The effect of antithrombotic treatment on the fecal immunochemical test for colorectal cancer screening: a nationwide cross-sectional study

Abstract

Background Screening for colorectal cancer (CRC) using the fecal immunochemical test (FIT) has been widely adopted. The use of antithrombotic treatment is increasing in the Western world. This study aimed to assess the effects of antithrombotic treatment on the FIT-based Danish national screening program for CRC.

Methods This was a cross-sectional study of all individuals returning a FIT from 2014 until 2016. The effect of antithrombotic treatment on FIT positivity and the positive predictive value (PPV) were assessed using proportions and multivariable Poisson regression.

Results Of 884 036 invited individuals, we identified 551 570 participants. A positive FIT was observed in 9052 of 77 007 individuals (11.8 %) receiving antithrombotic treatment compared with 28 387 of 474 587 individuals (6.0 %) receiving no treatment. The adjusted relative risk (RR) for a positive FIT was 1.59 (95 %CI 1.56–1.63) for any treatment. Nonvitamin K oral anticoagulants (NOACs) were associated with the largest increase in FIT positivity (adjusted RR 2.40, 95 %CI 2.48–2.54). The proportion of CRC detected at colonoscopy was slightly lower among patients on antithrombotic treatment (6.0 %, 95 %CI 5.5 %–6.6 %) than among treatment-naïve patients (6.4 %, 95 %CI 6.1 %–6.7 %). The PPV for CRC or high risk adenomas was decreased nearly twofold in patients treated with NOAC (adjusted RR 0.58, 95 %CI 0.51–0.66]).

Conclusion Antithrombotic treatment was associated with a decreased PPV in FIT-based CRC screening.

