The Lancet and aspirin and all cause mortality

 

There are three papers today in the Lancet about aspirin. I’m going to ignore the two papers about the effect on cancer metastasis, just now, and concentrate on the third, which is titled

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

It’s been covered at the BBC, here. They say that

“Taking a low (75-300mg) daily dose of the drug appeared to cut the total number of cancer cases by about a quarter after only three years – there were nine cancer cases per 1,000 each year in the aspirin-taking group, compared with 12 per 1,000 for those taking dummy pills.

It also reduced the risk of a cancer death by 15% within five years (and sooner if the dose was higher than 300mg)

And if patients stayed on aspirin for longer, their cancer death risk went down even further – by 37% after five years.”

This is the relevant bit from the paper

“Allocation to aspirin reduced cancer deaths (562 vs 664 deaths; odds ratio [OR] 0·85, 95% CI 0·76–0·96, p=0·008; 34 trials, 69 224 participants), particularly from 5 years onwards (92 vs 145; OR 0·63, 95% CI 0·49–0·82, p=0·0005), resulting in fewer non-vascular deaths overall (1021 vs 1173; OR 0·88, 95% CI 0·78–0·96, p=0·003; 51 trials, 77 549 participants). In trials in primary prevention, the reduction in non-vascular deaths accounted for 87 (91%) of 96 deaths prevented. In six trials of daily low-dose aspirin in primary prevention (35 535 participants), aspirin reduced cancer incidence from 3 years onwards (324 vs 421 cases; OR 0·76, 95% CI 0·66–0·88, p=0·0003) in women (132 vs 176; OR 0·75, 95% CI 0·59–0·94, p=0·01) and in men (192 vs245; OR 0·77, 95% CI 0·63–0·93, p=0·008). The reduced risk of major vascular events on aspirin was initially offset by an increased risk of major bleeding, but effects on both outcomes diminished with increasing follow-up, leaving only the reduced risk of cancer (absolute reduction 3·13 [95% CI 1·44–4·82] per 1000 patients per year) from 3 years onwards. Case-fatality from major extracranial bleeds was also lower on aspirin than on control (8/203 vs 15/132; OR 0·32, 95% CI 0·12–0·83, p=0·009).”

 

I have cut and pasted the numbers below. 

It seems that, at 5 years,  1.42% of the the control group had cancers, and 2.94% if the control group. This is a difference, small to an individual, potentially large to a population. But we really need to know about all cause mortality – if all we are doing is reducing cancer incidence by increasing bleeding risk (eg brain haemorrhage) we might not be doing a great deal of good.

This is a very important sentence:

“Allocation to aspirin reduced the risk of non-vascular death in the 51 trials (1021 vs 1173 deaths; OR 0·88, 95% CI 0·78–0·96, p=0·003; 152 deaths avoided in 40 269 participants allocated aspirin; table 1). The proportion of deaths classed as non-vascular varied (heterogeneity p<0·0001), ranging from 10–20% in early, predominantly high-dose trials in patients with ischaemic heart disease to about 70% in predominantly low-dose trials in primary prevention (data not shown). In 12 trials in primary prevention (figure 1), [15][16][17][18],[19][20][21][22][23][24][25] and [26] aspirin reduced non-vascular death (OR 0·88, 95% CI 0·78–0·98, p=0·02; 87 deaths avoided), but not vascular death (OR 0·99, 95% CI 0·87–1·12, nine deaths avoided), such that the effect on all-cause mortality was non-significant (1165 vs 1261 deaths; OR 0·92, 95% CI 0·85–1·00, p=0·06).”

Repeat: the effect on all cause mortality was not significant.

I think we need to discuss this better – rather a lot of people need to be treated with aspirin to prevent cancer, and we don’t know that this will reduce overall death rates.

I need to read the other two papers, but busy day today.

 

 

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