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Aspirin Use in Adults: Cancer, All-Cause Mortality, and Harms a Systematic Evidence Review for the U.S

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Aspirin Use in Adults: Cancer, All-Cause Mortality, and Harms a Systematic Evidence Review for the U.S Evidence Synthesis Number 132 Aspirin Use in Adults: Cancer, All-Cause Mortality, and Harms A Systematic Evidence Review for the U.S. Preventive Services Task Force Prepared for: Agency for Healthcare Research and Quality U.S. Department of Health and Human Services 540 Gaither Road Rockville, MD 20850 www.ahrq.gov Contract No. HHSA-290-2012-00151-I, Task Order No. 4 Prepared by: Kaiser Permanente Research Affiliates Evidence-based Practice Center Kaiser Permanente Center for Health Research Portland, OR Investigators: Evelyn P. Whitlock, MD, MPH Selvi B. Williams, MD, MPH Brittany U. Burda, MPH Alisha Feightner, MPH Tracy Beil, MS AHRQ Publication No. 13-05193-EF-1 September 2015 This systematic review was conducted in coordination with two other systematic reviews1,2 and a decision model3 to support the U.S. Preventive Services Task Force (USPSTF) in making updated clinical preventive service recommendations for aspirin in primary prevention. The original literature searches were completed in June 2014. In order to prepare a set of manuscripts derived from these reviews, we conducted updated literature searches through January 6, 2015 to identify newly published information since the original searches. A single open-label randomized, controlled clinical trial in a cardiovascular disease (CVD) primary prevention population—the Japanese Primary Prevention Project (JPPP)4—was the only additional clinical research report located through the updated searches that met inclusion/exclusion criteria for any of the reviews. Outcomes from this study (nonfatal myocardial infarction [MI], nonfatal stroke [nonfatal cerebral infarction, intracranial hemorrhage, and undefined cardiovascular events], CVD mortality [fatal MI, cerebral infarction, intracranial hemorrhage, subarachnoid hemorrhage, and other fatal cardiovascular events], hemorrhagic stroke [fatal and nonfatal intracranial hemorrhage], and all-cause mortality) were incorporated into the final evidence reviewed by the USPSTF and resulted in updated inputs into the decision analysis. This systematic review has NOT been updated to reflect the incorporation of results from JPPP. Updated results are reflected in the manuscript derived from this review, which is available for public comment at http://www.uspreventiveservicestaskforce.org. Results for this systematic review for outcomes unrelated to those reported in JPPP are current through January 6, 2015. No further updated literature searches have been undertaken. References 1. Chubak J, Kamineni A, Buist DS, et al. Aspirin Use for the Prevention of Colorectal Cancer: An Updated Systematic Evidence Review for the U.S. Preventive Services Task Force. Evidence Synthesis No. 133. AHRQ Publication No. 15-05228-EF-1. Rockville, MD: Agency for Healthcare Research and Quality; 2015. 2. Guirguis-Blake JM, Evans CV, Senger CA, et al. Aspirin for the Primary Prevention of Cardiovascular Events: A Systematic Evidence Review for the U.S. Preventive Services Task Force. Evidence Synthesis No. 131. Rockville, MD: Agency for Healthcare Research and Quality; 2015. 3. Dehmer SP, Maciosek MV, Flottemesch TJ. Aspirin Use to Prevent Cardiovascular Disease and Colorectal Cancer: A Decision Analysis. AHRQ Publication No. 15-05229-EF-1. Rockville, MD: Agency for Healthcare Research and Quality; 2015. 4. Ikeda Y, Shimada K, Teramoto T, et al. Low-dose aspirin for primary prevention of cardiovascular events in Japanese patients 60 years or older with atherosclerotic risk factors: a randomized clinical trial. JAMA. 2014;312(23):2510-20. PMID: 25401325. Aspirin and Cancer, All-Cause Mortality, and Harms ii Kaiser Permanente Research Affiliates EPC This report is based on research conducted by the Kaiser Permanente Research Affiliates Evidence-based Practice Center (EPC) under contract to the Agency for Healthcare Research and Quality (AHRQ), Rockville, MD (Contract No. HHSA-290-2012-00151-I, Task Order No. 4). The findings and conclusions in this document are those of the authors, who are responsible for its contents, and do not necessarily represent the views of AHRQ. Therefore, no statement in this report should be construed as an official position of AHRQ or of the U.S. Department of Health and Human Services. The information in this report is intended to help health care decisionmakers—patients and clinicians, health system leaders, and policymakers, among others—make well-informed decisions and thereby improve the quality of health care services. This report is not intended to be a substitute for the application of clinical judgment. Anyone who makes decisions concerning the provision of clinical care should consider