BACKGROUND: Colorectal cancer (CRC) is the third most commonly diagnosed cancer in both men and women in the United States (U.S.). Aspirin may inhibit CRC development and related mortality.
PURPOSE: We conducted this systematic evidence review on aspirin use for the prevention of CRC to support the U.S. Preventive Services Task Force (USPSTF) in updating its previous recommendation. Our review addressed four key questions in adults without a history of CRC, familial adenomatous polyposis, or Lynch Syndrome: 1) Does regular aspirin use reduce CRC mortality or all-cause mortality? 2) Does regular aspirin use reduce the incidence of CRC? 3) Does regular aspirin use reduce the incidence of colorectal adenoma? 4) What are the harms of regular aspirin use for the prevention of colorectal cancer?
DATA SOURCES: We performed a search of MEDLINE, PubMed, and the Cochrane Collaboration Registry of Controlled Trials for studies published from January 2004 through May 2014. We supplemented searches by examining bibliographies from previous systematic reviews, retrieved articles, and the previous USPSTF review. We searched federal agency trial registries for ongoing and/or unpublished trials.
STUDY SELECTION: We conducted a dual review of 865 abstracts against prespecified inclusion criteria. We retrieved 149 potentially relevant articles, which two reviewers independently evaluated using well-defined inclusion/exclusion criteria and critically appraised for risk of bias. Discrepancies were resolved by discussion with a third reviewer.
DATA EXTRACTION AND ANALYSIS: For all fair-quality and good-quality studies, a single investigator extracted study characteristics and outcomes into structured tables and a second investigator verified accuracy. Elements abstracted for each study included study design, population characteristics, sample sizes, exposures, outcomes, and measures of association. We created summary evidence tables to capture key study characteristics and sources of heterogeneity. In addition to the overall results for each included study, we also presented results by dose, duration, latency, and adenoma history where possible. We used forest plots stratified by potentially important exposure and study characteristics to visually identify patterns in the study results and help determine if pooling across studies was appropriate. We used the Mantel-Haenszel fixed effects model to estimate the combined effect and confidence interval; for very rare events (incidence less than one percent), we calculated the Peto odds ratio.
RESULTS: Daily or alternate-day aspirin at ≥75 mg was associated with a small reduction in all-cause mortality risk in the first 10 years after randomization (summary relative risk, RR, 0.94, [95% confidence interval, CI, 0.89 to 0.99]) in 11 randomized controlled trials (RCTs) among persons in the general population (i.e., selected without considering their adenoma history). Over a 20+ year period, aspirin appeared to reduce the risk of CRC mortality by approximately 33%. However, long-term data on CRC mortality may have limited applicability, particularly from the perspective of a low-dose aspirin benefits in a primary CVD population addressing women as well as men. Two of four trials were in those with pre-existing cardiovascular disease and two involved dosages of 500 mg or greater daily, with no longer-term mortality results available for alternate-day regimens. Data on mortality among persons with a prior colorectal adenoma were also sparse. Six RCTs of aspirin for primary and secondary CVD prevention provided data on the effect of regular aspirin use on invasive CRC incidence in the general population. In this population, aspirin had no effect on CRC incidence in the first 10 years following randomization, but reduced CRC incidence by approximately 40 percent after a latency of 10 years (summary RR, 0.60 [95% CI, 0.47 to 0.76]). Over a 20+ year period, aspirin appeared to reduce the risk of CRC incidence by approximately 20 to 24%. Data on aspirin use and CRC incidence in persons with a prior adenoma were limited and represented only short-term followup (fewer than 5 years) and could not, therefore, provide sufficient information on the effect of aspirin use on CRC incidence. In persons with a prior adenoma, data were conflicting, but there was some suggestion of a decreased risk of adenoma incidence over a 3- to 4- year period. Data on aspirin and adenoma risk in the general population were sparse. Data from RCTs suggested that aspirin increased the risk of serious gastrointestinal bleeding (summary OR, 1.94 [95% CI, 1.44 to 2.62]), intracranial bleeding (summary OR, 1.53 [95% CI, 1.21 to 1.93]), and hemorrhagic stroke (summary OR, 1.47 [95% CI, 1.16 to 1.88]), but not fatal gastrointestinal bleeding (summary OR, 1.00 [95% CI, 0.43 to 2.36]).
LIMITATIONS: Limited data were available to address differences in possible effects of aspirin in subgroups (e.g., age, sex, race) or to compare daily vs. alternate-day aspirin use. Long-term followup data were not identified for persons with a history of adenoma.
