Large & Unflattering Study On Aspirin

[Jem Oz]

Just read this. A very dim conclusion was reached about aspirin having no discernible impact on health/longevity in the elderly. 19,000 participants.

Any thoughts? My understanding about aspirin was that it's such a wildly positive substance, even if you had a range of health problems or weren't doing anything else that was pro-health, aspirin would still have a noticeable impact.

Costs of daily aspirin may outweigh its benefits, study finds

 

[mujuro]

Here’s the study

NEJM - Error

Weird formatting. Link still works for me. Where did WestsidePUFA go? He loved these kinds of studies /s

 

[Herbie]

They only tested for physical disability and demensia and said the people were healthy.

This is quite vague, physical disability was not defined as far as I saw when I briefly scrolled through. Is cancer a physical disability? Health was defined as not having dementia yet and not having a physical disability.

It was funded by cancer money.

It was only 100mg dose given to people eating pufa for decades.

 

[yerrag]

They only tested for physical disability and demensia and said the people were healthy.

This is quite vague, physical disability was not defined as far as I saw when I briefly scrolled through. Is cancer a physical disability? Health was defined as not having dementia yet and not having a physical disability.

It was funded by cancer money.

It was only 100mg dose given to people eating pufa for decades.

And I'm pretty sure the aspirin they used is the kind with so many excipients in it. If you look at the many kinds of aspirin being sold, you will be hard put to find the kind that has only cornstarch (and aspirin). All the rest are filled with excipients of all kinds. It makes me wonder why those excipients are ever added. Is it to contaminate aspirin with all sorts of allergenic substances so that when the doctor asks you "Are you allergic to aspirin?" you will likely say yes and you will be given something "better" which of course costs more and has more side-effects.

Are you allergic to "excipients" or are you allergic to aspirin? Really.

 

[mujuro]

It was only 100mg dose given to people eating pufa for decades.

Seriously. The participants were over 65. How much can we expect this age group to improve, let alone on a trivial dose of 100mg?

 

[Mito]

Effect of Aspirin on All-Cause Mortality in the Healthy Elderly

BACKGROUND
In the primary analysis of the Aspirin in Reducing Events in the Elderly (ASPREE) trial, now published in the Journal, we report that the daily use of aspirin did not provide a benefit with regard to the primary end point of disability-free survival among older adults. A numerically higher rate of the secondary end point of death from any cause was observed with aspirin than with placebo.

METHODS
From 2010 through 2014, we enrolled community-dwelling persons in Australia and the United States who were 70 years of age or older (or ≥65 years of age among blacks and Hispanics in the United States) and did not have cardiovascular disease, dementia, or disability. Participants were randomly assigned to receive 100 mg of enteric-coated aspirin or placebo. Deaths were classified according to the underlying cause by adjudicators who were unaware of trial-group assignments. Hazard ratios were calculated to compare mortality between the aspirin group and the placebo group, and post hoc exploratory analyses of specific causes of death were performed.

RESULTS
Of the 19,114 persons who were enrolled, 9525 were assigned to receive aspirin and 9589 to receive placebo. A total of 1052 deaths occurred during a median of 4.7 years of follow-up. The risk of death from any cause was 12.7 events per 1000 person-years in the aspirin group and 11.1 events per 1000 person-years in the placebo group (hazard ratio, 1.14; 95% confidence interval [CI], 1.01 to 1.29). Cancer was the major contributor to the higher mortality in the aspirin group, accounting for 1.6 excess deaths per 1000 person-years. Cancer-related death occurred in 3.1% of the participants in the aspirin group and in 2.3% of those in the placebo group (hazard ratio, 1.31; 95% CI, 1.10 to 1.56).

CONCLUSIONS
Higher all-cause mortality was observed among apparently healthy older adults who received daily aspirin than among those who received placebo and was attributed primarily to cancer-related death. In the context of previous studies, this result was unexpected and should be interpreted with caution. (Funded by the National Institute on Aging and others; ASPREE ClinicalTrials.gov number, NCT01038583.)

NEJM - Error

 

[yerrag]

Effect of Aspirin on All-Cause Mortality in the Healthy Elderly

BACKGROUND
In the primary analysis of the Aspirin in Reducing Events in the Elderly (ASPREE) trial, now published in the Journal, we report that the daily use of aspirin did not provide a benefit with regard to the primary end point of disability-free survival among older adults. A numerically higher rate of the secondary end point of death from any cause was observed with aspirin than with placebo.

METHODS
From 2010 through 2014, we enrolled community-dwelling persons in Australia and the United States who were 70 years of age or older (or ≥65 years of age among blacks and Hispanics in the United States) and did not have cardiovascular disease, dementia, or disability. Participants were randomly assigned to receive 100 mg of enteric-coated aspirin or placebo. Deaths were classified according to the underlying cause by adjudicators who were unaware of trial-group assignments. Hazard ratios were calculated to compare mortality between the aspirin group and the placebo group, and post hoc exploratory analyses of specific causes of death were performed.

