Daily Low-Dose Aspirin, Round 2

by [anonymous]1 min read21st Mar 201221 comments

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(For Round 1, see this comment from last year.)

NYT: Studies Link Daily Doses of Aspirin to Reduced Risk of Cancer

One of the new studies examined patient data from dozens of large, long-term randomized controlled trials involving tens of thousands of men and women. Researchers at the University of Oxford found that after three years of daily aspirin use, the risk of developing cancer was reduced by almost 25 percent when compared with a control group not taking aspirin. After five years, the risk of dying of cancer was reduced by 37 percent among those taking aspirin.

A second paper that analyzed five large randomized controlled studies in Britain found that over six and a half years on average, daily aspirin use reduced the risk of metastatic cancer by 36 percent and the risk of adenocarcinomas — common solid cancers including colon, lung and prostate cancer — by 46 percent.

The article is worth reading in its entirety, but here's an especially interesting paragraph:

The new studies, however, also found that the risk of bleeding in aspirin users diminished over time, and that the risk of death from brain bleeds was actually lower in the aspirin users than in the comparison group.

The evidence still isn't perfect, but the purpose of rationality is making good decisions with limited information. I am a healthy 28-year-old and these studies make me even more confident that taking daily low-dose aspirin is the right thing for me to do.

On a related note, if society were more rational, I wouldn't have to be sad reading paragraphs like this one:

Some cancer doctors commended the new research, saying said that despite the limitations of the analyses, no other long-term clinical trials of aspirin and cancer are likely to be done because of the enormous expense involved and the fact that aspirin is a cheap generic drug.

Or these ones from A Cheap Drug Is Found to Save Bleeding Victims, published on the same day:

For months, a simple generic drug has been saving lives on America’s battlefields by slowing the bleeding of even gravely wounded soldiers.

Even better, it is cheap. But its very inexpensiveness has slowed its entry into American emergency rooms, where it might save the lives of bleeding victims of car crashes, shootings and stabbings — up to 4,000 Americans a year, according to a recent study.

Because there is so little profit in it, the companies that make it do not champion it.

 

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  1. First study fulltext: Rothwell et al 2012, "Short-term effects of daily aspirin on cancer incidence, mortality, and non-vascular death: analysis of the time course of risks and benefits in 51 randomised controlled trials" http://www.istudymedicine.com/wp-content/uploads/aspirin.pdf
  2. Second: Rothwell et al 2011, "Effect of daily aspirin on long-term risk of death due to cancer: analysis of individual patient data from randomised trials" http://www.beppegrillo.it/immagini/Aspirin%20and%20death%20from%20cancer%20\(Lancet%202010\).pdf

Now that these are available, I've read through them and specifically looked at any mentions of all-cause mortality; while most of the all-cause figures are not statistically-significant, in every case the point-value seems to be consistently lower (ie. the baby aspirin was helpful). I didn't find any all-cause numbers cited in which the aspirin group died more.

I was critical in the earlier discussion because we weren't seeing the all-cause numbers and there are excellent reasons to be wary of medical results, but personally I find all-cause mortality to be a very persuasive metric, and in the absence of any contraindications for myself or finding that the all-cause numbers have been fudged, I think I'll start low-dose/baby aspirin. My main worry is that most of these studies only deal with older people and the benefits might be negative in younger people, but it also looks like the effect is cumulative so one might want to start early. (The medical aspects are my only concern - money-wise, it might as well be free; for example, here on Amazon is 730 tablets or 2 years' worth for $8.)

A large recent trial appears to show that low-dose aspirin isn't helpful, and may be harmful, for healthy older people.

Are you now taking low-dose aspirin?

Thanks dawg, low-dose aspirin and Vitamin D it is for me as well. Your comment had an impact.

baby aspirin

No aspirin for kids, Holmes.

I think the name simply stuck from when they did still give aspirin to kids at all. :)

As far as I remember, "baby aspirin" just meant a small one = low-dose aspirin.

It appears that the evolutionarily unprecedented high omega-6 and low omega-3 intake in the modern western diet causes excessive series-2 prostaglandin and thromboxane (TXA2) formation, and resulting inflammation and cardiovascular effects- and low dose aspirin is an attempt to combat this. Why not fix the problem at it's source?

Reducing omega-6 oils in your diet and increasing omega-3 should have a similar effect, but with more proven safety and effectiveness: nearly all humans did this until industrial seed oils became popular in the last few decades (see this video series from biochemist Dr. Bill Lands for more details http://youtu.be/dgU3cNppzO0 ).

Aspirin works primarily by suppressing production of thromboxane and inflammatory series-2 prostaglandins from omega-6 fats, by inactivating the cyclooxygenase enzymes (COX-1, and COX-2). Omega-3 fats also competitively inhibit this same enzyme, by competing with omega-6 fats to be metabolized into less inflammatory series-1 and series-3 prostaglandins.

There are other important benefits of fixing the omega 3/6 ratio in your diet as well- their ratio is reflected in tissue lipid membranes, and likely influences the proper function of these membranes. Continuing on a high omega-6 diet and trying to counter-act this with aspirin seems less than ideal.

It would be interesting to see some data showing the effectiveness of low dose aspirin in countries that already have a healthy omega 3/6 ratio (such as Greenland or Japan). I would be very surprised if it still has the same benefit in such a group.

As a person who has a nearly 1/1 omega-6 to long chain omega-3 ratio in my diet (I regularly eat fatty cold water fish and avoid seed oils), I wouldn't consider low dose aspirin to be a prudent risk adverse decision unless I saw data showing it's benefits reproduced in others with a similar intake ratio.

