Effect of daily aspirin on long-term risk of death due to cancer

[Willy50]

(interesting article, I wonder if it would impact in any way on HCC?  I also have read that limited aspirin intake acn reduce blood pressure, which may be helpful.  I've also read that the microbleeding associated with aspirin may over time reduce iron stores in the liver.  I've seen articles which claim it to be mildly antiviral as well. It may be worth asking your doctor what they think(!!!!! that last part especially true for advanced staging!!!!!! No self medicating!).  IF it reduces HCC (that's an IF; the article doesn't state it is a finding), then one may wonder if the anti-inflamatory aspects may reduce damage progression.  Too early to say, but interesting.  -Willy)

http://www.lancet.com/journals/lancet/article/PIIS0140-6736%2810%2962110-1/fulltext

The Lancet, Early Online Publication, 7 December 2010
doi:10.1016/S0140-6736(10)62110-1Cite or Link Using DOI
Effect of daily aspirin on long-term risk of death due to cancer: analysis of individual patient data from randomised trials
Prof Peter M Rothwell FMedSci a Corresponding AuthorEmail Address, Prof F Gerald R Fowkes FRCPE b, Prof Jill FF Belch FRCP c, Hisao Ogawa MD d, Prof Charles P Warlow FMedSci e, Prof Tom W Meade FRS f
Summary
Background
Treatment with daily aspirin for 5 years or longer reduces subsequent risk of colorectal cancer. Several lines of evidence suggest that aspirin might also reduce risk of other cancers, particularly of the gastrointestinal tract, but proof in man is lacking. We studied deaths due to cancer during and after randomised trials of daily aspirin versus control done originally for prevention of vascular events.
Methods
We used individual patient data from all randomised trials of daily aspirin versus no aspirin with mean duration of scheduled trial treatment of 4 years or longer to determine the effect of allocation to aspirin on risk of cancer death in relation to scheduled duration of trial treatment for gastrointestinal and non-gastrointestinal cancers. In three large UK trials, long-term post-trial follow-up of individual patients was obtained from death certificates and cancer registries.
Results
In eight eligible trials (25 570 patients, 674 cancer deaths), allocation to aspirin reduced death due to cancer (pooled odds ratio [OR] 0·79, 95% CI 0·68—0·92, p=0·003). On analysis of individual patient data, which were available from seven trials (23 535 patients, 657 cancer deaths), benefit was apparent only after 5 years' follow-up (all cancers, hazard ratio [HR] 0·66, 0·50—0·87; gastrointestinal cancers, 0·46, 0·27—0·77; both p=0·003). The 20-year risk of cancer death (1634 deaths in 12 659 patients in three trials) remained lower in the aspirin groups than in the control groups (all solid cancers, HR 0·80, 0·72—0·88, p<0·0001; gastrointestinal cancers, 0·65, 0·54—0·78, p<0·0001), and benefit increased (interaction p=0·01) with scheduled duration of trial treatment (≥7·5 years: all solid cancers, 0·69, 0·54—0·88, p=0·003; gastrointestinal cancers, 0·41, 0·26—0·66, p=0·0001). The latent period before an effect on deaths was about 5 years for oesophageal, pancreatic, brain, and lung cancer, but was more delayed for stomach, colorectal, and prostate cancer. For lung and oesophageal cancer, benefit was confined to adenocarcinomas, and the overall effect on 20-year risk of cancer death was greatest for adenocarcinomas (HR 0·66, 0·56—0·77, p<0·0001). Benefit was unrelated to aspirin dose (75 mg upwards), sex, or smoking, but increased with age—the absolute reduction in 20-year risk of cancer death reaching 7·08% (2·42—11·74) at age 65 years and older.
Interpretation
Daily aspirin reduced deaths due to several common cancers during and after the trials. Benefit increased with duration of treatment and was consistent across the different study populations. These findings have implications for guidelines on use of aspirin and for understanding of carcinogenesis and its susceptibility to drug intervention.
Funding
None.

[mikesimon]

Hector's post from the second paragraph on was copied from the following link.
http://www.liverdisease.com/painkillers_hepatitis.html

We should always cite the material we copy and paste.

"...Acetylsalicylic acid (aspirin) and other NSAIDs are drugs that are widely used for their anti-inflammatory and analgesic effects. They also have the potential to cause drug-induced liver disease. In fact, many NSAIDs have been withdrawn from the market due to their hepatotoxicity. All NSAIDs have the potential to cause liver injury. However, some NSAIDs are more hepatotoxic than others. NSAIDs presently on the market that have been frequently associated with liver injury are aspirin (ASA), diclofenac (Voltaren), and sulindac (Clinoril). Ibuprofen (Motrin) has been reported to cause severe liver injury in people with hepatitis C. A new generation of NSAIDs, known as the cyclooxygenase-2 (COX-2) inhibitors, has recently been approved by the FDA.  This group of NSAIDs has the advantage of having fewer gastrointestinal side effects – less abdominal discomfort and less risk of gastrointestinal bleeding, than conventional NSAIDs. There are three different COX-2 inhibitors currently available to the public–  Vioxx, Celebrex and Bextra.  COX-2 inhibitors have been associated with some liver dysfunction, although not as commonly as other NSAIDs. Recently, Vioxx has been removed from the market due to heart-related problems. Celebrex and Bextra are currently being investigated for similar heart-related toxicities.

