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Effect of daily aspirin on long-term risk of death due to cancer: analysis of individual patient data from randomised trials.
Lancet. 2011 Jan 1; 377(9759):31-41
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05 Jan 2011
DOI: 10.3410/f.7275961.7518067
This article is excellent because it shows the potential benefits of aspirin in cancer prevention.
The main finding in section two is that long-term aspirin therapy may decrease cancer incidence. This study does challenge accepted endpoints but furthermore does provide a small amount of evidence...Continue reading
The main finding in section two is that long-term aspirin therapy may decrease cancer incidence. This study does challenge accepted endpoints but furthermore does provide a small amount of evidence...Continue reading
This article is excellent because it shows the potential benefits of aspirin in cancer prevention.
The main finding in section two is that long-term aspirin therapy may decrease cancer incidence. This study does challenge accepted endpoints but furthermore does provide a small amount of evidence to show that aspirin in a randomized control trial needs to be tested.
The drawback of the study would be that the data collection on the risks of low-dose aspirin is not clear, particularly gastrointestinal (GI) hemorrhage, and this does need a randomized trial such as the "Aspirin Esomeprazole Chemoprevention Trial" (AspECT) to access these clearly (see ISRCTN85156844 and {1} on which I am author).
The main finding in section two is that long-term aspirin therapy may decrease cancer incidence. This study does challenge accepted endpoints but furthermore does provide a small amount of evidence to show that aspirin in a randomized control trial needs to be tested.
The drawback of the study would be that the data collection on the risks of low-dose aspirin is not clear, particularly gastrointestinal (GI) hemorrhage, and this does need a randomized trial such as the "Aspirin Esomeprazole Chemoprevention Trial" (AspECT) to access these clearly (see ISRCTN85156844 and {1} on which I am author).
References
Disclosures
None declared
Add Comment
Jankowski J: F1000Prime Recommendation of [Rothwell PM et al., Lancet 2011, 377(9759):31-41]. In F1000Prime, 05 Jan 2011; DOI: 10.3410/f.7275961.7518067. F1000Prime.com/7275961#eval7518067
14 Feb 2011
Pagona Lagiou
F1000 Public Health & Epidemiology
University of Athens Medical School, Athens, Greece.
F1000 Public Health & Epidemiology
University of Athens Medical School, Athens, Greece.
DOI: 10.3410/f.7275961.8695054
This study provides the strongest evidence yet that long-term intake of low-dose aspirin may convey substantial protection against risk of death from cancer.
In a pooled analysis of data from eight randomized trials comprising 25,570 patients, 674 of whom died from cancer, the authors report that lterm...Continue reading
In a pooled analysis of data from eight randomized trials comprising 25,570 patients, 674 of whom died from cancer, the authors report that lterm...Continue reading
This study provides the strongest evidence yet that long-term intake of low-dose aspirin may convey substantial protection against risk of death from cancer.
In a pooled analysis of data from eight randomized trials comprising 25,570 patients, 674 of whom died from cancer, the authors report that long-term daily intake of aspirin, even at doses as low as 75-100mg per day, was associated with a 21% reduction in cancer mortality. Higher daily doses up to 1200mg did not convey any additional protection. The association was evident after the first 5 years of follow up. It should be stressed that too few women in the study had long-term follow-up. In line with previous evidence, most of the reduction was with respect to colorectal cancer, but it was also apparent for cancers of the esophagus, stomach and, somewhat unexpectedly, lung cancer. Regarding histological types, the inverse association was stronger for adenocarcinomas. The results of the study point to an important weapon against cancer, the gains from which should be carefully weighed against the risks of gastrointestinal bleeding.
In a pooled analysis of data from eight randomized trials comprising 25,570 patients, 674 of whom died from cancer, the authors report that long-term daily intake of aspirin, even at doses as low as 75-100mg per day, was associated with a 21% reduction in cancer mortality. Higher daily doses up to 1200mg did not convey any additional protection. The association was evident after the first 5 years of follow up. It should be stressed that too few women in the study had long-term follow-up. In line with previous evidence, most of the reduction was with respect to colorectal cancer, but it was also apparent for cancers of the esophagus, stomach and, somewhat unexpectedly, lung cancer. Regarding histological types, the inverse association was stronger for adenocarcinomas. The results of the study point to an important weapon against cancer, the gains from which should be carefully weighed against the risks of gastrointestinal bleeding.
