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Journal Club

This case presentation explores the potential benefits and risks of daily aspirin use for primary prevention of cardiovascular disease and cancer. It discusses the evidence from randomized controlled trials and provides recommendations based on current guidelines.

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Journal Club

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  1. Journal Club Benjamin Han June 7th, 2013

  2. Case Presentation Our patient is a 75 year old lady with hypertension, hyperlipidemia, and GERD who is doing well. She is seen in clinic to establish care. She wonders if she should take aspirin since her husband takes it.

  3. Case Presentation Past Medical History: • Hypertension • Hyperlipidemia • Cataracts • Essential Tremor • Left Knee OA s/p knee replacement in 2006 Family History: • Father died of prostate cancer in his 80s • Mother died of ovarian cancer in her 60s • Brother committed suicide

  4. Case Presentation Social History: • Born and raised in Cambridge, Mass. • Finished high school and worked in retail. • Married with five children. • Had moved to Nevada in 1990 with husband, decided to move back to Boston to be closer to family. • Lives with husband in Quincy, MA. Three children and seven grandchildren live nearby. • Very active, walks 1-2 miles a day. • Never smoker, never drinks ETOH.

  5. Case Presentation Medications: • HCTZ 25 mg daily • Lovastatin 40 mg daily • Omeprazole 20 mg daily • Vitamin D 1000 units daily • Tylenol PRN • Loratadine 10 mg daily • Flonase PRN

  6. Case Presentation Physical Exam: VS: BP 106/74, HR 78 Cardiac, pulmonary, neurological exam is unremarkable. MMSE 30/30 Lab Work: A1c: 5.9 LDL 128 Cholesterol: 208 HDL 61

  7. Case Presentation Cancer Screenings: • Recent pap smear and mammogram normal in Nevada. • Never wants a colonoscopy, ever. Her husband had a bad experience with his colonoscopy.

  8. Case Presentation We calculate her Framingham Risk Score for 10-year cardiovascular risk to be 8.62%. D'Agostino RB Sr, Vasan RS, Pencina MJ, et. al. General Cardiovascular Risk Profile for Use in Primary Care. The Framingham Heart Study. Circulation. 2008 Jan 22.

  9. Case Presentation Should she get a daily ASA for primary prevention?

  10. Case Presentation • A 20 percent relative risk reduction in non-fatal myocardial infarction (MI) (OR 0.80, 95% CI 0.67-0.96). • No significant impact on non-fatal stroke (including ischemic and hemorrhagic stroke). • No significant impact on CVD mortality. • A 54 percent increase in the relative risk of non-fatal extracranial bleeding (RR 1.54, 95% CI 01.30-1.82). “For low-risk patients (ie, men and women whose 10 year absolute risk of a first coronary heart disease event is <10 percent), the absolute benefit of a reduction in cardiovascular events is unlikely to exceed the absolute risk of major bleeding.” Seshasai SR, Wijesuriya S, Sivakumaran R, et al. Effect of aspirin on vascular and nonvascular outcomes: meta-analysis of randomized controlled trials. Arch Intern Med 2012; 172:209. 8 Antithrombotic Trialists' (ATT) Collaboration, Baigent C, Blackwell L, et al. Aspirin in the primary and secondary prevention of vascular disease: collaborative meta-analysis of individual participant data from randomised trials. Lancet 2009; 373:1849.

  11. Case Presentation 2012 – American College of Chest Physicians suggest the use of low-dose ASA for persons >50 without symptomatic CV disease. 2012 - European Society of Cardiology advises against use of ASA or clopidogrel in individuals without CV disease due to risk of major bleeding. 2009 – USPSTF in individuals for whom the potential harm of GI hemorrhage does not outweigh potential benefit. • Men aged 45-79 for prevention of MI • Women 55-79 for prevention of CVA

  12. Case Presentation Are there any other benefits to taking daily aspirin other than cardiovascular prevention that would further outweigh the potential harm of an increase in bleeding?

  13. Aspirin for cancer prevention?

  14. Background Case-control and cohort studies have suggested that daily aspirin may inhibit colorectal carcinogenesis, metastases, and related mortality, particularly gastrointestinal cancers (colorectal). Possible mechanisms: - Induction of cell apoptosis. - Inhibition of COX-related prostaglandin production.

  15. Background In 2007 the US Preventive Services Task Force (USPSTF) in a systematic review of cohort studies found that regular use of higher doses of ASA >325 mg/d was associated with a 22% RRR in incidence of colorectal ca. However, two large RCT (WHS, PHS) failed to demonstrate a reduction in colorectal ca or reductions in mortality had not been established: USPSTF did not recommend routine ASA for primary prevention of CRC.

  16. Background Numerous randomized trials have evaluated the role of ASA in primary and secondary prevention of CV disease, and now long-term follow-up from these trials give the opportunity to explore if ASA is associated with risks of cancer.

  17. Background Rothwell PM, Wilson M, Elwin CE, et al. Long-term effect of aspirin on colorectal cancer incidence and mortality: 20-year follow-up of five randomized trials. Lancet. 2010;376:1741-50. Low dose ASA taken for >5 years lowered the incidence of colorectal ca and related mortality after a latent period of 10-20 years. Short-term effects and inclusion of studies with large numbers of female had not yet been examined.

  18. Aspirin and Cancer

  19. Aspirin and Cancer Clinical question: What are the short-term effects of daily aspirin on cancer incidence and mortality?

  20. Aspirin and Cancer Clinical questions: What are the effects of aspirin on risk of cancer in women? What are the overall balance of risk and benefit of daily low-dose aspirin in primary prevention?

  21. Aspirin and Cancer Review Methods: • Multiple databases searched for randomized controlled trials of aspirin. • Intervention: Daily aspirin, sub-analysis in patients on low-dose ASA. • All analyses were intention-to-treat. • Control: Placebo.

  22. Aspirin and Cancer Scope of meta-analysis: • Included studies compared daily ASA with no ASA. • Excluded: Use of other antiplatelets (plavix), short-term use of ASA (<90 days), and studies of secondary prevention or treatment of cancer or colonic polyps. • Outcomes chosen: • All Trials: Death due to cancer, all non-vascular death, vascular death, and all deaths. • When available: Incident cancer, major vascular events, and major extracranial bleeds.

  23. Aspirin and Cancer Review Methods: 51 RCTs of primary and secondary prevention of vascular disease (n=77,549 patients, mean follow up of 0.5 to 8.2 years). Cancer mortality data available for 34 trials (n=69,224). There were 12 primary prevention trials (n=42,356). Individual patient data were available for 6 primary prevention trials of low dose ASA (n=35,535).

  24. Aspirin and Cancer

  25. Aspirin and Cancer

  26. Results

  27. Results

  28. Results

  29. Results Aspirin reduced risk for cancer mortality and nonvascular mortality. Meta-analysis of primary prevention trials showed that ASA reduced risk for nonvascular mortality but not vascular mortality. The number of specific cancers was too small to establish effects of ASA on specific cancer types.

  30. Limitations Does not include the largest randomized trails in primary prevention: • Women’s Health Study (n=39,876) – alternate day 100 mg ASA used over 10 years. • Physicians’ Health Study (n=22,071) - alternate day 325 mg ASA used over 5 years. These were not associated with reduced risk of cancer incidence or mortality.

  31. Limitations These studies were designed to examine cardiovascular endpoints, not cancer screening or surveillance therefore cancer events may have been under-reported. Further information needed regarding risks/benefits in older adults.

  32. Discussion • For your older patients with borderline (or no) vascular indication for ASA for primary prevention, does the prospect of short-term cancer prevention sway your decision?

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