RESULTS
Of the 19,114 persons who were enrolled, 9525 were assigned to receive aspirin and 9589 to receive placebo. A total of 1052 deaths occurred during a median of 4.7 years of follow-up. The risk of death from any cause was 12.7 events per 1000 person-years in the aspirin group and 11.1 events per 1000 person-years in the placebo group (hazard ratio, 1.14; 95% confidence interval [CI], 1.01 to 1.29). Cancer was the major contributor to the higher mortality in the aspirin group, accounting for 1.6 excess deaths per 1000 person-years. Cancer-related death occurred in 3.1% of the participants in the aspirin group and in 2.3% of those in the placebo group (hazard ratio, 1.31; 95% CI, 1.10 to 1.56).

CONCLUSIONS
Higher all-cause mortality was observed among apparently healthy older adults who received daily aspirin than among those who received placebo and was attributed primarily to cancer-related death. In the context of previous studies, this result was unexpected and should be interpreted with caution. (Funded by the National Institute on Aging and others; ASPREE ClinicalTrials.gov number, NCT01038583.)

NEJM - Error

Did the study normalize to one form of aspirin? The one that has only cornstarch as a binder? Or did they omit that 'insignificant detail?'

 

[Mito]

Did the study normalize to one form of aspirin? The one that has only cornstarch as a binder? Or did they omit that 'insignificant detail?'

8.2 Drug packaging

A bulk supply of enteric-coated active and placebo tablets has been provided free of charge by Bayer Pharma AG. The medication will be packaged and labeled according to the randomization code. Participants will be provided with a 12 month supply on each occasion. Packaging will feature the name of the study (ASPREE clinical trial), sponsor, supplier, batch number, expiry date, contents, the fact that the content is pharmacy medicine for use in clinical trials only, instructions for use, and a warning to keep out of reach of children. Each medication container will be labeled with a pre-printed, unique medication Identification (ID) Number. Once dispensed, this number will also be recorded in the participant’s file in the Study Drug Accountability Log.

https://aspree.org/usa/wp-content/u.../ASPREE-Protocol-Version-9_-Nov2014_FINAL.pdf

 

[yerrag]

8.2 Drug packaging

A bulk supply of enteric-coated active and placebo tablets has been provided free of charge by Bayer Pharma AG. The medication will be packaged and labeled according to the randomization code. Participants will be provided with a 12 month supply on each occasion. Packaging will feature the name of the study (ASPREE clinical trial), sponsor, supplier, batch number, expiry date, contents, the fact that the content is pharmacy medicine for use in clinical trials only, instructions for use, and a warning to keep out of reach of children. Each medication container will be labeled with a pre-printed, unique medication Identification (ID) Number. Once dispensed, this number will also be recorded in the participant’s file in the Study Drug Accountability Log.

https://aspree.org/usa/wp-content/u.../ASPREE-Protocol-Version-9_-Nov2014_FINAL.pdf

Exactly.

Bayer 81 mg Enteric Coated

Inactive Ingredients: black iron oxide, brown iron oxide, carnauba wax, cornstarch, D&C yellow #10, aluminum lake, FD&C yellow #6, aluminum lake, hypromellose, methacrylic acid copolymer type C, polysorate 80, powedered cellulose, propylene glycol, shellac, sodium lauryl sulfate, triacetin, triethyl citrate.

compare it with

Gericare 325 mg Aspirin

Inactive Ingredient: Cornstarch

 

[Mito]

ASPREE (ASPirin in Reducing Events in the Elderly)

• ASPREE is the largest primary prevention aspirin study ever undertaken in healthy older people.
• It will determine whether daily low dose aspirin prevents or delays the onset of age-related illness such as cardiovascular disease (heart attack and stroke), dementia, depression and certain cancers and if the benefits outweigh the risks, such as bleeding.
• ASPREE is a randomized, double-blind placebo controlled study.
• It involves American males and females, 65 years of age and older.
• Participants are randomly assigned (or randomized) to take either a low-dose aspirin tablet (100mg) or a matching placebo tablet (dummy pill) for an average of 5 years.
• The study has enrolled 19,113 healthy participants in more than 36 locations in the US and throughout south-eastern Australia.
• Annual visits involve a number of health, clinical and other measurements. Significant abnormalities will be reported to the participant’s provider for clinical follow up.
• The trial has a number of sub-studies, which investigate the effect of aspirin on specific diseases.
• ASPREE is funded by the US and Australian governments.
• The Berman Center for Outcomes and Clinical Research leads the trial in the US, and Monash University leads the trial in Australia.
• Results of the principal ASPREE study should be known in 2018.

The outcome of the trial?

