10 ms·

Popular stomach acid blockers linked to higher death rates

56 points by rezaprima 9y ago

nerdponx 9y ago
What did (or didn't) this study control for? I appreciate them stopping short of saying that proton pump inhibitors kill people, but without a causal mechanism it seems more plausible that chronic use is correlated with other life-shortening factors.
- andy_ppp 9y ago
  There’s an obvious issue that you stomach acid is there to digest food correctly and also provide the environment for growing the correct microbiome; both of which are pretty vital functions I’d say.
- TillE 9y ago
  They didn't find a similar effect with H2 blockers, which pretty strongly suggests a specific problem caused by the mechanism of PPIs.
  - tpeo 9y ago
    Only if the choice between PPI and H2 blockers is random. If there's some self-selection going on, there isn't much to say about PPI's impact on patient health given what we know about H2.
- somethingawful 9y ago
  Yeah, lots of risk for confounders and selection bias in a study like this. If you take the huge number of patients with a history of GI bleeding (for which PPI therapy is well-proven), those are patients who already have an elevated all-cause mortality risk. They also selected patients who had at least one creatinine measure in their EHR; so probably people who are more likely to have background renal disease. And using US veterans makes it hard to generalize to the greater population. However, they also saw elevated risk in patients who didn't have a de-facto indication for PPIs (GERD, GI bleeding, etc), so maybe there is something to this. Honestly, it's kind of an amateur study design. I think the conclusion to draw here is we need a large randomized control study to look at this issue. Regardless, as a physician, I agree with the study authors that if a patient doesn't have a specific indication for PPI, they shouldn't be on one. Then again, I don't need a study to tell me that; it's my feeling about ALL medications.
- ozi 9y ago
  This study is bogus because they didn't analyze cause of death or account for the reason for using PPI. H2 blockers and PPIs are often not prescribed for the same things. For many serious diseases PPIs are commonly prescribed as a secondary medication (eg with Plavix) where H2 blockers would make no sense. That's why the group sizes differ greatly.
danjoc 9y ago
... in a small, biased sample.
- tpeo 9y ago
  Biased, maybe. But the sample sizes are pretty big, whether "bigness" refers either to absolute numbers or to being big enough such that whatever they're estimating will come pretty close to the true value of that variable for similar populations. I mean, the smallest sample is 70k plus.
- charlesism 9y ago
  No, but as always they trot out the relative numbers. > "25% greater risk of death, compared with H2 blockers" Whether that means anything to me depends on what my odds of dying are on H2 blockers. If it's 1 in 3 then I care. If it's 1 in 3,000,000 then I don't.
greglindahl 9y ago
PPIs are pretty difficult to stop taking -- I started taking Prilosec in 2004 for reflux and after a few tries at stopping abruptly resulted in horrid symptoms, I finally manged to tail off by reducing the dose 1/8 at a time every 2 weeks, over a total period of 2 months. From all accounts H2 blockers are easier to quit. I was pleasantly surprised that I didn't have any heartburn or reflux issues when I was done -- apparently the original cause was gone.
- jgalt212 9y ago
  This has been my experience as well. I found it helpful to taper the Prilosec, and move over the seemingly less dangerous Pepcid. And then taper the Pepcid to 0.
- notadoc 9y ago
  Did you adjust your diet during that period of time? What do you think was the original cause?
tpeo 9y ago
What if PPI users are more likely to have some other health issues compared to other patients due to some unobserved variable (e.g. lifestyle, strength of the physiological reaction to stress, genetic factors affecting both the likelihood of becoming a PPI user as well as the likelihood of having other health issues)? Oh, man... correlational studies... shame they didn't directly link to the article, too.
Ocerge 9y ago
Getting off of PPIs is a miserable experience. It gave me the worst acid reflux of my life, lasting almost a whole month. Everything is back to normal now (I don't think I should have been taking them in the first place), but I wonder if the crappy withdrawal process contributes to this somehow.
- senectus1 9y ago
  I've been on them for about 10 years, for the last few years I've halved the dosage. I might have to talk to the bonesaw about halving it again with the intention of getting off them. my experience though is that if I stop taking them I get it pretty bad and my energy levels go right out the window. I just become sloth like all day every day and cant think worth a damn.
  - ppiuser 9y ago
    > I just become sloth like all day every day and cant think worth a damn. A heartburn session and brain fog seem to be linked imo.
ppiuser 9y ago
Not something I enjoy reading after being on lansoprazole for around 8 years for heartburn. I decided to get off them with dietary changes a couple years back after reading how they are approved for short term doses and long term effects were untested. Doctors never showed much interest in discovering and treating the cause of the acid problem and even found it odd that I was trying to get off the tablets. I haven't been able to find if the damage they potentially cause in areas beyond the stomach reverses over time.
