Wednesday, 15 December 2010

"3900 lives saved OR 2850 lives lost each year in UK by daily aspirin" says crabsallover

Cancer Research UK (ref: 8) has commented on Peter Rothwell and colleagues Lancet published research (ref: 5) on effect of daily aspirin on cancer levels and all cause risks: in para 4 CancerResearchUK say "The results showed that people who took at least 75 milligrams of aspirin (the same dose as in a ‘junior’ aspirin) every day had around a 20 per cent lower risk of dying from cancer. To put this into perspective, if 100,000 people take aspirin every day for at least five years, around 56 cancer deaths will be avoided."

How did Cancer Research UK come up with 56 per 100,000 figure? I calculated 51 per 100,000:-

1) 1 in 4 (26%) of all deaths in UK are from cancer
2) 153,491 in UK in 2005 died of cancer
3) UK Population in mid 2006 was 60,587,300
4) from 2) & 3) 253 per 100,000 died of cancer (100,000 x 153,491/60,587,300)
5) 20% of 253 is 51 persons per 100,000 who don't die due to cancer because they take daily aspirin.(20 x 253/100)
6) a 10% all-cause death reduction (refs: (5) & (6)) means 25 persons per 100,000 will not die because they take daily aspirin.(10 x 253/100)

Peter Rothwell all-cause mortality from taking Aspirin
Peter Rothwell  (ref: 2) says that all-cause mortality risk from the 8 trials studied (ref: 5) was estimated at 10% when taking 75mg per day aspirin. This is the net benefit taking into account the risks of death from bleeding or stroke plus benefits of reduced cancer, heart attack and stroke.

In a personal communication (ref: 6) with crabsallover on 14th December 2010 Prof. Peter Rothwell says 'The estimate was based on the observed effect in the 8 Randomly Controlled Trials. 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.'

So I calculate, as a result of taking a daily junior 75mg aspirin, about 51 per 100,000 will not die of cancer/heart attack/stroke but 25 per 100,000 will die of bleeding or a stroke caused by aspirin giving a net 26 lives per 100,000 saved by taking aspirin.

UK Population between ages of 45-70 years
From UK population stats, I estimate that there are about 15M people in the 45-70 year age group (25yrs x 600,000 people).

Crabsallover Conclusion of Aspirin benefit/risks based on Peter Rothwell research
The evidence of Peter Rothwell et al (ref: 5) is that the net benefit of taking daily 75mg asprin is a 10% reduction in all-cause death. I have calculated that a net 26 lives (51 lives saved due to effect of aspirin in reducing cancer/heart attacks/strokes less 25 lives lost due to aspirin causing fatal stomach bleeding & ulcers and strokes) will be saved for every 100,000 people who take aspirin daily (commencing at 45/50 years years, ending at 70 years). I calculate that if all 15 million UK people in the 45-70 year age bracket took a daily aspirin, 3900 lives (26 x 15M/100,000) would be saved each year.

Jack Cuzick et - Risks of Aspirin
Jack Cuzick (ref: 1) rates the risk of aspirin 3 times higher than Peter Rothwell. Cuzick estimates 75 deaths per 100,000 arising from bleeding, occlusive & haemorrhhagic stroke and ulcers (cf Peter Rothwell estimates 25 death per 100,000 taking aspirin).

How many will die because they take aspirin according to Jack Cuzick? I have calculated that:-
  • About 100 per 100,000 per annum (0.1%) will have a Serious gastrointestinal bleed per year (ref: 1)  and of these bleeding events 5% are fatal ie. 5 per 100,000 (ref: 2). 
  • 300 (0.3%) per 100,000 pa will have an Occlusive stroke (a stroke caused by a blood clot) 
  • 40 (0.04%) per 100,000 will have a Haemorrhagic stroke (a stroke caused by the rupture of a blood vessel in the brain) (ref: 1). 
    • If 20% of those who have a Occlusive & Haemorrhagic stroke die (ref: 3) then 68 per 100,000 pa will die
  • In the United States about 4 million people have active peptic ulcers and about 350,000 new cases are diagnosed each year. Four times as many duodenal ulcers (ie. 1.4M) as gastric ulcers are diagnosed. (ref: 4) Approximately 3,000 deaths per year in the United States are due to duodenal ulcer and 3,000 to gastric ulcer. (ref: 7)
    • 6000 deaths from 350,000 peptic ulcers + 1.4M gastric ulcers = 6000/1.75M= 0.3% fatality rate (ref: 4)
  • A further 600 (0.6%) per 100,000 will have gastric/duodenal ulcers. (ref: 1) 
    • Of the 600 cases of ulcers only 0.3% will be fatal. ie 600 * 0.3% = 2 per 100,000  
Total: 5 (bleeding) + 68 (stroke) + 2 (ulcer) = 75 per 100,000 will die because they have taken aspirin but only 56 (Peter Rothwell ref: 5) will be saved from dying from cancer. Hence the net effect might be 19 extra deaths per 100,000 taking daily aspirin. From UK population stats, I estimate that there are about 15M people in the 45-70 year age group (25yrs x 600,000 people). I calculate 2850 net lives (15,000,000/100,000 x 19) could be lost by taking daily aspirin according to Jack Cuzick figures.

"3900 lives saved OR 2850 lives lost each year in UK by daily aspirin" says crabsallover

So which is the most likely net benefit or risk of taking daily aspirin? Either 26 lives per 100,000 or 3900 saved using Peter Rothwell's research or 19 per 100,000 or 2850 lives lost if Jack Cuzick's research is more correct.

What assumptions have I made that are not correct?

(1): Lancet Oncol 2009; 10: 501–07 - Jack Cuzick et al.
(2): Peter Rothwell interviewed by the BBCs Fergus Walsh 
(3):;28/11/2180 (Note 1)
(5): Peter Rothwell et al, The Lancet, 7th December 2010
(6): Personal Communication between Peter Rothwell and Crabsallover, 14th December 2010
(8): Cancer Research UK blog

Note 1: weighted average fatalities from stroke

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