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I retracted this, because I have learned a lot more about this issue in the last year. I am still undecided on aspirin, however I no longer think that the mechanisms mentioned above are the only important roles aspirin plays. I am also no longer convinced that omega-3 offers a health benefit, and that omega-6 restriction alone may be superior to replacing omega-6 with omega-3.

If you look at the Rothwell paper linked above by gwern, there's one Japanese study there - JPAD (Ogawa H, Nakayama M, Morimoto T, et al. Japanese Primary Prevention of Atherosclerosis With Aspirin for Diabetes (JPAD) Trial Investigators. Low-dose aspirin for primary prevention of atherosclerotic events in patients with type 2 diabetes: a randomized controlled trial. JAMA 2008; 300: 2134–41).

Looking at the graphs, JPAD effectively showed zero effect of aspirin. I think this supports your thesis.

But from JPAD, the specific effects that are supposed to show aspirin benefits weren't what this study measured! They were looking at:

Primary end points were atherosclerotic events, including fatal or nonfatal ischemic heart disease, fatal or nonfatal stroke, and peripheral arterial disease.

This doesn't include anything related to cancer. And to the extent that the study did look at all-cause mortality, it showed exactly what you would expect from a relatively small (n=2539) and short ("median follow-up of 4.37 years") trial where aspirin was yielding benefits: a large but non-statistically-significant effect

A total of 34 patients in the aspirin group and 38 patients in the nonaspirin group died from any cause (HR, 0.90; 95% CI, 0.57-1.14; log-rank test, p=.67).

I haven't looked at the JPAD paper yet, but that Cochrane study plots JPAD results for cancer endpoints as well as major vascular and extracranial bleeds. In the same graphs I don't see large effects.

It's worth pointing out the general low cancer rates (in the controls as well) in the JPAD study.

I would be worried about what that might do to your digestive system.

From what I've read, the low dose (80 mg) has almost no effect on the digestive system, compared to the normal dose (325 mg) that people usually take.

New review, trying to quantify population benefits: "Estimates of benefits and harms of prophylactic use of aspirin in the general population", Cuzick et al 2014

Background: Accumulating evidence supports an effect of aspirin in reducing overall cancer incidence and mortality in the general population. We reviewed current data and assessed the benefits and harms of prophylactic use of aspirin in the general population.

Methods: The effect of aspirin for site-specific cancer incidence and mortality, cardiovascular events was collated from the most recent systematic reviews. Studies identified through systematic Medline search provided data regarding harmful effects of aspirin and baseline rates of harms like gastrointestinal bleeding and peptic ulcer.

Results: The effects of aspirin on cancer are not apparent until at least 3 years after the start of use, and some benefits are sustained for several years after cessation in long-term users. No differences between low and standard doses of aspirin are observed, but there were no direct comparisons. Higher doses do not appear to confer additional benefit but increase toxicities. Excess bleeding is the most important harm associated with aspirin use, and its risk and fatality rate increases with age. For average-risk individuals aged 50–65 years taking aspirin for 10 years, there would be a relative reduction of between 7% (women) and 9% (men) in the number of cancer, myocardial infarction or stroke events over a 15-year period and an overall 4% relative reduction in all deaths over a 20-year period.

Conclusions: Prophylactic aspirin use for a minimum of 5 years at doses between 75 and 325 mg/day appears to have favourable benefit–harm profile; longer use is likely to have greater benefits. Further research is needed to determine the optimum dose and duration of use, to identify individuals at increased risk of bleeding, and to test effectiveness of Helicobacter pylori screening–eradication before starting aspirin prophylaxis.

(Seems to ignore all-cause mortality and otherwise feels a bit scattershot.)

Regular aspirin use linked to "wet" macular degeneration, which can cause blindness - http://www.webmd.com/eye-health/news/20130118/aspirin-blinding-eye-disease

Weak evidence, not randomized.

3 new pieces of information to consider:

http://www.ncbi.nlm.nih.gov/pubmed/9732917

Found that background rates of non-H. pylori, non-NSAID-induced Ulcers might be higher than we previously believed.

http://www.ncbi.nlm.nih.gov/pubmed/23070505 & http://www.ncbi.nlm.nih.gov/pubmed/23121403

Found no increase in the risk for GI bleeding in patients taking long-term Aspirin.

FYI: The US Preventive Services Task Force recommends against the routine use of aspirin and nonsteroidal anti-inflammatory drugs (NSAIDs) to prevent colorectal cancer in individuals at average risk for colorectal cancer. The main negative effects are gastrointestinal bleeding.

Looking at all-cause mortality (rather than colorectal cancer in isolation) might drastically change the analysis, but I'm not aware of such research having been done. Closest I've come across relates to the Cardiovascular Polypill.

From OP:

The new studies, however, also found that the risk of bleeding in aspirin users diminished over time, and that the risk of death from brain bleeds was actually lower in the aspirin users than in the comparison group.

Wonder how they controlled for survivorship.

In the United States, two major studies of low-dose aspirin to prevent cancer did not find reductions in cancer with aspirin use. Those findings were excluded from analysis by the Oxford researchers because they involved use of aspirin every other day, rather than daily use.

In the first study, the dose was 100mg, so average 50mg a day, and in the second, 325mg for average 162mg

Wonder how they controlled for survivorship.

If they're doing it right, cumulative mortality rates ought to solve that problem.

On a related note, if society were more rational, I wouldn't have to be sad reading paragraphs like this one:

Some cancer doctors commended the new research, saying said that despite the limitations of the analyses, no other long-term clinical trials of aspirin and cancer are likely to be done because of the enormous expense involved and the fact that aspirin is a cheap generic drug.

On a completely tangential note if you were more rational you wouldn't have to be sad reading paragraphs like that one either. It doesn't seem to be of much practical benefit.