease.

Experiencing heartburn
The latest research indicates the risk of fatality increases with the duration of PPI use, even at low doses.

Proton pump inhibitors (PPIs) have been associated with an increased risk of premature death since 2015. New research has now found correlations between their use and negative health outcomes.
According to the Pharmaceutical Benefits Advisory Committee (PBAC), high-dose PPIs appear to be overprescribed in Australia, for excessively long periods of time and particularly among older people.
Across 2013–16, 95% of prescriptions were considered ‘high’ or ‘highest’ dose, leading the PBAC’s Drug Utilisation Sub Committee (DUSC) to recommend changes to the restriction levels and number of repeats.
The recommendation resulted in restrictions being placed on the prescription of PPIs listed on the Pharmaceutical Benefits Scheme (PBS) General Schedule in May, as well as changes to the terminology, criteria and the number of repeats.
However, the latest research indicates the risk of fatality increases with the duration of PPI use, even when the drugs are taken at low doses, as more than 80% of analysed PPI users were on low doses of the prescription drug, or those equivalent to doses offered in over-the-counter versions.
‘This suggests the risk may not be limited to prescription PPIs, but it also may occur at over-the-counter doses,’ lead author Assistant Professor Ziyad Al-Aly said.
‘Taking PPIs over many months or years is not safe, and now we have a clearer picture of the health conditions associated with long-term PPI use.’
The Washington University School of Medicine study utilised 157,625 medical records, sourced through the US Department of Veterans Affairs, of people who had been recently prescribed PPIs, and 56,842 people who had been newly prescribed H2 blockers.
They followed the patients – 214,467 in total – for up to 10 years and discovered a 17% associated increased risk of death in the PPI group compared with the H2 blocker group. Death rates for PPIs were 387 per 1000 people, compared with 342 per 1000 for H2 blockers.
Specifically, 15 per 1000 PPI users died from heart disease; four per 1000 from chronic kidney disease, and two per 1000 from stomach cancer.
Death rates due to cardiovascular disease were 88 among the PPI group and 73 among the H2 blockers group, while death rates for stomach cancer were six in the PPI group and four in the H2 blockers group.
Death rates due to chronic kidney disease were eight and four in the PPI and H2 blocker groups, respectively.

The researchers therefore concluded, ‘taking PPIs is associated with a small excess of cause specific mortality including death due to cardiovascular disease, chronic kidney disease, and upper gastrointestinal cancer.’
Additionally, the study found that more than half of the people taking PPIs did so without a medical need, and that this group had the highest mortality rate.
‘Most alarming to me is that serious harm may be experienced by people who are on PPIs but may not need them,’ Assistant Professor Al-Aly said.
‘Overuse is not devoid of harm.’

Note: This article has been amended to show an association rather than causative effect between PPIs and negative health outcomes.

heartburn PPIs proton pump inhibitors

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Dr George Nicholas Kostalas   6/06/2019 4:12:23 PM

Can I suggest that it is better if journalists and researchers express their results in the format of Numbers needed to treat (NNT) or Numbers needed to harm (NNH). This is a much better way for GPs to understand the significance of the results.

Dr Muhammad Iqram Pervez   7/06/2019 2:18:29 AM

This is real challenge to cease PPIs due to misconceptions among the users, like opioids. I think community awareness is more important than doctors awareness!! Any helpful suggestions to counsel people without confronting??

Siva Muppala   8/06/2019 9:56:28 AM

No medication is free of risks. Is it acceptable to prescribe PPIs liberally with out clear indication and now try to reduce their use ? If we prescribe genuinely how we reduce their use? What should have happened with out PPIs in terms of gastric ulcers and gastric bleeding? It is concerning every time I see a client, who tells me he is not sure why he is taking medication but tells me the doctor ask him to take.

Catherine regan   11/06/2019 11:14:03 AM

And the comparative risks for someone with symptomatic reflux and severe ulcerative oesophagitis (no Barrett’s) stopping the PPI?

L. Morris   11/06/2019 12:01:51 PM

Are those death rate stats right?
And, as with any epidemiology study, does correlation = causation.

Antoine D'Arche   11/06/2019 12:02:02 PM

Retrospective analysis. Correlation does not equal causation. Risk of not using PPIs vs risk of using PPIs. Drs did not make PPIs available OTC. Should I go on?

Melbourne based GP   11/06/2019 3:59:55 PM

I have read this study which was published in the BMJ on the 30 May 2019 and discussed the findings and conclusions with a number of my gastroenterology colleagues. They study did not correct for confounders well so this makes interpreting the data difficult. Heightened vigilance with any pharmacotherapy we prescribe as GPs is always warranted.

A Jackson   11/06/2019 6:14:27 PM

This article has conveniently appeared just as the federal government uses the PBS system as a blunt weapon to have doctors submit to their wishes on PPIs. It is wholly biased, for example there is no detailed analysis of the the number of people whose deaths have been prevented since PPIs were introduced, not to mention morbidity curtailed, and the substantial relief of GORD symptoms provided by this highly effective medication. The latter group would be often using PPIs on a prn basis when esomeprazole 40mg provides better immediate relief than the 'stepdown' 20mg strength.
And this in the week that the Tasmanian Coroner has criticised doctors in Tasmania's north for the "preventable death" of Margaret Patricia Kenney due to the unwarranted cessation of her PPI namely pantoprazole - perhaps those doctors had 'taken notice' of the current government push in relation to PPI prescribing and acted accordingly.

Melbourne GP   11/06/2019 10:54:34 PM This prospective study begs to differ saying no increased cardiovascular or renal risk

Zac Alibrahim   15/06/2019 2:24:47 PM

The cohort researched here are elderly people with multiple comorbidities and taking a plethora of pills, how do we filter PPI from all other factors? I believe this need validation with prospective control trials

Panagiota Milonas   16/06/2019 3:32:16 PM

I wonder are people are taking PPI's for undiagnosed angina or inferior ischaemia symptoms. Are patients with known cardiovascular disease - on anticoagulants / anti-platelet therapy +/- aspirin and have oesophagitis made worse by the same? This in my view result in even more use of PIP's. And then as noted above there is a plethora of medications also taken for osteoarthritis, hyperlipidaemia, hypertension, diabetes (comorbiditis) that contribute to increased PIP use which may also contribute to risk of Cardiovascular disease. cancer and /or premature death of some cause.
I wonder are patient with stomach cancer initially self treating with otc PIP's - how many are chronic persistent carriers of H. Pylori and how many are briefly treated with PIP's just prior to diagnosis.
Unless this data is corrected for the above factors it can not be considered cause and effect but rather is the realisation that death from all causes commonly affects the over 50's.