Risks and Benefits of Aspirin

reposted from: http://www.thelancet.com/journals/lancet/article/PIIS0140-6736(10)62110-1/fulltext

crabsallover highlights, key points, comments / links.

Results

Figure 1: In eight eligible trials (25570 patients, 674 cancer deaths): 327 deaths due to cancer occurred with patients treated with aspirin out of 14035 in the 8 trials. 347 deaths due to cancer occurred with control patients out of 11535 in the 8 trials.

With Aspirin: 327/14035 = 2.33% died of cancer

With Control: 347/11535 = 3.01% died of cancer

Over about 6 years 0.68% fewer died of cancer because they took a daily Aspirin.

Reclassification of cause of death in a small number of cases in UK-TIA and TPT had little effect on the pooled estimate (686 (684 in figures below) deaths; OR 0·80, 0·69—0·93, p=0·004, webappendix p 3).

Results

Web-Figure 1: In eight eligible trials 335 deaths due to cancer occurred with patients treated with aspirin out of 14035 in the 8 trials. 351 deaths due to cancer occurred with control patients out of 11535 in the 8 trials.

With Aspirin: 333/14035 = 2.37% died of cancer

With Control: 351/11535 = 3.04% died of cancer

So over about 6 years 0.67% fewer died of cancer because they took a daily Aspirin. The number needed to treat with Aspirin over 6 years to prevent one death is 149 (100%/0.67%).

A relative 22% reduction of death with Aspirin ((3.04-2.37)/3.04)

In 3 of the trials (TPT, UK-TIA, BDAT) 1634 (in the 3 trials 740, 287, 607) died of cancer over 20 years follow-up out of 11845 (2545/2540, 806/815, 3429/1710)

13.79% died of cancer in 3 trials over 20 years (1634 died out of 11845 trialists). Assuming a 22% relative reduction of 13.79%, 10.75% taking aspirin would die over 20 years, a difference of 3.04%

Using Spinning the Disk at UnderstandingCertainty.org http://understandinguncertainty.org/spinning input deaths.

or more optimistically 

The Number needed to treat: 33 (100%/3.04%)

Aspirin reduces cancer but it also reduces risk of heart attacks and strokes. However Aspirin increases risk of death from fatal bleeds (brain haemorrhages, fatal stomach ulcers etc).

The all-cause mortality, which includes fatal bleeds is stated by Peter Rothwell:-

'The reduction in cancer deaths on aspirin during the trials resulted in lowered in-trial all-cause mortality (10·2% vs 11·1%, OR 0·92, 0·85—1·00, p=0·047, webappendix p 4)' 

Peter Rothwell on 14th personally communicated with crabsallover when I asked' 

... Can you let me know how you arrived at the 10% all-cause mortality figure when taking aspirin daily? 

Peter Rothwell said

The estimate was based on the observed effect in the 8 RCTs. The OR for all cause mortality in the trials was 0.92 (see paper). Excluding patients who were randomised but stopped treatment before the first follow-up it was 0.88 in those trials with the data available. So "about 10%" seemed reasonable. However, we are in the process of doing a formal health economics paper, which I will send you in due course. The estimate of effect of all-cause mortality that we published (OR=0.92) could well be an underestimate because after exclusion of patients who were non-compliant (so-called "on-treatment analysis") the effect was larger (OR=0.88) (unpublished data).  

All Cause Mortality:

1432/14035 (aspirin) =10.2% v 1275 /11535 =11.1% (control)

Need to treat 111 (1000/(111-102)) people to save one person 

In order to save one person from all-cause mortality we need to treat 111 people with daily 75mg aspirin. If a million people took aspirin (about 8% of the UK 15M population between 45-70 years) 9,000 (1,000,000/111) would not die. If everyone between these ages took aspirin 135,000 (15M/111) would not die.

Aspirin reduces your chance of experiencing All-Cause mortality by 8%

All-cause mortality is reduced with Aspirin

Fergus Walsh & Crabsallover talks to Peter Rothwell on aspirin & cancer prevention

reposted from: BBC interview by Fergus Walsh with Peter Rothwell





Full Transcription by crabsallover
0-0.26': Peter Rothwell: What we found was that in the trials where people had taken aspirin for 4, 5, 6 or 7 years on average, the risk of dying of cancer was reduced by about 25% during that time. The risk of dying from any cause was reduced by about 10%. What we then found was when we followed up these trials, the risk of dying of cancer over the next 20 years was reduced by about 20%.
0.27-0.31': Fergus Walsh: Why do you think aspirin has this protective effect?
0.32- 1.17': Peter Rothwell: There has been a lot of work over the years looking at tumour cells & animals with tumours which seems to suggest that aspirin affects the very early development of cancer cells. The fundamental  property of cancer cells is that they cease to respond to the normal signals that control growth and they grow uncontrollably. What aspirin does is that it reduces that rate of growth and seems to encourage cells to actually do the opposite. When they develop mutations, it encourages something called  apoptosis which is essentially suicide of the cell, the cell realises as it were that it has a problem and it self destructs. And there are mechanisms that leads cells to do that and aspirin appears to encourage those mechanisms.
1.18'- 1.36': Fergus Walsh: Lots of people take aspirin to guard against heart attack and stroke, if you add in the effect of cancer does this now mean that generally speaking it would be wise for middle aged people to take aspirin.
1.37'-2.17': Peter Rothwell: I think at the moment as you say, if you set aside the cancer results first of all the balance of risk and benefit is relatively fine in people who don't have risk factors for heart attacks and stroke. But if add on the cancer benefit it certainly pushes things in the direction of taking aspirin. If you have risk factors for heart attacks and strokes as well, the guidelines currently say you should probably think about taking aspirin anyway in your late forties or fifties particularly if you a man. And I think the cancer effects now certainly make that much more worthwhile. 
2.18'- 2.19': Fergus Walsh: But there are side affects and they can be serious?
2.20'-2.55': Peter Rothwell: They can. Their is a risk bleeding, of major bleeding of 1 per 1000 years for each patient as it were OR 1 per 1000 patient years OR 1 bleed per 1000 patients per year. Only a small proportion about 5% of those bleeds are fatal, so it's a small risk of death. When you put together all the risks, the risk of bleeding, the risk of heart attack and stroke and the effect on cancer, from the trials we looked at, taking aspirin reduces the risk  of premature death by about 10%.