• If aspirin is shown to be of overall benefit, millions of healthy older people around the world will be advised to take aspirin.
• If aspirin is shown not to be of benefit, then many older people will stop taking an unnecessary medication.

Don’t we already know enough about aspirin?

Aspirin is often prescribed for ‘secondary prevention’ in people who have had a heart attack or stroke because research demonstrates that in this instance, the benefit of preventing another heart attack or stroke clearly outweighs the risks, such as bleeding. Other studies indicate that aspirin may help prevent or delay the onset of cardiovascular disease, dementia, depression and some types of cancer from happening in the first place. However, this has never been proven.


Many world health authorities are reluctant to recommend that healthy older people take low-dose aspirin for ‘primary prevention’ (to prevent a first heart attack or stroke), not because the risks are higher – people taking aspirin for secondary prevention are also at risk of side-effects – but because there is a lack of evidence about aspirin’s overall benefit in older, healthy people. Very few primary prevention aspirin studies have included people aged over 70. For the first time, ASPREE will weigh the potential benefits versus the potential risks, in healthy older people.

People are also living longer. If life expectancy continues along the same trajectory as history, it is predicted that 50% of Australian babies born today will live to be over 100. At the heart of the ASPREE study is a goal to discover how to maintain years of good quality life within that increased lifespan. This is why the ASPREE study is so important: the trial focuses only on older people, aiming to discover how to maintain years of good quality of life through disease prevention. The results will be relevant to many aging people around the world.

ABOUT US - Aspree USA

 

[yerrag]

• If aspirin is shown not to be of benefit, then many older people will stop taking an unnecessary medication.

And what will they replace it with? By any chance, will they replace it with something 'better?' Something that an 'expert' will recommend? Less side-effects and less expensive?

Other studies indicate that aspirin may help prevent or delay the onset of cardiovascular disease, dementia, depression and some types of cancer from happening in the first place. However, this has never been proven.

Is this true or just them saying it? @haidut @Travis ?

And lastly, 100mg of aspirin is, like earlier posted had said, so small an amount. And I'd add, what else are they taking as drugs that have more an effect on their health than a paltry amount of aspirin?

 

[Mito]

And lastly, 100mg of aspirin is, like earlier posted had said, so small an amount.

But a small amount should have some benefits and not the opposite?

And I'd add, what else are they taking as drugs that have more an effect on their health than a paltry amount of aspirin?

I don’t see other medications included on the exclusion list on page 20 (https://aspree.org/usa/wp-content/u.../ASPREE-Protocol-Version-9_-Nov2014_FINAL.pdf) but they claim to use healthy participants. I’m not an expert on randomized, double-blind, placebo controlled studies, but shouldn’t the “effects” of other medications be “randomized out” so as to affect both the aspirin and control group equally?

 

[yerrag]

But a small amount should have some benefits and not the opposite?
I don’t see other medications included on the exclusion list on page 20 (https://aspree.org/usa/wp-content/u.../ASPREE-Protocol-Version-9_-Nov2014_FINAL.pdf) but they claim to use healthy participants. I’m not an expert on randomized, double-blind, placebo controlled studies, but shouldn’t the “effects” of other medications be “randomized out” so as to effect both the aspirin and control group equally?

Thanks for checking on that. I'm not sure if their definition of healthy is well-defined at all. If they were to use it on a group that is healthy enough to not need any prescription drugs, I would be more inclined to believe the premise and conclusion of the study. But I think we both know that not taking any prescription medication would be a difficult descriptor to fit for the general population, much less for the older subset. I'm neither an expert on statistics, but I can imagine the population in the study to be users of prescription drugs, and if they are defining their health based on insurance screening metrics, I would say that those metrics produce plenty of false negatives. If I have hypertension, for example, I would have to take blood pressure medication to fall in line with healthy blood pressure numbers, in order to qualify for life insurance. But we both know that meeting the numbers is hardly a gauge for health, especially if those numbers were tweaked by the use of prescription drugs.

I also want to point out again how the Bayer 81mg Enteric Coated tablet compares with the Gericare 325mg Aspirin tablet, ingredient-wise:

Bayer 81 mg Enteric Coated Inactive Ingredients: black iron oxide, brown iron oxide, carnauba wax, cornstarch, D&C yellow #10, aluminum lake, FD&C yellow #6, aluminum lake, hypromellose, methacrylic acid copolymer type C, polysorate 80, powedered cellulose, propylene glycol, shellac, sodium lauryl sulfate, triacetin, triethyl citrate.

Gericare 325 mg Aspirin Inactive Ingredient: Cornstarch

Seeing how the Bayer product is constituted, would anybody in his right mind, devoid of any other consideratios, consider the Bayer aspirin to represent the drug called by that name?