Publication History

Received: 22 April 2022

Accepted after revision: 02 November 2022

Article published online:
26 January 2023

• References

• 1 Ferlay J, Steliarova-Foucher E, Lortet-Tieulent J. et al. Cancer incidence and mortality patterns in Europe: Estimates for 40 countries in 2012. Eur J Cancer 2013; 49: 1374-1403
• 2 Siegel R, Ma J, Zou Z. et al. Cancer Statistics, 2014. CA Cancer J Clin 2014; 64: 9-29
• 3 Holme Ø, Bretthauer M, Fretheim A. et al. Flexible sigmoidoscopy versus faecal occult blood testing for colorectal cancer screening in asymptomatic individuals. Cochrane database Syst Rev 2013; 9: CD009259
• 4 Lin JS, Perdue LA, Henrikson NB. et al. Screening for colorectal cancer: updated evidence report and systematic review for the US Preventive Services Task Force. JAMA 2021; 325: 1978-1997
• 5 Chugh SS, Havmoeller R, Narayanan K. et al. Worldwide epidemiology of atrial fibrillation: a Global Burden of Disease 2010 Study. Circulation 2014; 129: 837-847
• 6 Angiolillo DJ, Goodman SG, Bhatt DL. et al. Antithrombotic therapy in patients with atrial fibrillation treated with oral anticoagulation undergoing percutaneous coronary intervention. Circulation 2018; 138: 527-536
• 7 Imperiale TF. Continue or discontinue warfarin for fecal occult blood testing in 2010? Does the published evidence provide an answer?. Am J Gastroenterol 2010; 105: 2036-2039
• 8 Sawhney MS, McDougall H, Nelson DB. et al. Fecal occult blood test in patients on low-dose aspirin, warfarin, clopidogrel, or non-steroidal anti-inflammatory drugs. Dig Dis Sci 2010; 55: 1637-1642
• 9 Kahi CJ, Rex DK, Imperiale TF. Screening, surveillance, and primary prevention for colorectal cancer: a review of the recent literature. Gastroenterology 2008; 135: 380-399
• 10 Faivre J, Dancourt V, Denis B. et al. Comparison between a guaiac and three immunochemical faecal occult blood tests in screening for colorectal cancer. Eur J Cancer 2012; 48: 2969-2976
• 11 Levi Z, Rozen P, Hazazi R. et al. Sensitivity, but not specificity, of a quantitative immunochemical fecal occult blood test for neoplasia is slightly increased by the use of low-dose aspirin, NSAIDS, and anticoagulants. Am J Gastroenterol 2009; 104: 933-938
• 12 Bujanda L, Sarasqueta C, Lanas Á. et al. Effect of oral anticoagulants on the outcome of faecal immunochemical test. Br J Cancer 2014; 110: 1334-1337
• 13 Mandelli G, Radaelli F, Paggi S. et al. Anticoagulant or aspirin treatment does not affect the positive predictive value of an immunological fecal occult blood test in patients undergoing colorectal cancer screening: results from a nested in a cohort case-control study. Eur J Gastroenterol Hepatol 2011; 23: 323-326
• 14 Randel KR, Botteri E, Romstad KMK. et al. Effects of oral anticoagulants and aspirin on performance of fecal immunochemical tests in colorectal cancer screening. Gastroenterology 2019; 156: 1642-1649.e1
• 15 Niikura R, Yamada A, Fujishiro M. et al. The effects of direct oral anticoagulants, warfarin, aspirin and thienopyridine on the performance of immunochemical, faecal, occult blood tests. Digestion 2019; 100: 117-126
• 16 Jung Y, Im E, Lee J. et al. Use of antiplatelet agents decreases the positive predictive value of fecal immunochemical tests for colorectal cancer but does not affect their sensitivity. J Pers Med 2021; 11: 497
• 17 Vandenbroucke JP, von Elm E, Altman DG. et al. Strengthening the reporting of observational studies in epidemiology (STROBE): explanation and elaboration. PLoS Med 2007; 4: e297
• 18 Thomsen MK, Njor SH, Rasmussen M. et al. Validity of data in the Danish colorectal cancer screening database. Clin Epidemiol 2017; 9: 105-111
• 19 Gislason GH, Rasmussen JN, Abildstrøm SZ. et al. Long-term compliance with beta-blockers, angiotensin-converting enzyme inhibitors, and statins after acute myocardial infarction. Eur Heart J 2006; 27: 1153-1158
• 20 Lamberts M, Lip GYH, Hansen ML. et al. Relation of nonsteroidal anti-inflammatory drugs to serious bleeding and thromboembolism risk in patients with atrial fibrillation receiving antithrombotic therapy. Ann Intern Med 2014; 161: 690
• 21 MedicinMacro. Available at (Accessed 22.11.2022): https://github.com/tagteam/heaven
• 22 Quan H, Sundararajan V, Halfon P. et al. Coding algorithms for defining comorbidities in ICD-9-CM and ICD-10 administrative data. Med Care 2005; 43: 1130-1139
• 23 Landefeld CS, Beyth RJ. Anticoagulant-related bleeding: Clinical epidemiology, prediction, and prevention. Am J Med 1993; 95: 315-328
• 24 Barada K, Abdul-Baki H, El Hajj II. et al. Gastrointestinal bleeding in the setting of anticoagulation and antiplatelet therapy. J Clin Gastroenterol 2009; 43: 5-12
• 25 Clemens A, Strack A, Noack H. et al. Anticoagulant-related gastrointestinal bleeding—could this facilitate early detection of benign or malignant gastrointestinal lesions?. Ann Med 2014; 46: 672-678
• 26 Hong KS, Kim YK, Bae HJ. et al. Quality of anticoagulation with warfarin in Korean patients with atrial fibrillation and prior stroke: a multicenter retrospective observational study. J Clin Neurol 2017; 13: 273
• 27 Løkkegaard T, Pedersen TH, Lind B. et al. Good quality of oral anticoagulation treatment in general practice using international normalised ratio point of care testing. Dan Med J 2015; 62: A5010
• 28 Martin J, Halm EA, Tiro JA. et al. Reasons for lack of diagnostic colonoscopy after positive result on fecal immunochemical test in a safety-net health system. Am J Med 2017; 130: 93.e1-93.e7
• 29 Fisher DA, Jeffreys A, Coffman CJ. et al. Barriers to full colon evaluation for a positive fecal occult blood test. Cancer Epidemiol Biomarkers Prev 2006; 15: 1232-1235
• 30 Carlson CM, Kirby KA, Casadei MA. et al. Lack of follow-up after fecal occult blood testing in older adults: Inappropriate screening or failure to follow up?. Arch Intern Med 2011; 171: 249-256
• 31 Crotta S, Segnan N, Paganin S. et al. High rate of advanced adenoma detection in 4 rounds of colorectal cancer screening with the fecal immunochemical test. Clin Gastroenterol Hepatol 2012; 10: 633-638
• 32 van der Vlugt M, Grobbee EJ, Bossuyt PM. et al. Adherence to colorectal cancer screening: four rounds of faecal immunochemical test-based screening. Br J Cancer 2017; 116: 44-49
• 33 Hsu W-F, Chang C-Y, Chang C-C. et al. Risk of colonoscopy-related complications in a fecal immunochemical test-based population colorectal cancer screening program. Endoscopy 2022; 54: 290-298
• 34 Rasmussen SL, Krarup HB, Sunesen KG. et al. Hypermethylated DNA as a biomarker for colorectal cancer: a systematic review. Colorectal Dis 2016; 18: 549-561