     It is recommended that people with liver disease avoid using all NSAIDs. If NSAIDs are medically required for the treatment of another medical disorder, a reduced dose should be used for a limited period of time and only by people with stable liver disease. Older women with liver disease seem to be particularly susceptible to the hepatotoxicity of NSAIDs and are advised to avoid NSAIDs altogether.  Since NSAIDs may cause salt and water retention people with fluid retention problems such as ascites or leg swelling may suffer worsening of these conditions.  People with decompensated cirrhosis are at increased risk kidney damage stemming from the use of NSAIDs. Since this may lead to hepatorenal syndrome (see Chapter 6), people with advanced liver disease are advised to totally avoid all NSAIDs.  Furthermore, people with ascites (fluid accumulation) may not respond to treatment with water pills (diuretics), while on NSAIDs, as they counteract their actions. ( see chapter 20). People with liver disease who have had internal bleeding, - from an ulcer or esophageal varices, for example, may be at risk for recurrent bleeding induced by NSAIDs, and should totally avoid this class of medications. People who are also taking corticosteroids (such as prednisone), or anticoagulants (such as coumadin) may have and increased risk of complications from NSAIDs.  Finally, people with liver disease who smoke cigarettes or drink alcohol should avoid NSAIDs as they are also at increased risk for its complications...."

[Willy50]

Thanks for the response.  I'm aware that NSAIDS, particularly high dose daily use can be dangerous.  But as with Tylenol....you repeatedly hear that it is safe when taken as directed.  The amounts of aspirin needed to act as a blood thinner are on the order of a half aspirin a day.

I just saw that they were linking aspirin use to lower cancer rate w/ gastro type cancers and wondered what the effect would be in advanced staging and issues that pertain say cirrhosis.  I was aware there could be some negatives and I think it's good to see your article along with the one I posted.  It looks like there could be a lot of negatives.

Your article more than answered my questions and also provided some of the reasons why.

Thanks!!

Willy

[HectorSF]

Aspirin may prevent cancers in other but for persons with HCV and liver disease "the cure" will probably be worse then "the disease". Most people with a high risk of HCC are cirrhotic patients. The aspirin can cause prolonged internal bleeding, cause fluid build up of ascites and edema, rapid deterioration of kidney function and progression of the liver disease. All complications a person with cirrhosis wants to avoid.

Acetylsalicylic acid (aspirin) and other NSAIDs are drugs that are widely used for their anti-inflammatory and analgesic effects. They also have the potential to cause drug-induced liver disease. In fact, many NSAIDs have been withdrawn from the market due to their hepatotoxicity. All NSAIDs have the potential to cause liver injury. However, some NSAIDs are more hepatotoxic than others.

NSAIDs presently on the market that have been frequently associated with liver injury are
aspirin (ASA)
diclofenac (Voltaren)
sulindac (Clinoril)
Ibuprofen (Motrin) has been reported to cause severe liver injury in people with hepatitis C.

A new generation of NSAIDs, known as the cyclooxygenase-2 (COX-2) inhibitors, has recently been approved by the FDA.  This group of NSAIDs has the advantage of having fewer gastrointestinal side effects – less abdominal discomfort and less risk of gastrointestinal bleeding, than conventional NSAIDs. There are three different COX-2 inhibitors currently available to the public–  Vioxx, Celebrex and Bextra.  COX-2 inhibitors have been associated with some liver dysfunction, although not as commonly as other NSAIDs. Recently, Vioxx has been removed from the market due to heart-related problems. Celebrex and Bextra are currently being investigated for similar heart-related toxicities.

It is recommended that people with liver disease avoid using all NSAIDs. If NSAIDs are medically required for the treatment of another medical disorder, a reduced dose should be used for a limited period of time and only by people with stable liver disease. Older women with liver disease seem to be particularly susceptible to the hepatotoxicity of NSAIDs and are advised to avoid NSAIDs altogether.  Since NSAIDs may cause salt and water retention people with fluid retention problems such as ascites or leg swelling may suffer worsening of these conditions.  People with decompensated cirrhosis are at increased risk kidney damage stemming from the use of NSAIDs. Since this may lead to hepatorenal syndrome, people with advanced liver disease are advised to totally avoid all NSAIDs.  Furthermore, people with ascites (fluid accumulation) may not respond to treatment with water pills (diuretics), while on NSAIDs, as they counteract their actions. People with liver disease who have had internal bleeding, - from an ulcer or esophageal varices, for example, may be at risk for recurrent bleeding induced by NSAIDs, and should totally avoid this class of medications. People who are also taking corticosteroids (such as prednisone), or anticoagulants (such as coumadin) may have and increased risk of complications from NSAIDs.  Finally, people with liver disease who smoke cigarettes or drink alcohol should avoid NSAIDs as they are also at increased risk for its complications.

hectorsf