Aspirin in the prevention of cancer

Abstract

Peter Rothwell and colleagues, in their meta-analysis of randomised trials (Jan 1, p 31),1Rothwell PM Fowkes FG Belch JF Ogawa H Warlow CP Meade TW Effect of daily aspirin on long-term risk of death due to cancer: analysis of individual patient data from randomised trials.Lancet. 2011; 377: 31-41Summary Full Text Full Text PDF PubMed Scopus (1184) Google Scholar show that low-dose long-term aspirin use reduces the risk of several cancers. Before this information was available, the balance of benefit and harm in taking aspirin in the primary prevention of coronary heart disease and stroke (cardiovascular disease [CVD]) was uncertain. The new data on cancer help to clarify the net benefit of aspirin, particularly if aspirin were included with a statin and blood-pressure-lowering drugs in a combined formulation (Polypill).The table shows the estimated number of first CVD events and cancer deaths prevented in England and Wales in 1 year on the basis of a Polypill (composed of three blood-pressure-lowering drugs at half standard dose and a statin at standard dose such as simvastatin 40 mg), with or without aspirin. In people aged 55–89 years, for example, 186 000 CVD events and cancer deaths would be prevented. The table shows that 120 such outcomes would be prevented in 1000 people over a period of 20 years (or 170 per 1000 over 35 years).2Law M Wald N Morris J Lowering blood pressure to prevent myocardial infarction and stroke: a new preventive strategy.Health Technol Assess. 2003; 7: 31Crossref Scopus (225) Google Scholar, 3Office for National StatisticsMortality statistics: deaths registered in 2009. Stationery Office, London2010http://www.statistics.gov.uk/downloads/theme_health/dr2009/dr-09.pdfGoogle Scholar, 4Antithrombotic Trialists' (ATT) CollaborationAspirin in the primary and secondary prevention of vascular disease: collaborative meta-analysis of individual participant data from randomised trials.Lancet. 2009; 373: 1849-1860Summary Full Text Full Text PDF PubMed Scopus (2739) Google Scholar, 5Law MR Wald NJ Rudnicka AR Quantifying the effect of statins on low density lipoprotein cholesterol, ischaemic heart disease, and stroke: systematic review and meta-analysis.BMJ. 2003; 326: 1423-1427Crossref PubMed Google Scholar, 6Wald NJ Law MR A strategy to reduce cardiovascular disease by more than 80%.BMJ. 2003; 326: 1419-1423Crossref PubMed Google ScholarTableEstimated number of cardiovascular disease (CVD) events and cancer deaths prevented in England and Wales in 1 year according to Polypill use, with and without aspirin, number of such events prevented in 1000 people aged 55 years over periods of 20 years and 35 years, and corresponding number of asprin-induced major extracranial bleedsPolypill including aspirinPolypill excluding aspirinAspirin aloneEffect of adding aspirin to polypillNumber of CVD events and cancer deaths prevented*Rounded to the nearest 1000 and nearest 10.Among people aged 55–74 years in 1 year80 00060 00030 00020 000Among people aged 55–89 years in 1 year186 000141 00068 00045 000Among 1000 people aged 55 years over 20 years120904030Among 1000 people aged 55 years over 35 years1701205050Number of aspirin-induced major extracranial bleedsAmong 1000 people aged 55 years over 20 years6055Among 1000 people aged 55 years over 35 years8088CVD incidence rates taken from reference 2Law M Wald N Morris J Lowering blood pressure to prevent myocardial infarction and stroke: a new preventive strategy.Health Technol Assess. 2003; 7: 31Crossref Scopus (225) Google Scholar (assuming 10% of strokes occur in people who have already had an ischaemic heart disease [IHD] event and vice versa); cancer mortality rates taken from reference 3Office for National StatisticsMortality statistics: deaths registered in 2009. Stationery Office, London2010http://www.statistics.gov.uk/downloads/theme_health/dr2009/dr-09.pdfGoogle Scholar. Relative risks associated with aspirin: IHD 0·77,4Antithrombotic Trialists' (ATT) CollaborationAspirin in the primary and secondary prevention of vascular disease: collaborative meta-analysis of individual participant data from randomised trials.Lancet. 2009; 373: 1849-1860Summary Full Text Full Text PDF PubMed Scopus (2739) Google Scholar stroke 0·95,4Antithrombotic Trialists' (ATT) CollaborationAspirin in the primary and secondary prevention of vascular disease: collaborative meta-analysis of individual participant data from randomised trials.Lancet. 