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Statin Use Cancer Related Mortality M Wilmath Nov2012 Whh Adult Med
 

Statin Use Cancer Related Mortality M Wilmath Nov2012 Whh Adult Med

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Review of NEJM Nov 2012 article on statins and cancer

Review of NEJM Nov 2012 article on statins and cancer

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  • According to the National Institutes of Health, cancer cost the U.S. an estimated $219 billion in 2007, including $130 billion for lost productivity and $89 billion in direct medical costs.Each year: • Colorectal cancer treatment costs about $8.4 billion. • Breast cancer treatment costs nearly $7 billion. • Cervical cancer treatment costs about $160 million
  • Note: The numbers in parentheses are the age-adjusted (U.S. standard) rates per 100,000 people.Cancer Among MenThe three most common cancers among men include:Prostate cancer (144.8): 1st among men of all races and Hispanic origin populations.Lung cancer (79.5): 2nd among white, black, American Indian/Alaska Native, and Asian/Pacific Islander men; third among Hispanic men.Colorectal cancer (51.6): 2nd among Hispanic men; third among white, black, American Indian/Alaska Native, and Asian/Pacific Islander men.Cancer Among WomenThe three most common cancers among women include:Breast cancer (121.9): 1st among women of all races and Hispanic origin populations.Lung cancer (54.5): 2nd among white, black, and American Indian/Alaska Native women, 3rd among Asian/Pacific Islander and Hispanic women.Colorectal cancer (38.7): 2nd among Asian/Pacific Islander and Hispanic women;3rd among white, black, and American Indian/Alaska Native women.
  • Note: The numbers in parentheses are the age-adjusted (U.S. standard) rates per 100,000 people.Cancer Among MenThe leading causes of cancer death among men are:Lung cancer (64.0): First among men of all racial and Hispanic origin populations.Prostate cancer (22.8): Second among white, black, American Indian/Alaska Native, Hispanic men; fourth among Asian/Pacific Islander men.Liver cancer: Second among Asian/Pacific Islander men.Colorectal cancer (19.7): Third among men of all races and Hispanic origin populations.The leading causes of cancer death among women are:Lung cancer (39.0): First among white, black, Asian/Pacific Islander, and American Indian/Alaska Native women, 2nd among Hispanic women.Breast cancer (22.5): 1st among Hispanic women, 2nd among white, black, Asian/Pacific Islander, American Indian/Alaska Native women.Colorectal cancer (13.8): Third among women of all races and Hispanic origin populations.
  • We assessed mortality among pt from the entire Danish population who had received a diagnosis of CA between 1995 & 2007, with follow-up until December 31, 2009. Among pt 40 years of age or older, 18,721 had used statins regularly before the CA diagnosis & 277,204 had never used statins.
  • Note that the study enrolled all pt with CA in Denmark from 1995 to 2007 & compared death rates among those who were taking statins at the time of the CA diagnosis to those who were not taking statins.
  • Analysis showed that:The cumulative incidence of death from CA, as a function of follow-up time, was significantly lower among statin users than among pt who had never used statins, with a log-rankP<0.001.The multivariable hazard ratio was 0.85, with 95% confidence interval from 0.83 to 0.87.Outcomes were similar regardless of the dose of statin given.
  • Multivariable-adjusted hazard ratios for statin users, as compared with pt who had never used statins, were 0.85 (95% confidence interval [CI], 0.83 to 0.87) for death from any cause & 0.85 (95% CI, 0.82 to 0.87) for death from CA. Adjusted hazard ratios for death from any cause according to the defined daily statin dose (the assumed average maintenance dose per day) were 0.82 (95% CI, 0.81 to 0.85) for a dose of 0.01 to 0.75 defined daily dose per day, 0.87 (95% CI, 0.83 to 0.89) for 0.76 to 1.50 defined daily dose per day, & 0.87 (95% CI, 0.81 to 0.91) for higher than 1.50 defined daily dose per day; the corresponding hazard ratios for death from CA were 0.83 (95% CI, 0.81 to 0.86), 0.87 (95% CI, 0.83 to 0.91), & 0.87 (95% CI, 0.81 to 0.92). The reduced CA-related mortality among statin users as compared with those who had never used statins was observed for each of 13 CA types.
  • Analysis showed that:During 1,072,503 person-years of follow-up, 162,067 pt died of CA, 14,489 of cardiovascular causes, & 19,038 of other causes, the researchers reported.
  • positive relationship btwn dose & response evidence of cause/effect.just an observational study, so exact dose &MOA can't clarify in this analysis
  • Routine screening can reduce the number of people who die from colorectal cancer by at least 60%. • A mammogram performed every 1–2 years for women aged 40 years and over can reduce mortality by approximately 20%–25% during a 10-year period. • Pap tests can detect precancerous lesions so they can be treated before cervical cancer develops. Researchers in many countries found that rates of cervical cancer death dropped by 20%–60% after screening programs began.Health economists generally agree that an intervention is cost effective if it can save 1 year of life for less than $50,000. Screening for colorectal, breast, and cervical cancers is indisputably cost effective: • Screening for colorectal cancer extends life at a cost of $11,890 to $29,725 per year of life saved. • A mammogram every 2 years extends life for women aged 65 or older at a cost of about $36,924 per year of life saved. • Pap screening every 3 years extends life at a cost of about $5,392 per year of life saved.
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Statin Use Cancer Related Mortality M Wilmath Nov2012 Whh Adult Med Statin Use Cancer Related Mortality M Wilmath Nov2012 Whh Adult Med Presentation Transcript