CONCLUSIONS: Aspirin appears to reduce the risk of CRC incidence after an induction and latency period of approximately 10 years, with a similar effect on CRC mortality. The applicability of data for long-term effects of low-dose aspirin on CRC mortality, however, is limited, particularly in the context of a population selected for primary CVD prevention. Aspirin does not appear to have a strong effect on all-cause mortality within 10 years of initiating use, and data on long-term cumulative risk of all-cause mortality were sparse.
Broad synthesis/ Overview of systematic reviews/ Systematic review
BACKGROUND: This guideline addresses the management of patients who are receiving anticoagulant or antiplatelet therapy and require an elective surgery or procedure.
METHODS: The methods herein follow those discussed in the Methodology for the Development of Antithrombotic Therapy and Prevention of Thrombosis Guidelines. Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines article of this supplement.
RESULTS: In patients requiring vitamin K antagonist (VKA) interruption before surgery, we recommend stopping VKAs 5 days before surgery instead of a shorter time before surgery (Grade 1B). In patients with a mechanical heart valve, atrial fibrillation, or VTE at high risk for thromboembolism, we suggest bridging anticoagulation instead of no bridging during VKA interruption (Grade 2C); in patients at low risk, we suggest no bridging instead of bridging (Grade 2C). In patients who require a dental procedure, we suggest continuing VKAs with an oral prohemostatic agent or stopping VKAs 2 to 3 days before the procedure instead of alternative strategies (Grade 2C). In moderate- to high-risk patients who are receiving acetylsalicylic acid (ASA) and require noncardiac surgery, we suggest continuing ASA around the time of surgery instead of stopping ASA 7 to 10 days before surgery (Grade 2C). In patients with a coronary stent who require surgery, we recommend deferring surgery > 6 weeks after bare-metal stent placement and > 6 months after drug-eluting stent placement instead of undertaking surgery within these time periods (Grade 1C); in patients requiring surgery within 6 weeks of bare-metal stent placement or within 6 months of drug-eluting stent placement, we suggest continuing antiplatelet therapy perioperatively instead of stopping therapy 7 to 10 days before surgery (Grade 2C).
CONCLUSIONS: Perioperative antithrombotic management is based on risk assessment for thromboembolism and bleeding, and recommended approaches aim to simplify patient management and minimize adverse clinical outcomes.
OBJECTIVES: To update a previous report on the comparative benefits and harms of oral non-steroidal anti-inflammatory drugs (NSAIDs), acetaminophen, over-the-counter supplements (chondroitin and glucosamine), and topical agents (NSAIDs and rubefacients, including capsaicin) for osteoarthritis.
DATA SOURCES: Ovid MEDLINE (1996–January 2011), the Cochrane Database (through fourth quarter 2010), and reference lists.
REVIEW METHODS: We included randomized trials, cohort studies, case-control studies, and systematic reviews that met predefined inclusion criteria. For each study, investigators abstracted details about the study population, study design, data analysis, followup, and results, and they assessed quality using predefined criteria. We assessed the overall strength of each body of evidence using predefined criteria, which included the type and number of studies; risk of bias; consistency; and precision of estimates. Meta-analyses were not performed, though pooled estimates from previously published studies were reported.
RESULTS: A total of 273 studies were included. Overall, we found no clear differences in efficacy for pain relief associated with different NSAIDs. Celecoxib was associated with a lower risk of ulcer complications (RR 0.23, 95% CI 0.07 to 0.76) compared to nonselective NSAIDs. Coprescribing of proton pump inhibitors, misoprostol, and H2-antagonists reduce the risk of endoscopically detected gastroduodenal ulcers compared to placebo in persons prescribed NSAIDs. Celecoxib and most nonselective, nonaspirin NSAIDs appeared to be associated with an increased risk of serious cardiovascular (CV) harms. There was no clear association between longer duration of NSAID use or higher doses and increased risk of serious CV harms. There were no clear differences between glucosamine or chondroitin and oral NSAIDs for pain or function, though evidence from a systematic review of higher-quality trials suggests that glucosamine had some very small benefits over placebo for pain. Head-to-head trials showed no difference between topical and oral NSAIDs for efficacy in patients with localized osteoarthritis, lower risk of gastrointestinal (GI) adverse events, and higher risk of dermatological adverse events, but serious GI and CV harms were not evaluated. No head-to-head trials compared topical salicylates or capsaicin to oral NSAIDs.
CONCLUSIONS: Each of the analgesics evaluated in this report was associated with a unique set of risks and benefits. Choosing the optimal analgesic for an individual with osteoarthritis requires careful consideration and thorough discussion of the relevant tradeoffs.
Colorectal cancer (CRC) is the third most commonly diagnosed cancer in both men and women in the United States (U.S.). Aspirin may inhibit CRC development and related mortality.
