OT: PPI's and the cancer risk ITRW?

[T i m]

Hi all,

Not sure where else to run this past anyone and I know there are people here who understand this field better than I.

Like many people in the Uk, a while back I was put on a daily 'Proton Pump Inhibitor' (30mg / day)

I was prescribed it because of a duodenal ulcer (and a follow up endecoscopy suggested it was 'getting better').

But a while back something appeared on the news linking the use of such PPI's to an increased risk of gastric cancer (I believe from a survey done in Hong Kong).

The following seems to cover many of my questions and possibly some of the answers (not that I read or understood it all).

This goes into more science:

And this further still (and over my head):

Further, we took Mum (87) to the hospital yesterday as she had been suffering with heartburn for a while now and after a quick bronchoscopy they put her on Omeprazole (20mg), another name I've seen mentioned and linked to 'increased risks'. She's not taken any yet as I said I'd look into it for 'us' (and she's had the heartburn for quite a while etc). I'm particular concerned because I thought I read that the actions of some of these drugs isn't reversible? ;-(

Now I guess my question is: Could it be that the negative consequences of (say me) not taking said PPI actually be greater than me taking it?

eg. If it increases the risk of a gastric cancer from 400 to 401:1 when the general background risk is 1:3 anyway, is / could the increased risk be justified for the typical net gain?

What are the alternatives as I think I understand there were 'other' medicines that were used to resolve / alleviate such gastric issues that didn't appear to have the same risks (H2 blockers)?

Thoughts please (questions welcomed). ;-)

Cheers, T i m

[Fredxxx]

The name prompted me to look up the range of drugs. The name sounds best placed in a Sci-Fi movie.

I presume you have already found this:

Its unusual to see a drug target a cell in such an efficient way: "PPIs have a half-life in human blood plasma of only 60?90 minutes, but because they covalently bind to the pump, the half-life of their inhibition of gastric acid secretion lasts an estimated 24 hours".

It seems that any range of problems are not strongly correlated with the drug. It does recommend the lowest dose to achieve the desired therapeutic result.

Personally I would be looking at two things, quality of life and consequence of taking the drug. It looks like a no-brainer to me.

[T i m]

;-)

I did, but not sure it has been updated to include / consider the recent studies?

Quite, as would be desired re most drug use presumably?

Correct, that was my question.

So, what odds are you working on?

Cheers, T i m

p.s. A while after being put on the PPI I had other symptoms (possible side effect) so was put on a double dose 'temporarily', until I too had a bronchoscopy ... but as it's not going to be for a while and reading how much taking that sort of dose increased the risk, I've taken myself off it all (for now anyway).

[T i m]

Me neither.

So I understand.

It's under a similar logic I stopped taking my statins ... as I'm not convinced they fully understand what cholesterol is all about (and the causes of high levels etc).

(Along these sorta lines)

Cheers, T i m

[Martin Brown]

[snip]

Sounds like they are trying to give the healing process the best chance of succeeding. Short term use to lower acid levels in the stomach.

It sounds like asking your consultant about the possibility of the alternative H2 blocker treatment might be worthwhile. But a serious stomach bleed could be dangerous in its own right in the elderly so I don't think it is a good idea to ignore the medication provided.

The PPI risk is 2-4x larger but it is still only one in 400 and that means that 399 of the 400 benefit from treatment - not bad odds at all.

The one thing that stands out to me is that having excess acid and acid reflux burns will potentially predispose you to cancer anyway so the cure may still be a better bet than suffering and leaving it untreated.

What they seem to have shown is that knocking down H. Pylori and using a acid blocker was the key. The people who seem to be most at risk of cancer are those who have persistent gastritis after that treatment.

Long term PPI use I think is probably a bad idea.

[T i m]

I asked if that was the plan when initially prescribed Lansoprazole and was told I would probably have to take it indefinitely. ;-(

Yes, that was my thought Martin.

I know ... it's just I try to avoid taking anything if possible (inc antibiotics) and especially would like to avoid the std cocktail of pills many elderly seem to take these days. ;-(

Are they the figures you have gleaned yourself Martin or from me? If yours / independent then I agree, 400:1 *could* be considered reasonable odds, given today's 1:3 (is it?) for cancers in general? ;-(

Me too.