2009; 373: 1849-1860Summary Full Text Full Text PDF PubMed Scopus (2739) Google Scholar cancer (after 5 years of use) 0·66.5Law MR Wald NJ Rudnicka AR Quantifying the effect of statins on low density lipoprotein cholesterol, ischaemic heart disease, and stroke: systematic review and meta-analysis.BMJ. 2003; 326: 1423-1427Crossref PubMed Google Scholar Relative risks associated with statins: IHD (only after 3 years of use) 0·39,5Law MR Wald NJ Rudnicka AR Quantifying the effect of statins on low density lipoprotein cholesterol, ischaemic heart disease, and stroke: systematic review and meta-analysis.BMJ. 2003; 326: 1423-1427Crossref PubMed Google Scholar stroke 0·87,5Law MR Wald NJ Rudnicka AR Quantifying the effect of statins on low density lipoprotein cholesterol, ischaemic heart disease, and stroke: systematic review and meta-analysis.BMJ. 2003; 326: 1423-1427Crossref PubMed Google Scholar cancer 1·00. Relative risks associated with three blood-pressure-lowering agents: IHD 0·64,6Wald NJ Law MR A strategy to reduce cardiovascular disease by more than 80%.BMJ. 2003; 326: 1419-1423Crossref PubMed Google Scholar stroke 0·37,6Wald NJ Law MR A strategy to reduce cardiovascular disease by more than 80%.BMJ. 2003; 326: 1419-1423Crossref PubMed Google Scholar cancer 1·00. Aspirin-induced major extracranial bleeds=three per 10 000 per year.4Antithrombotic Trialists' (ATT) CollaborationAspirin in the primary and secondary prevention of vascular disease: collaborative meta-analysis of individual participant data from randomised trials.Lancet. 2009; 373: 1849-1860Summary Full Text Full Text PDF PubMed Scopus (2739) Google Scholar* Rounded to the nearest 1000 and nearest 10. Open table in a new tab Aspirin causes substantially fewer major extracranial bleeds that require a blood transfusion than the number of CVD events and cancer deaths prevented (table). However, the risk of an aspirin-induced major extracranial bleed increases with age.4Antithrombotic Trialists' (ATT) CollaborationAspirin in the primary and secondary prevention of vascular disease: collaborative meta-analysis of individual participant data from randomised trials.Lancet. 2009; 373: 1849-1860Summary Full Text Full Text PDF PubMed Scopus (2739) Google Scholar The estimates for such bleeds shown in the table among people aged 55 years over a period of 20 years are based on observed data and are likely to be accurate, but the numbers in people older than 75 years are uncertain—they would be twice those shown if the age trend to 75 years continues to 90 years.Given the results published by Rothwell and colleagues,1Rothwell PM Fowkes FG Belch JF Ogawa H Warlow CP Meade TW Effect of daily aspirin on long-term risk of death due to cancer: analysis of individual patient data from randomised trials.Lancet. 2011; 377: 31-41Summary Full Text Full Text PDF PubMed Scopus (1184) Google Scholar the balance of the evidence is in favour of including aspirin in a Polypill strategy to prevent CVD and cancer.NW and ML hold a European and Canadian patent (pending in the USA) for the Polypill, filed in April 2000. Peter Rothwell and colleagues, in their meta-analysis of randomised trials (Jan 1, p 31),1Rothwell PM Fowkes FG Belch JF Ogawa H Warlow CP Meade TW Effect of daily aspirin on long-term risk of death due to cancer: analysis of individual patient data from randomised trials.Lancet. 2011; 377: 31-41Summary Full Text Full Text PDF PubMed Scopus (1184) Google Scholar show that low-dose long-term aspirin use reduces the risk of several cancers. Before this information was available, the balance of benefit and harm in taking aspirin in the primary prevention of coronary heart disease and stroke (cardiovascular disease [CVD]) was uncertain. The new data on cancer help to clarify the net benefit of aspirin, particularly if aspirin were included with a statin and blood-pressure-lowering drugs in a combined formulation (Polypill). The table shows the estimated number of first CVD events and cancer deaths prevented in England and Wales in 1 year on the basis of a Polypill (composed of three blood-pressure-lowering drugs at half standard dose and a statin at standard dose such as simvastatin 40 mg), with or without aspirin. In people aged 55–89 years, for example, 186 000 CVD events and cancer deaths would be prevented. The table shows that 120 such outcomes would be prevented in 1000 people over a period of 20 years (or 170 per 1000 over 35 years).2Law M Wald N Morris J Lowering blood pressure to prevent myocardial infarction and stroke: a new preventive strategy.Health Technol Assess. 2003; 7: 31Crossref Scopus (225) Google Scholar, 3Office for National StatisticsMortality statistics: deaths registered in 2009. Stationery Office, London2010http://www.statistics.gov.uk/downloads/theme_health/dr2009/dr-09.pdfGoogle Scholar, 4Antithrombotic Trialists' (ATT) CollaborationAspirin in the primary and secondary prevention of vascular disease: collaborative meta-analysis of individual participant data from randomised trials.Lancet. 