this report in the same way as any medical reference and in conjunction with all other pertinent information, i.e., in the context of available resources and circumstances presented by individual patients. This report may be used, in whole or in part, as the basis for development of clinical practice guidelines and other quality enhancement tools, or as a basis for reimbursement and coverage policies. AHRQ or U.S. Department of Health and Human Services endorsement of such derivative products may not be stated or implied. This document is in the public domain and may be used and reprinted without permission except those copyrighted materials that are clearly noted in the document. Further reproduction of those copyrighted materials is prohibited without the specific permission of copyright holders. None of the investigators has any affiliations or financial involvement that conflicts with the material presented in this report. Acknowledgments The authors acknowledge the following individuals for their contributions to this project: Robert McNellis, PA, MPH, at AHRQ; current and former members of the U.S. Preventive Services Task Force who contributed to topic deliberations; Luis Alberto Garcia Rodriguez, MD, MS, Barnett Kramer, MD, MPH, Diana Petitti, MD, MPH, Peter Rothwell, MD, Steven Teutsch, MD, MPH, and Asad Umar, DVM, PhD, for providing expert review; and Elizabeth O’Connor, PhD, Smyth Lai, MLS, Kevin Lutz, MFA, and Keshia Bigler, BS, at the Kaiser Permanente Center for Health Research. Suggested Citation Whitlock EP, Williams SB, Burda BU, Feightner A, Beil T. Aspirin Use in Adults: Cancer, All- Cause Mortality, and Harms. A Systematic Evidence Review for the U.S. Preventive Services Task Force. Evidence Synthesis No. 132. AHRQ Publication No. 13-05193-EF-1. Rockville, MD: Agency for Healthcare Research and Quality; September 2015. Aspirin and Cancer, All-Cause Mortality, and Harms iii Kaiser Permanente Research Affiliates EPC Structured Abstract Background: Cancer is the second leading cause of death in United States. The net benefit for aspirin (ASA) in cardiovascular disease (CVD) primary prevention is controversial due to increased risks from bleeding alongside relatively modest cardiovascular benefits. Consideration of additional cancer prevention effects might clarify whether long-term, low-dose ASA may offer an overall health benefit for the two top causes of mortality in the United States. Purpose: We conducted this review, alongside two companion reviews, to support the U.S. Preventive Services Task Force (USPSTF) in making evidence-based recommendations about the use of ASA for primary prevention in adults and to understand the risks of regular ASA use. Data Sources: We used a systematic evidence review published in 2012 for cancer-specific and all-cause mortality outcomes and conducted a bridge search of PubMed, MEDLINE, and the Cochrane Central Register of Controlled Trials from 2011 to October 2013. For bleeding harms, we used four published systematic evidence reviews and conducted a search of PubMed, MEDLINE, and the Cochrane Central Register of Controlled Trials from January 1, 2010 to June 3, 2014 in PubMed and MEDLINE. We also reviewed all studies included and excluded for companion USPSTF reviews on ASA for colorectal cancer and CVD prevention and checked for additional relevant studies by reviewing reference lists of included studies and other published reviews or meta-analyses. Study Selection: Two investigators independently reviewed 4,393 abstracts and 336 articles against previously established inclusion and exclusion criteria and critically appraised studies for risk of bias using USPSTF methods, supplemented by the Newcastle-Ottawa Scale for cohort studies and the Assessment of Multiple Systematic Reviews for systematic reviews. We included fair- or good-quality trials evaluating the effect of 75 mg or greater ASA at least every other day for 12 months or longer versus no ASA, in the absence of other antithrombotic medications, on cancer mortality, all-cause mortality, cancer incidence, and harms, primarily related to serious bleeding. We also included cohort studies meeting these criteria to evaluate potential harms of ASA. Data Extraction and Analysis: For fair- and good-quality studies, one investigator abstracted study characteristics and outcomes into structured tables and a second verified accuracy. We assessed trials for heterogeneity using I2 statistics and pooled trial-level results when appropriate using Mantel-Haenszel fixed effects to calculate relative risks (RRs) and Peto’s odds ratios (OR). We focused on cancer effects and bleeding harms in CVD primary prevention trials, but also assessed results after including secondary CVD and colorectal adenoma prevention trials. Expected outcome rates with ASA intervention were calculated by multiplying simulated control group event rates for benefits
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