PURPOSE:
We conducted this systematic evidence review on aspirin use for the prevention of CRC to support the U.S. Preventive Services Task Force (USPSTF) in updating its previous recommendation. Our review addressed four key questions in adults without a history of CRC, familial adenomatous polyposis, or Lynch Syndrome: 1) Does regular aspirin use reduce CRC mortality or all-cause mortality? 2) Does regular aspirin use reduce the incidence of CRC? 3) Does regular aspirin use reduce the incidence of colorectal adenoma? 4) What are the harms of regular aspirin use for the prevention of colorectal cancer?
DATA SOURCES:
We performed a search of MEDLINE, PubMed, and the Cochrane Collaboration Registry of Controlled Trials for studies published from January 2004 through May 2014. We supplemented searches by examining bibliographies from previous systematic reviews, retrieved articles, and the previous USPSTF review. We searched federal agency trial registries for ongoing and/or unpublished trials.
STUDY SELECTION:
We conducted a dual review of 865 abstracts against prespecified inclusion criteria. We retrieved 149 potentially relevant articles, which two reviewers independently evaluated using well-defined inclusion/exclusion criteria and critically appraised for risk of bias. Discrepancies were resolved by discussion with a third reviewer.
DATA EXTRACTION AND ANALYSIS:
For all fair-quality and good-quality studies, a single investigator extracted study characteristics and outcomes into structured tables and a second investigator verified accuracy. Elements abstracted for each study included study design, population characteristics, sample sizes, exposures, outcomes, and measures of association. We created summary evidence tables to capture key study characteristics and sources of heterogeneity. In addition to the overall results for each included study, we also presented results by dose, duration, latency, and adenoma history where possible. We used forest plots stratified by potentially important exposure and study characteristics to visually identify patterns in the study results and help determine if pooling across studies was appropriate. We used the Mantel-Haenszel fixed effects model to estimate the combined effect and confidence interval; for very rare events (incidence less than one percent), we calculated the Peto odds ratio.
RESULTS:
Daily or alternate-day aspirin at ≥75 mg was associated with a small reduction in all-cause mortality risk in the first 10 years after randomization (summary relative risk, RR, 0.94, [95% confidence interval, CI, 0.89 to 0.99]) in 11 randomized controlled trials (RCTs) among persons in the general population (i.e., selected without considering their adenoma history). Over a 20+ year period, aspirin appeared to reduce the risk of CRC mortality by approximately 33%. However, long-term data on CRC mortality may have limited applicability, particularly from the perspective of a low-dose aspirin benefits in a primary CVD population addressing women as well as men. Two of four trials were in those with pre-existing cardiovascular disease and two involved dosages of 500 mg or greater daily, with no longer-term mortality results available for alternate-day regimens. Data on mortality among persons with a prior colorectal adenoma were also sparse. Six RCTs of aspirin for primary and secondary CVD prevention provided data on the effect of regular aspirin use on invasive CRC incidence in the general population. In this population, aspirin had no effect on CRC incidence in the first 10 years following randomization, but reduced CRC incidence by approximately 40 percent after a latency of 10 years (summary RR, 0.60 [95% CI, 0.47 to 0.76]). Over a 20+ year period, aspirin appeared to reduce the risk of CRC incidence by approximately 20 to 24%. Data on aspirin use and CRC incidence in persons with a prior adenoma were limited and represented only short-term followup (fewer than 5 years) and could not, therefore, provide sufficient information on the effect of aspirin use on CRC incidence. In persons with a prior adenoma, data were conflicting, but there was some suggestion of a decreased risk of adenoma incidence over a 3- to 4- year period. Data on aspirin and adenoma risk in the general population were sparse. Data from RCTs suggested that aspirin increased the risk of serious gastrointestinal bleeding (summary OR, 1.94 [95% CI, 1.44 to 2.62]), intracranial bleeding (summary OR, 1.53 [95% CI, 1.21 to 1.93]), and hemorrhagic stroke (summary OR, 1.47 [95% CI, 1.16 to 1.88]), but not fatal gastrointestinal bleeding (summary OR, 1.00 [95% CI, 0.43 to 2.36]).
LIMITATIONS:
Limited data were available to address differences in possible effects of aspirin in subgroups (e.g., age, sex, race) or to compare daily vs. alternate-day aspirin use. Long-term followup data were not identified for persons with a history of adenoma.
CONCLUSIONS:
Aspirin appears to reduce the risk of CRC incidence after an induction and latency period of approximately 10 years, with a similar effect on CRC mortality. The applicability of data for long-term effects of low-dose aspirin on CRC mortality, however, is limited, particularly in the context of a population selected for primary CVD prevention. Aspirin does not appear to have a strong effect on all-cause mortality within 10 years of initiating use, and data on long-term cumulative risk of all-cause mortality were sparse.