2009; 373: 1849-1860Summary Full Text Full Text PDF PubMed Scopus (2739) Google Scholar, 5Law MR Wald NJ Rudnicka AR Quantifying the effect of statins on low density lipoprotein cholesterol, ischaemic heart disease, and stroke: systematic review and meta-analysis.BMJ. 2003; 326: 1423-1427Crossref PubMed Google Scholar, 6Wald NJ Law MR A strategy to reduce cardiovascular disease by more than 80%.BMJ. 2003; 326: 1419-1423Crossref PubMed Google Scholar CVD incidence rates taken from reference 2Law M Wald N Morris J Lowering blood pressure to prevent myocardial infarction and stroke: a new preventive strategy.Health Technol Assess. 2003; 7: 31Crossref Scopus (225) Google Scholar (assuming 10% of strokes occur in people who have already had an ischaemic heart disease [IHD] event and vice versa); cancer mortality rates taken from reference 3Office for National StatisticsMortality statistics: deaths registered in 2009. Stationery Office, London2010http://www.statistics.gov.uk/downloads/theme_health/dr2009/dr-09.pdfGoogle Scholar. Relative risks associated with aspirin: IHD 0·77,4Antithrombotic Trialists' (ATT) CollaborationAspirin in the primary and secondary prevention of vascular disease: collaborative meta-analysis of individual participant data from randomised trials.Lancet. 2009; 373: 1849-1860Summary Full Text Full Text PDF PubMed Scopus (2739) Google Scholar stroke 0·95,4Antithrombotic Trialists' (ATT) CollaborationAspirin in the primary and secondary prevention of vascular disease: collaborative meta-analysis of individual participant data from randomised trials.Lancet. 2009; 373: 1849-1860Summary Full Text Full Text PDF PubMed Scopus (2739) Google Scholar cancer (after 5 years of use) 0·66.5Law MR Wald NJ Rudnicka AR Quantifying the effect of statins on low density lipoprotein cholesterol, ischaemic heart disease, and stroke: systematic review and meta-analysis.BMJ. 2003; 326: 1423-1427Crossref PubMed Google Scholar Relative risks associated with statins: IHD (only after 3 years of use) 0·39,5Law MR Wald NJ Rudnicka AR Quantifying the effect of statins on low density lipoprotein cholesterol, ischaemic heart disease, and stroke: systematic review and meta-analysis.BMJ. 2003; 326: 1423-1427Crossref PubMed Google Scholar stroke 0·87,5Law MR Wald NJ Rudnicka AR Quantifying the effect of statins on low density lipoprotein cholesterol, ischaemic heart disease, and stroke: systematic review and meta-analysis.BMJ. 2003; 326: 1423-1427Crossref PubMed Google Scholar cancer 1·00. Relative risks associated with three blood-pressure-lowering agents: IHD 0·64,6Wald NJ Law MR A strategy to reduce cardiovascular disease by more than 80%.BMJ. 2003; 326: 1419-1423Crossref PubMed Google Scholar stroke 0·37,6Wald NJ Law MR A strategy to reduce cardiovascular disease by more than 80%.BMJ. 2003; 326: 1419-1423Crossref PubMed Google Scholar cancer 1·00. Aspirin-induced major extracranial bleeds=three per 10 000 per year.4Antithrombotic Trialists' (ATT) CollaborationAspirin in the primary and secondary prevention of vascular disease: collaborative meta-analysis of individual participant data from randomised trials.Lancet. 2009; 373: 1849-1860Summary Full Text Full Text PDF PubMed Scopus (2739) Google Scholar Aspirin causes substantially fewer major extracranial bleeds that require a blood transfusion than the number of CVD events and cancer deaths prevented (table). However, the risk of an aspirin-induced major extracranial bleed increases with age.4Antithrombotic Trialists' (ATT) CollaborationAspirin in the primary and secondary prevention of vascular disease: collaborative meta-analysis of individual participant data from randomised trials.Lancet. 2009; 373: 1849-1860Summary Full Text Full Text PDF PubMed Scopus (2739) Google Scholar The estimates for such bleeds shown in the table among people aged 55 years over a period of 20 years are based on observed data and are likely to be accurate, but the numbers in people older than 75 years are uncertain—they would be twice those shown if the age trend to 75 years continues to 90 years. Given the results published by Rothwell and colleagues,1Rothwell PM Fowkes FG Belch JF Ogawa H Warlow CP Meade TW Effect of daily aspirin on long-term risk of death due to cancer: analysis of individual patient data from randomised trials.Lancet. 2011; 377: 31-41Summary Full Text Full Text PDF PubMed Scopus (1184) Google Scholar the balance of the evidence is in favour of including aspirin in a Polypill strategy to prevent CVD and cancer. NW and ML hold a European and Canadian patent (pending in the USA) for the Polypill, filed in April 2000. Aspirin in the prevention of cancer – Author's replyWe agree with N J Wald and colleagues that our results and their analyses do suggest that aspirin should be included in Polypill regimens, although the balance of risk and benefit is less certain in older individuals owing to the increase in risk of bleeding with age. Full-Text PDF