So, do you think we are just talking 'luck' here where someone carries H. Pylori but with no issues whereas with others that results in an ulcer? Or are there some strong / known lifestyle choices that make someone more predisposed to the H. Pylori causing issues and if so, do we know what they are?

I mean, are H. Pylori ulcers more or less of an issue where people regularly eat 'spicy' or other foods etc?

The doctor recommended I try to keep away from alcohol and very spicy foods for the acid reflux (the foods for the stomach acids and the alcohol because it relaxes the sphincter muscles etc) but I wasn't a regular (hot) curry eater or alcohol consumer?

Cheers, T i m

[Peter Parry]

The best source of unbiased evidence based medical advice is the Cochrane collaboration,

a British non-profit, non-governmental organization formed to organize medical research findings so as to facilitate evidence-based choices about health interventions. They do this primarily by producing Cochrane reviews.

One great advantage of the Cochrane reviews is that they all include a plain language summary of the results..

One you might find interesting is :-

is the full review.

[Peter Parry]

From the Cochrane review linked in my earlier post :-

"We concluded that there was no clear evidence to support the notion that the long-term use of PPIs could promote the development of pre-cancerous lesions. However, there was a potentially elevated risk of developing a thickening of the stomach lining (hyperplasia) among participants with long-term PPI use, which is considered as a possible pre-condition of gastric carcinoid (a relatively benign (non-cancerous) tumour that develops within the stomach lining).

Quality of the evidence

Currently, available evidence was of low or very low quality, due to their study design and the large proportion of missing data. We therefore suggest future well-designed clinical trials should be performed for providing better understandings regarding this question."

[T i m]

Thanks for that Peter ... just thinking out loud ...

So (from your last link) it's the:

"PPIs are the most effective drugs used to reduce gastric acid secretion (called antacids) and they are commonly prescribed worldwide. Although generally safe, their effectiveness and safety for long-term use remains unclear. It has been suggested that the long-term use of PPIs could promote the development of pre-cancerous lesions in the stomach, which might subsequently increase the occurrence of stomach cancer. Therefore, the safety issues of long-term PPI treatment needs to be addressed."

... bit that has me concerned.

The Cochrane review seems to be over a similar time period as the case study done in Hong Kong with the UCL although the conclusions of that were still being noted in 2015, rather than 2014.

Cochrane only seems to cover 1789 people versus 63,397 from the HK/UCI one (if I understand it correctly).

I am particularly interested in bits like:

"Taking PPIs was associated with a more than doubling (2.44) in the risk of developing stomach cancer, while taking H2 blockers was not associated with a heightened risk."

eg, If there is an alternative medication that has the same effect but without the (or those) risks, why wouldn't I take those instead?

Cheers, T i m

[T i m]

Oh dear.

I'm pretty sensitive that way are even asked for a double dose of the anaesthetic spray but not sure if it made any difference (other than psychologically). It was hard that's for sure but I managed to keep it all together. ;-)

Oh dear.

So it seems. ;-(

The bottom line was I was trying to find some sort of real world feedback to 1) just how increased the risks were over the current background levels and 2) if there were any alternative medicines that offered lower risks?

It seems there could be an answer to the latter, eg, using a 'H2-receptor antagonist' over a 'proton pump inhibitor'?

Cheers, T i m

[Peter Parry]

"The adjusted absolute risk difference for PPIs versus non-PPIs use was 4.29 excess GC (95%?CI 1.25 to 9.54) per 10,000 person-years." (from the Hong Kong study)

[T i m]

Thanks for that Peter ... I seem to have a low data overload threshold with such things outside my typical area (like programming etc). ;-)

So, can we conclude that although there *is* an increased risk of cancer with the (especially long term use of PPI's), the risk could be considered in amongst the background noise?

Cheers, T i m

[Peter Parry]

It would seem so. This often proves to be the case when you have contradictory good quality studies looking for tiny changes. The other guarantee of any study proving to be inconclusive is if it appears in the Daily Mail or Express as an "amazing find", "Study proves" or "stunning breakthrough".

[Vir Campestris]

Have you asked your doctor? He may not be a specialist, but as you say these things are common and she may know.

Andy

[T i m]

Sorry for the delay Andy etc.

No, I haven't (yet), it just seems like it's one of those things they are handing out like blood pressure and cholesterol tablets these days?

I'm still awaiting the results from all the tests and if I get called in for a review, I'll ask then.

Cheers, T i m