- senectus1 9y ago
  so how are you controlling the burn now?
  - greglindahl 9y ago
    After you've been on a PPI for a long time, you probably don't have heartburn anymore for the original reason. After I tailed off I occasionally have a throat spasm, but no reflux. If I did have significant heartburn or reflux again I'll definitely use an H2 blocker, and only for a short period of time.
  - ppiuser 9y ago
    Through trial and error I came to a low-carb(/low GI?) paleo style diet which seems to be inline with what other suggest. Alcohol, sugar and even stress definitely make it worse for me at least. edit: Special occasions where I might indulge in the above triggers I'll end up using an antacid for a day or two.
ianai 9y ago
They're talking about millions of data points. They could probably find significant correlations between anything at that point.
- robert_foss 9y ago
  Instances sure, but statistically significant correlations most likely not.
senectus1 9y ago
It bugs me that they just say "risk of death" which could mean anything; being shot, dying in a car accident, getting cancer having a heart attack... which is ridiculous I mean they do mention food poisoning and dementia etc but nothing about which of these factor strongly against the numbers of those that died. Is the food poisoning numbers effected by the poor nutritional practices (obese buffet eating crowds?), I know that many PPI takers are on the drug due to poor eating habits, where others are on it despite excellent eating habits. Also, a common reason for dementia symptoms is B12 deficiency which is a known problem with PPI and common advice for those taking it is to bump their intake of Vit B12. so really.. this study is looking very loosey goosey to me.
arnoooooo 9y ago
Suffering from acid reflux, I read at some point (I guess it was on Mayo Clinic) that something like 80% of people diagnosed as producing too much acid actually produce too little. Since stomach valves are pH activated, having too little acid causes the valves not to clause, which can result in reflux or downstream acid leakage. I tested this by taking HCL supplements, which did fix the issue.
- dustinmr 9y ago
  Would love to read the study if you can find it.
- ipunchghosts 9y ago
  > read at some point (I guess it was on Mayo Clinic) I would strongly suggest checking your sources. Many internet "doctors" aka charlatans, state low acid is a problem. I asked my doctors at John Hopkins about this and they said it was bunk.
- raarts 9y ago
  I tried that too. But it made no difference whatsoever.
kazinator 9y ago
Is that a higher death rate compared to the entire population which includes people who have no need for these blockers? Or compared to just those who need the blockers just as much as the users, but don't use them?
aladoc99 9y ago
Looking at the article in BMJ Open, I don't see that they controlled for obesity, either by BMI or any other measure. This is a huge confounder, making reflux symptoms worse and being an independent predictor of mortality. If I'm right, this is a huge oversight on their part.
- jawilson2 9y ago
  "External adjustment to estimate the impact of three unmeasured confounders, including obesity, smoking and use of therapeutics including anticoagulants, antiplatelet agents and non-steroidal anti-inflammatory drugs, shows a net confounding bias of 9.66% (see online supplementary figure 5). The total bias could move a null association between PPI and death from HR 1.00 to HR 1.10 (reflecting the net positive bias of 9.66% rounded up to 10.0%). The association we observed between PPI and death was 1.25>1.10, which cannot be fully due to bias of unmeasured confounding." "Covariates included age, race, gender, eGFR, number of outpatient serum creatinine measurements, number of hospitalisations, diabetes mellitus, hypertension, cardiovascular disease, peripheral artery disease, cerebrovascular disease, chronic lung disease, cancer, hepatitis C, HIV, dementia and diseases associated with acid suppression therapy use such as gastro-oesophageal reflux disease (GERD), upper gastrointestinal (GI) tract bleeding, ulcer disease, Helicobacter pylori infection, Barrett’s oesophagus, achalasia, stricture and oesophageal adenocarcinoma.25–28 eGFR was calculated using the abbreviated four-variable CKD epidemiology collaboration equation based on age, sex, race and outpatient serum creatinine.29 Race/ethnicity was categorised as white, black or other (Latino, Asian, Native American or other racial/ethnic minority groups). Comorbidities except for hepatitis C and HIV were assigned on the basis of relevant ICD-9-CM (the International Classification of Diseases, Ninth Revision, Clinical Modification) diagnostic and procedure codes and Current Procedural Terminology (CPT) codes in the VA Medical SAS data sets.2 30–33 Hepatitis C and HIV were assigned based on laboratory results." http://bmjopen.bmj.com/content/7/6/e015735 http://bmjopen.bmj.com/content/7/6/e015735 That all said, this journal doesn't have a great impact factor (2.37), so this definitely falls under "huh, this warrants further study."
marklyon 9y ago
WARNING: Linked site may have malware injected into some of its ads.
MR4D 9y ago
Sentences like this make me question everything about the article (and taint the research by association): "Use of the drugs was associated with a 25 percent greater risk of death," Given that we all have a 100% chance of death, what does this mean?