Crabsallover Notes: in Peter Rothwell et al Lancet paper (pg 9) they say "Our analyses show that taking aspirin daily for 5–10 years would reduce all-cause mortality (including any fatal bleeds) during that time by about 10% (relative risk reduction)." 


In a personal communication  on 14th December, I emailed Peter Rothwell:-

'Dear Prof. Peter Rothwell,

In your December 2010 Lancet paper (pg 9) http://www.thelancet.com/journals/lancet/article/PIIS0140-6736(10)62110-1/abstract you say  "Our analyses show that taking aspirin daily for 5–10 years would reduce all-cause mortality (including any fatal bleeds) during that time by about 10% (relative risk reduction)." 

Can you let me know how you arrived at the 10% all-cause mortality figure when taking aspirin daily? What were the individual % components of increased risk from serious gastrointestinal bleed, Gastric/duodenal ulcer, Occlusive & Haemorrhagic stroke (ref: Cuzick et al, Lancet Oncol 2009; 10: 501–07, table 2) and  reduced risk of cancer, heart attacks and other strokes?'

The same day Peter Rothwell replied "The estimate was based on the observed effect in the 8 RCTs. The Odds Ratio (OR) for all-cause mortality in the trials was 0.92 (see paper). Excluding patients who were randomised but stopped treatment before the first follow-up it was 0.88 in those trials with the data available. So "about 10%" seemed reasonable. However, we are in the process of doing a formal health economics paper, which I will send you in due course."

A small daily dose of aspirin - 75mg - substantially reduces death rates from a range of common cancers, a study suggests.

Research at Oxford University and other centres found that it cut overall cancer deaths by at least a fifth.

The study, published in the Lancet, covered some 25,000 patients, mostly from the UK.

Experts say the findings show aspirin's benefits often outweighed its associated risk of causing bleeding.

Aspirin is already known to cut the risk of heart attack and stroke among those at increased risk. But the protective effects against cardiovascular disease are thought to be small for healthy adults, and aspirin increases the risks of stomach and gut bleeds.

However, this latest research shows that when weighing up the risks and benefits of taking aspirin, experts should also consider its protective effect against cancer.

Those patients who were given aspirin had a 25% lower risk of death from cancer during the trial period and a 10% reduction in death from any cause compared to patients who were not given the drug.

Lasting protection

The treatment with aspirin lasted for between four and eight years, but long term-follow-up of around 12,500 patients showed the protective effect continued for 20 years in both men and women.

Continue reading the main story

“Start Quote

We encourage anyone interested in taking aspirin on a regular basis to talk to their GP first”

Ed YoungCancer Research UK

Lead researcher Professor Peter Rothwell said the findings might well underestimate the reduction in deaths that would result from longer-term treatment with aspirin.

The risk of cancer death was reduced by 20% over 20 years. For individual cancers the reduction was about 40% for bowel cancer, 30% for lung cancer, 10% for prostate cancer and 60% for oesophageal cancer.

The reductions in pancreas, stomach and brain cancers were difficult to quantify because of smaller numbers of deaths.

There was also not enough data to show an effect on breast or ovarian cancer and the authors suggest this is because there were not enough women in the trials. Large-scale studies investigating the effects on these cancers are under way.

Professor Rothwell said he was not urging healthy middle-aged adults to immediately start taking aspirin, but said the evidence on cancer "tips things towards it being well worth it". The benefit in cancer reduction were found from a low daily dose of 75mg.

Professor Rothwell said the annual risk of major internal bleeding was about 1 in 1,000 and aspirin roughly doubled that risk. But he said the danger of major bleeding was "very low" in middle age but increased dramatically after 75.

Continue reading the main story

“Start Quote

Aspirin should be thought of in the same context as lifestyle changes such as diet and exercise which can help to preserve health”

Professor Peter ElwoodCardiff University

• Aspirin: a personal choice for all

A sensible time to consider starting daily aspirin use would be between 45-50, continuing for around 25 years, he said.

Cancer Research UK described the results as "promising". But Ed Yong, head of health information and evidence, said: "We encourage anyone interested in taking aspirin on a regular basis to talk to their GP first."

Professor Peter Elwood, an epidemiologist from Cardiff University, who carried out some of the first studies into the effects of aspirin on health, said individuals should make up their own minds:

"Aspirin should be thought of in the same context as lifestyle changes such as diet and exercise which can help to preserve health."

Professor Elwood said taking aspirin at night and with calcium seemed to enhance its effects. He suggested taking it with a glass of milk as this could also reduce stomach irritation.

More on This Story

Related stories

• Aspirin: a personal decision 07 DECEMBER 2010, HEALTH
• Aspirin: What are pros and cons? 07 DECEMBER 2010, HEALTH
• Aspirin 'cuts bowel cancer cases' 21 OCTOBER 2010, HEALTH

Related Internet links

• The Lancet paper