 

[tankasnowgod]

Here's a study that shows that enteric coated aspirin isn't as effective as plain aspirin- Effect of enteric coating on antiplatelet activity of low-dose aspirin in healthy volunteers. - PubMed - NCBI

 

[Travis]

And what will they replace it with? By any chance, will they replace it with something 'better?' Something that an 'expert' will recommend? Less side-effects and less expensive?


Is this true or just them saying it? @haidut @Travis ?

And lastly, 100mg of aspirin is, like earlier posted had said, so small an amount. And I'd add, what else are they taking as drugs that have more an effect on their health than a paltry amount of aspirin?

There are many large trials showing a reduction in cancer with aspirin, but there's also reports of adult Reye syndrome. While it's true that aspirin will unequivocally and uniquely inhibit COX-2 by acetylation, this modification doesn't stop of the formation of alternative cyclooxygenase products. Aspirin-activated cyclooxygenase has 15-lipoxygenase activity on arachidonic and eicosapentaenoic acids forming epi-lipoxin A₄ and aspirin-triggered resolvin D, respectively, after subsequent hydroxylation from 5-lipoxygenase. Epi-lipoxin A₄ is somewhat like a leukotriene B₄ in form yet will actually reduce the migration of leukocytes, preventing an immunological response in that way. Aspirin has effects not shared by the other COX-2 inhibitors and the dosage seems to matter a good deal: Only a small amount of aspirin is needed for prostaglandin inhibition—apparently only ~100 mg/d for most people—yet larger doses are needed for significant leukocyte inhibition and increased nitric oxide synthesis. Two of three aforementioned effects would naturally lead to lower cancer rates, as observed, yet potentially at the price of enhanced infection by inhibiting innate immunity—which is also observed.

 

[haidut]

They only tested for physical disability and demensia and said the people were healthy.

This is quite vague, physical disability was not defined as far as I saw when I briefly scrolled through. Is cancer a physical disability? Health was defined as not having dementia yet and not having a physical disability.

It was funded by cancer money.

It was only 100mg dose given to people eating pufa for decades.

This. The study did not describe what they measured as "physical disability". The study also says that people with risk for CVD would still benefit from aspirin and so would people trying to prevent bowel cancer.
Half of the money came from the National Cancer Institute (NCI), which has been financing anti-aspirin propaganda for decades. Including that recent study on melanoma and aspirin that Peat wrote an entire newsletter about.

 

[Animalinstinct]

I also want to point out again how the Bayer 81mg Enteric Coated tablet compares with the Gericare 325mg Aspirin tablet, ingredient-wise:

Bayer 81 mg Enteric Coated Inactive Ingredients: black iron oxide, brown iron oxide, carnauba wax, cornstarch, D&C yellow #10, aluminum lake, FD&C yellow #6, aluminum lake, hypromellose, methacrylic acid copolymer type C, polysorate 80, powedered cellulose, propylene glycol, shellac, sodium lauryl sulfate, triacetin, triethyl citrate.

Gericare 325 mg Aspirin Inactive Ingredient: Cornstarch

Seeing how the Bayer product is constituted, would anybody in his right mind, devoid of any other consideratios, consider the Bayer aspirin to represent the drug called by that name?

Just to let you know that the very same Bayer Aspirin you're talking about has very different list of ingredients in Europe. The list is considerably shorter, and no iron oxides.

Edit: here's the list:

Cellulose, corn starch, copolymer C, natriumlaurylsuphate, polysorbat 80, talk, triecylate

 

[lollipop]

Just to let you know that the very same Bayer Aspirin you're talking about has very different list of ingredients in Europe. The list is considerably shorter, and no iron oxides.

Edit: here's the list:

Cellulose, corn starch, copolymer C, natriumlaurylsuphate, polysorbat 80, talk, triecylate

I noticed ingredient differences in US products while I was visiting Ireland. I ran out of my Emergen-c and saw some in a pharmacy in Dublin. The ingredients were vastly different; less chemicals in the US version, but this is only a vit-c supplement not aspirin. Wonder why the differences?

 

[Herbie]

It seems America gets the worst ingredients, ingredients must be good business in the states.

Australia and European versions of anything always seem to be safer, Coca Cola is a good example and Bayer aspirin in Australia and Europe have less ingredients. Norway has bayer aspirin which is swallowed Australia has bayer aspirin which is dissolved in water.

The low dose aspirin here is named Astrix and Cartia and are both enteric coated and marketing towards cardiovascular people.

 

[tankasnowgod]

Just to let you know that the very same Bayer Aspirin you're talking about has very different list of ingredients in Europe. The list is considerably shorter, and no iron oxides.

Edit: here's the list:

Cellulose, corn starch, copolymer C, natriumlaurylsuphate, polysorbat 80, talk, triecylate

Responding to this, the study I posted tested three different enteric coated aspirin products, and all three were less effective than regular uncoated aspirin.