56 points by rezaprima 9y ago

What did (or didn't) this study control for? I appreciate them stopping short of saying that proton pump inhibitors kill people, but without a causal mechanism it seems more plausible that chronic use is correlated with other life-shortening factors.

andy_ppp 9y ago
There’s an obvious issue that you stomach acid is there to digest food correctly and also provide the environment for growing the correct microbiome; both of which are pretty vital functions I’d say.
TillE 9y ago
They didn't find a similar effect with H2 blockers, which pretty strongly suggests a specific problem caused by the mechanism of PPIs.
- tpeo 9y ago
  Only if the choice between PPI and H2 blockers is random. If there's some self-selection going on, there isn't much to say about PPI's impact on patient health given what we know about H2.
somethingawful 9y ago
Yeah, lots of risk for confounders and selection bias in a study like this. If you take the huge number of patients with a history of GI bleeding (for which PPI therapy is well-proven), those are patients who already have an elevated all-cause mortality risk. They also selected patients who had at least one creatinine measure in their EHR; so probably people who are more likely to have background renal disease. And using US veterans makes it hard to generalize to the greater population. However, they also saw elevated risk in patients who didn't have a de-facto indication for PPIs (GERD, GI bleeding, etc), so maybe there is something to this. Honestly, it's kind of an amateur study design. I think the conclusion to draw here is we need a large randomized control study to look at this issue. Regardless, as a physician, I agree with the study authors that if a patient doesn't have a specific indication for PPI, they shouldn't be on one. Then again, I don't need a study to tell me that; it's my feeling about ALL medications.
ozi 9y ago
This study is bogus because they didn't analyze cause of death or account for the reason for using PPI. H2 blockers and PPIs are often not prescribed for the same things. For many serious diseases PPIs are commonly prescribed as a secondary medication (eg with Plavix) where H2 blockers would make no sense. That's why the group sizes differ greatly.

danjoc 9y ago

... in a small, biased sample.

tpeo 9y ago
Biased, maybe. But the sample sizes are pretty big, whether "bigness" refers either to absolute numbers or to being big enough such that whatever they're estimating will come pretty close to the true value of that variable for similar populations. I mean, the smallest sample is 70k plus.
charlesism 9y ago
No, but as always they trot out the relative numbers. > "25% greater risk of death, compared with H2 blockers" Whether that means anything to me depends on what my odds of dying are on H2 blockers. If it's 1 in 3 then I care. If it's 1 in 3,000,000 then I don't.

greglindahl 9y ago

PPIs are pretty difficult to stop taking -- I started taking Prilosec in 2004 for reflux and after a few tries at stopping abruptly resulted in horrid symptoms, I finally manged to tail off by reducing the dose 1/8 at a time every 2 weeks, over a total period of 2 months. From all accounts H2 blockers are easier to quit. I was pleasantly surprised that I didn't have any heartburn or reflux issues when I was done -- apparently the original cause was gone.

jgalt212 9y ago
This has been my experience as well. I found it helpful to taper the Prilosec, and move over the seemingly less dangerous Pepcid. And then taper the Pepcid to 0.
notadoc 9y ago
Did you adjust your diet during that period of time? What do you think was the original cause?

tpeo 9y ago

What if PPI users are more likely to have some other health issues compared to other patients due to some unobserved variable (e.g. lifestyle, strength of the physiological reaction to stress, genetic factors affecting both the likelihood of becoming a PPI user as well as the likelihood of having other health issues)? Oh, man... correlational studies... shame they didn't directly link to the article, too.

Ocerge 9y ago

Getting off of PPIs is a miserable experience. It gave me the worst acid reflux of my life, lasting almost a whole month. Everything is back to normal now (I don't think I should have been taking them in the first place), but I wonder if the crappy withdrawal process contributes to this somehow.

senectus1 9y ago
I've been on them for about 10 years, for the last few years I've halved the dosage. I might have to talk to the bonesaw about halving it again with the intention of getting off them. my experience though is that if I stop taking them I get it pretty bad and my energy levels go right out the window. I just become sloth like all day every day and cant think worth a damn.
- ppiuser 9y ago
  > I just become sloth like all day every day and cant think worth a damn. A heartburn session and brain fog seem to be linked imo.

ppiuser 9y ago

Not something I enjoy reading after being on lansoprazole for around 8 years for heartburn. I decided to get off them with dietary changes a couple years back after reading how they are approved for short term doses and long term effects were untested. Doctors never showed much interest in discovering and treating the cause of the acid problem and even found it odd that I was trying to get off the tablets. I haven't been able to find if the damage they potentially cause in areas beyond the stomach reverses over time.