Disclosures
None declared
Lagiou P: F1000Prime Recommendation of [Rothwell PM et al., Lancet 2011, 377(9759):31-41]. In F1000Prime, 14 Feb 2011; DOI: 10.3410/f.7275961.8695054. F1000Prime.com/7275961#eval8695054
22 Mar 2011
DOI: 10.3410/f.7275961.9761054
This is an interesting meta-analysis in which the authors attempted to answer the question of whether daily aspirin would reduce the risk of deaths due to cancer. Because of a paucity of primary trial data which examine this question, the authors, instead, used data from clinical trials initially designed...Continue reading
This is an interesting meta-analysis in which the authors attempted to answer the question of whether daily aspirin would reduce the risk of deaths due to cancer. Because of a paucity of primary trial data which examine this question, the authors, instead, used data from clinical trials initially designed to look at the effect of aspirin in vascular disease.
Besides showing a reduction in the number of deaths from solid tumor cancers and the potential changes to primary care practice, this is an important article because of the authors’ methodology. Although study-level meta-analyses have become common in most medical journals, less frequently seen are meta-analyses that incorporate patient-level information. Even more unusual is the authors’ use of data from clinical trials initially designed to find outcomes unrelated to those examined in this meta-analysis.
In this meta-analysis of eight clinical trials, with a total enrolment of greater than 14,000 patients, the authors demonstrated a 0.21 relative risk reduction in the number of cancer-related deaths during the course of the trials. In the long-term follow-up, using data from three of the trials, the authors show that this effect persisted out to 20 years (relative risk reduction of 0.2 for all solid cancers and 0.35 for gastrointestinal cancers). Most of this benefit was delayed, with a more significant reduction beginning five years after the start of treatment. While there was not a dose-related effect, there was an increased benefit based on the length of treatment.
These same authors have demonstrated in previous studies a benefit of aspirin in preventing colorectal cancers {1,2}, though the results for other cancers have thus far been less promising {3,4}. Potential mechanisms have been shown in animal studies {5,6,7}, but the applicability of these to humans is unknown. To our knowledge, this is one of the first studies to demonstrate that aspirin reduces incidence for non-gastrointestinal cancers.
While the effect on cancer deaths was significant and durable out to 20 years, there are some limitations based on the study design. The majority of patients in this study were men, with this gender disparity being more pronounced in the three trials used for long-term follow-up. Again, subjects were initially enrolled in studies to evaluate the effect of aspirin on vascular disease and, thus, it is difficult to extrapolate these findings to other groups. Furthermore, since the original trial participants were enrolled for vascular disease studies, by current practice most already had an indication for aspirin therapy. Finally, there is no comment on possible increased bleeding complications from aspirin therapy.
Nevertheless, this study suggests that daily aspirin therapy may reduce the risk of cancer-related deaths, particularly those of gastrointestinal origin. These results may provide further reason for a primary care provider to start patients on aspirin therapy, which would already be recommended by current guidelines; these results may also provide further motivation to patients to start aspirin therapy for other clinical indications. However, caution and further study would be recommended before primary care providers change their clinical practice patterns to start recommending aspirin for primary cancer prevention. At present, we do not yet recommend aspirin in patients without other clinical indications for this drug; while the authors examined total and cancer-related mortality, the absence of information related to gastrointestinal bleeding or chronic kidney injury risk somewhat dampens our enthusiasm for aspirin as a primary prevention strategy.
Besides showing a reduction in the number of deaths from solid tumor cancers and the potential changes to primary care practice, this is an important article because of the authors’ methodology. Although study-level meta-analyses have become common in most medical journals, less frequently seen are meta-analyses that incorporate patient-level information. Even more unusual is the authors’ use of data from clinical trials initially designed to find outcomes unrelated to those examined in this meta-analysis.