  • SF Nielsen, BG Nodrsetgaard, and SE BojesenA Review of New England Journal Of Medicine Article 2012: 237: 1792-1802 Presented by: Mario Wilmath
  • • Discuss disease state• Convey study purpose• Review study design and population• Evaluate study results• Discuss conclusions• Discuss strength, limitations, clinical value
  • • Previous meta-analysis suggested a relationship between statin use and decreased progression of colon, esophageal, and prostate CA• Denmark possesses a unified, complete database encompassing Cancer Registry, Death Registry, Prescriptions, and Comprehensive History• Statins are commonly prescribed and generically available
  • • “A reduction in the availability of cholesterol may limit the cellular proliferation required for CA growth & metastasis. We tested the hypothesis that statin use begun before a CA diagnosis is associated with reduced CA-related mortality.”
  • www.cancerresearchuk.org/cancer.../cancerstats/mortality/cancerdeat... www.conferenceboard.ca › ... › Details and Analysis › Health
  • U.S. Cancer Statistics Working Group. United States Cancer Statistics: 1999–2008 Incidence andMortality Web-based Report. Atlanta: U.S. Department of Health and Human Services, Centersfor Disease Control and Prevention and National Cancer Institute; 2012. Availableat:www.cdc.gov/uscs.
  • 20. Perinatal Period Conditions 10. Chronic Liver Disease19. Aortic Aneurysm & Dissection 9. Suicide18. Pneumonitis 8. Nephritis17. HIV 7. Alzheimers16. Homicide 6. DM215. Benign tumor 5. CVA14. Parkinsons Disease 4. Unintentional Injury13. Hypertension 3. Chronic Lower Respiratory Disease12. Septicemia 2. CANCER11. Influenza & Pneumonia 1. Heart Disease Thompson-Reuters 2012
  • • Primary: Determine extent of association between statin users and decreased cancer- related mortality• Secondary: Determine dose relationship of statin use to mortality• Safety: None• Other: Generate further hypotheses
  • Retrospective cohort analysis with further 1:3 nesting of subgroupsCohorts divided into statin users vs. non-statin users
  • • INCLUSION – 40 years of age – Diagnosis of cancer – Diagnosis occurred between 1995-2007• EXCLUSION: <40 years of age
  • • Statistics Denmark conducted analysis• Blinding of cancer diagnosis to statin use• Blinding of statin use to cancer diagnosis• Calculations performed using Strata Software, version 12.0MP
  • • Any statin use within 6 months of diagnosis• Nesting with age, sex, cancer matching due to changes in statin use over timeframe• Subgroups of cardiovascular and diabetes• Subgroups of statin dose, total of 4 strata• Cumulative Incidence Curves• Multivariate Cox Regression model analysis
  • Hazard ratios for statin users: • 0.85 (95% CI, 0.83 to 0.87) for death from any cause • 0.85 (95% CI, 0.82 to 0.87) for death from CAAdjusted hazard ratios for death from any cause according to the defined daily statin dose: • 0.82 (95% CI, 0.81 to 0.85) for a dose of 0.01 to 0.75 defined daily dose per day • 0.87 (95% CI, 0.83 to 0.89) for 0.76 to 1.50 defined daily dose per day • 0.87 (95% CI, 0.81 to 0.91) for higher than 1.50 defined daily dose per dayAdjusted hazard ratios for death from cancer according to the defined daily statin dose: : • 0.83 (95% CI, 0.81 to 0.86) • 0.87 (95% CI, 0.83 to 0.91) • 0.87 (95% CI, 0.81 to 0.92)Reduced mortality among statin users observed for 13 CA types