senectus1 9y ago
so how are you controlling the burn now?
- greglindahl 9y ago
  After you've been on a PPI for a long time, you probably don't have heartburn anymore for the original reason. After I tailed off I occasionally have a throat spasm, but no reflux. If I did have significant heartburn or reflux again I'll definitely use an H2 blocker, and only for a short period of time.
- ppiuser 9y ago
  Through trial and error I came to a low-carb(/low GI?) paleo style diet which seems to be inline with what other suggest. Alcohol, sugar and even stress definitely make it worse for me at least. edit: Special occasions where I might indulge in the above triggers I'll end up using an antacid for a day or two.

ianai 9y ago

They're talking about millions of data points. They could probably find significant correlations between anything at that point.

robert_foss 9y ago
Instances sure, but statistically significant correlations most likely not.

senectus1 9y ago

It bugs me that they just say "risk of death" which could mean anything; being shot, dying in a car accident, getting cancer having a heart attack... which is ridiculous I mean they do mention food poisoning and dementia etc but nothing about which of these factor strongly against the numbers of those that died. Is the food poisoning numbers effected by the poor nutritional practices (obese buffet eating crowds?), I know that many PPI takers are on the drug due to poor eating habits, where others are on it despite excellent eating habits. Also, a common reason for dementia symptoms is B12 deficiency which is a known problem with PPI and common advice for those taking it is to bump their intake of Vit B12. so really.. this study is looking very loosey goosey to me.

arnoooooo 9y ago

Suffering from acid reflux, I read at some point (I guess it was on Mayo Clinic) that something like 80% of people diagnosed as producing too much acid actually produce too little. Since stomach valves are pH activated, having too little acid causes the valves not to clause, which can result in reflux or downstream acid leakage. I tested this by taking HCL supplements, which did fix the issue.

dustinmr 9y ago
Would love to read the study if you can find it.
ipunchghosts 9y ago
> read at some point (I guess it was on Mayo Clinic) I would strongly suggest checking your sources. Many internet "doctors" aka charlatans, state low acid is a problem. I asked my doctors at John Hopkins about this and they said it was bunk.
raarts 9y ago
I tried that too. But it made no difference whatsoever.

kazinator 9y ago

Is that a higher death rate compared to the entire population which includes people who have no need for these blockers? Or compared to just those who need the blockers just as much as the users, but don't use them?

aladoc99 9y ago

Looking at the article in BMJ Open, I don't see that they controlled for obesity, either by BMI or any other measure. This is a huge confounder, making reflux symptoms worse and being an independent predictor of mortality. If I'm right, this is a huge oversight on their part.

jawilson2 9y ago
"External adjustment to estimate the impact of three unmeasured confounders, including obesity, smoking and use of therapeutics including anticoagulants, antiplatelet agents and non-steroidal anti-inflammatory drugs, shows a net confounding bias of 9.66% (see online supplementary figure 5). The total bias could move a null association between PPI and death from HR 1.00 to HR 1.10 (reflecting the net positive bias of 9.66% rounded up to 10.0%). The association we observed between PPI and death was 1.25>1.10, which cannot be fully due to bias of unmeasured confounding." "Covariates included age, race, gender, eGFR, number of outpatient serum creatinine measurements, number of hospitalisations, diabetes mellitus, hypertension, cardiovascular disease, peripheral artery disease, cerebrovascular disease, chronic lung disease, cancer, hepatitis C, HIV, dementia and diseases associated with acid suppression therapy use such as gastro-oesophageal reflux disease (GERD), upper gastrointestinal (GI) tract bleeding, ulcer disease, Helicobacter pylori infection, Barrett’s oesophagus, achalasia, stricture and oesophageal adenocarcinoma.25–28 eGFR was calculated using the abbreviated four-variable CKD epidemiology collaboration equation based on age, sex, race and outpatient serum creatinine.29 Race/ethnicity was categorised as white, black or other (Latino, Asian, Native American or other racial/ethnic minority groups). Comorbidities except for hepatitis C and HIV were assigned on the basis of relevant ICD-9-CM (the International Classification of Diseases, Ninth Revision, Clinical Modification) diagnostic and procedure codes and Current Procedural Terminology (CPT) codes in the VA Medical SAS data sets.2 30–33 Hepatitis C and HIV were assigned based on laboratory results." http://bmjopen.bmj.com/content/7/6/e015735 http://bmjopen.bmj.com/content/7/6/e015735 That all said, this journal doesn't have a great impact factor (2.37), so this definitely falls under "huh, this warrants further study."

marklyon 9y ago

WARNING: Linked site may have malware injected into some of its ads.

MR4D 9y ago

Sentences like this make me question everything about the article (and taint the research by association): "Use of the drugs was associated with a 25 percent greater risk of death," Given that we all have a 100% chance of death, what does this mean?