In this meta-analysis of eight clinical trials, with a total enrolment of greater than 14,000 patients, the authors demonstrated a 0.21 relative risk reduction in the number of cancer-related deaths during the course of the trials. In the long-term follow-up, using data from three of the trials, the authors show that this effect persisted out to 20 years (relative risk reduction of 0.2 for all solid cancers and 0.35 for gastrointestinal cancers). Most of this benefit was delayed, with a more significant reduction beginning five years after the start of treatment. While there was not a dose-related effect, there was an increased benefit based on the length of treatment.
These same authors have demonstrated in previous studies a benefit of aspirin in preventing colorectal cancers {1,2}, though the results for other cancers have thus far been less promising {3,4}. Potential mechanisms have been shown in animal studies {5,6,7}, but the applicability of these to humans is unknown. To our knowledge, this is one of the first studies to demonstrate that aspirin reduces incidence for non-gastrointestinal cancers.
While the effect on cancer deaths was significant and durable out to 20 years, there are some limitations based on the study design. The majority of patients in this study were men, with this gender disparity being more pronounced in the three trials used for long-term follow-up. Again, subjects were initially enrolled in studies to evaluate the effect of aspirin on vascular disease and, thus, it is difficult to extrapolate these findings to other groups. Furthermore, since the original trial participants were enrolled for vascular disease studies, by current practice most already had an indication for aspirin therapy. Finally, there is no comment on possible increased bleeding complications from aspirin therapy.
Nevertheless, this study suggests that daily aspirin therapy may reduce the risk of cancer-related deaths, particularly those of gastrointestinal origin. These results may provide further reason for a primary care provider to start patients on aspirin therapy, which would already be recommended by current guidelines; these results may also provide further motivation to patients to start aspirin therapy for other clinical indications. However, caution and further study would be recommended before primary care providers change their clinical practice patterns to start recommending aspirin for primary cancer prevention. At present, we do not yet recommend aspirin in patients without other clinical indications for this drug; while the authors examined total and cancer-related mortality, the absence of information related to gastrointestinal bleeding or chronic kidney injury risk somewhat dampens our enthusiasm for aspirin as a primary prevention strategy.
References
1.
Effect of aspirin on long-term risk of colorectal cancer: consistent evidence from randomised and observational studies.
Lancet 2007 May 12; 9573(369):1603-13
PMID: 17499602
2.
Long-term effect of aspirin on colorectal cancer incidence and mortality: 20-year follow-up of five randomised trials.
Lancet 2010 Nov 20; 9754(376):1741-50
PMID: 20970847
3.
Aspirin and cancer risk: a summary review to 2007.
Recent Results Cancer Res 2009; (181):231-51
PMID: 19213573
4.
Low-dose aspirin in the primary prevention of cancer: the Women's Health Study: a randomized controlled trial.
JAMA 2005 Jul 6; 1(294):47-55
PMID: 15998890
5.
“Cox-2: A New Target for Cancer Prevention and Treatment: 37 (Progress in Experimental Tumour Research)” Dubois RN and Dannenberg AJ (eds) New York: S Karger AG, 2003 [ISBN:978-3805575362].
6.
Aspirin, salicylates, and cancer.
Lancet 2009 Apr 11; 9671(373):1301-9
PMID: 19328542
7.
Nonsteroidal anti-inflammatory drugs as anticancer agents: mechanistic, pharmacologic, and clinical issues.
J Natl Cancer Inst 2002 Feb 20; 4(94):252-66
PMID: 11854387
Acknowledgments
I would like to thank Zachary Boss and Melissa Hagman for their assistance in the evaluation of this article.
Disclosures
None declared
Choe J: F1000Prime Recommendation of [Rothwell PM et al., Lancet 2011, 377(9759):31-41]. In F1000Prime, 22 Mar 2011; DOI: 10.3410/f.7275961.9761054. F1000Prime.com/7275961#eval9761054
F1000Prime Recommendations, Dissents and Comments for [Rothwell PM et al., Lancet 2011, 377(9759):31-41]. In F1000Prime, 19 Jun 2013; F1000Prime.com/7275961
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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.
Copyright © 2011 Elsevier Ltd. All rights reserved.
DOI: 10.1016/S0140-6736(10)62110-1
PMID: 21144578