  • • Cumulative incidence of death from cancer, as a function of follow-up time, significantly lower in statin users than those who had never used statins (log-rankP<0.001).• Multivariable hazard ratio 0.85 (95% confidence interval from 0.82 to 0.87).• Cumulative incidence of death from any cause lower ( log-rank P<0.001).• Multivariable hazard ratio 0.85 (95% confidence interval from 0.83 to 0.87).• Outcomes similar regardless of statin dose given.
  • • Some studies suggest cancer cells need cholesterol• Lack of cholesterol shown to inhibit tumor growth• Did not address if statins can prevent cancer• Lower dose had higher survival than higher doses• Dose trend absence indicates some statin effect
  • When researchers examined deaths from all CAs, they found that pts w/ a history of statin use had a 15% lower risk of dying than those who had not used drugs
  • • Missing info about treatment, tumor size, & spread• Higher likelihood statin users had heart disease & might have also been targeted for smoking cessation• Chemo/radiation data missing for 72 % statin group• Homogeneous Danish population, not generalizable• Increased health awareness possible with statin use
  • 1.Basic research into plausible cause and effect2.Need to examine existing research to determine agent, dose, & duration of follow-up for a more powerful & convincing study3.Population studies needed to extend the results beyond Denmark
  • Researchers did not report any external support
  • 1. Statin use is associated with reduced CA-related mortality.2. This is only a preliminary, observational study.3. Cancer patients from 1995-2007 did not include newer agents.4. The potential benefits of statin therapy have highest correlation to colon, liver, esophageal, & prostate cancer.5. Chemopreventive benefits of statins even greater among patients using ASA or NSAIDs in other meta-analyses.6. Cancer prevention and treatment involves a inter-disciplinary approach to include diet, risk factor modification, medicinal, socio-cultural preference, and education.
  • 1. American CA Society American Institute for CA Research Medical News Today2. Caporaso NE "Statins & CA-related mortality -- lets work together" N Engl J Med 2012; 367: 1848-1850.3. Michaud, D.New England Journal of Medicine, May 6, 1999.Ohio State U.Exten4. Nielsen SF, et al "Statin use & reduced CA-related mortality" N Engl J Med 2012; 367: 1792- 1802.5. Charles Bankhead. “Statins May Cut Esophageal Cancer Risk.” MedPage Today Published: October 22, 20126. Algara A., Rothwell PM. “Effects of regular aspirin on long-term cancer incidence and metastasis: A systematic comparison of evidence from observational studies versus randomised trials.” The Lancet Oncology, Volume 13, Issue 5, Pages 518 - 527, May 2012. doi:10.1016/S1470-2045(12)70112-2 Published Online: 21 March 20127. PM Rothwell, et al. Effect of daily aspirin on long-term risk of death due to cancer: Analysis of individual patient data from randomised trials. The Lancet, Volume 377, Issue 9759, Pages 31 - 41, 1 January 2011. doi:10.1016/S0140-6736(10)62110-18. Pradelli D, et al. Statins and primary liver cancer: A meta-analysis of observational studies. European Journal of CA Prevention. 2012 June 28; doi: 10.1097CEJ06013e.9. United States Cancer Statistics: 2008 Incidence and Mortality report (USCS). Centers for Disease Control and Prevention Division of CA Prevention and Control. Accessed November 2012.
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