low dose aspirin and colon cancer risk

The case for aspirin use for primary prevention of cardiovascular disease is a bit of a toss-up. However, there may be additional roles for aspirin (and NSAIDs) in cancer prevention (see aspirin and colon cancer annals2015 in dropbox, or doi:10.7326/M15-0039). Over the past 20-30 year, there have been many studies in animals showing a potential benefit of aspirin and NSAIDs in preventing colorectal neoplasia. And many observational studies in humans have found a reduced risk of colorectal cancer. More data is needed, though one of the lingering questions is the dose of aspirin associated with decreased colorectal cancer. This current study cross-references the Danish cancer registry with the pharmacy registry, with pretty complete data.

Details:

--population-based cohort study of people in Northern Denmark, comparing aspirin and NSAID use in 10,280 cases of documented colorectal cancer with 102,800 controls, between the years of 1994-2011

--in Denmark, there is a pretty complete registry of patients with histologically-verified first diagnosis of colorectal cancer; also, >90% of total sales of low-dose aspirin are prescriptions and tracked in their systems. Of the NSAIDs, only ibuproben 200mg (15% of total Danish sales of NSAIDs) is over-the-counter, so the vast majority are tracked.

--median age 69.8, 54.8% male, 78% never used low-dose ASA, 54% never used NSAIDs, 12% on hormone replacement therapy, 15% statins, 7% diabetic, 20% with rheumatologic disease, 19% cardiovascular dz

Results:

--those continuously taking low-dose aspirin (75,100, or 150mg/d)  for >5 years had a 27% reduction in colorectal cancer risk [OR 0.73 (0.54-0.99)]

--those taking NSAIDs consistently for >5 years esp at the highest doses, had a 36% reduction in colorectal cancer risk [OR 0.64 (0.52-0.80)], and especially so in those NSAIDs with significant COX-2 selectivity

--the data for ever-use (ie, not taking continuously) was non-significant for aspirin, but significant for NSAIDs (6% risk reduction)

so, how does one piece this all together??? 

--the data on cancer is largely from observational studies (and therefore susceptible to lots of biases), though the Danish one seems to be pretty tight. i am adding some of my older blogs at the end here, to reference some of these older cancer studies. It is notable that the aspirin data in the Danish study found potential effectiveness in those on low-dose aspirin. Their data on NSAIDs is also pretty strong and consistent with older data, though i would argue that NSAIDs have lots of other adverse effects (blood pressure, heart failure, renal failure...), and the most effective ones (COX-2 selective) are pretty consistently bad for the heart.

--there have been several primary prevention studies in the use of aspirin for cardiovascular disease. Overall, the data, in this pretty low risk group (as opposed to secondary prevention studies) is: there is a significant 20% decrease [RR 0.80 (0.67-0.96)] in risk of first nonfatal MI, and non significant decreases in total mortality and stroke, but a 54% increase in major extracranial bleeds [RR 1.54(1.30-1.82)] and a 12% decrease in cancer incidence [RR 0.88(0.80-0.98)]. For example these numbers translate to -- for a 60 yo man over 10 years: 

            --at low cardiovasc risk: 5 fewer nonfatal MIs, 4 more significant extracranial bleeds

            --at mod cardiovasc risk (eg 10-yr risk of about 5%): 17 fewer nonfatal MIs, 16 more significant extracranial bleeds, approx 1 more intracranial bleed

            --at high cardiovasc risk (10-year risk of about 10%): 27 fewer nonfatal MIs, 22 more significant extracranial bleeds, approx 1 more intracranial bleed

            --at low cancer risk: 1 fewer cancers

            --at mod cancer risk: 6 fewer cancers

            --at high cancer risk: 12 fewer cancers

--as with most things patient-wise, it is useful to look at the individual instead of the aggregate data. Those in the primary prevention group who are healthy, active, have no risk factors, are at low risk for cancer, probably should not be on aspirin. those on the opposite end of the spectrum (no cardiovasc disease, but smoker with lots of other risk factors; or at high risk of cancer) probably should be. All patients should get a sense of the risks and benefits, taking into account where they are in the spectrum of potential disease (heart has the best data, though I do include cancer risk) along with how they value potential outcomes (eg longterm potential protection from cancer and heart disease, esp nonfatal MI) vs risk of major bleed, including the much lower risk of intracranial hemorrhage.

here are the older blogs:

http://gmodestmedblogs.blogspot.com/2014/05/fda-against-aspirin-for-primary.html  raises the issue of cancer prevention as part of the equation of its use in primary prevention

http://gmodestmedblogs.blogspot.com/2014/02/2-articles-on-aspirin-and-colonbreast.html has 2 studies: one showing decreased cancer mortality, the other decreased metastatic disease

http://gmodestmedblogs.blogspot.com/2014/02/aspirin-decreases-risk-of-ovarian-cancer.html finding decreased ovarian cancer

http://gmodestmedblogs.blogspot.com/2014/02/aspirin-use-and-prostate-cancer.html  finding decreased prostate cancer metastases and mortality