CC BY 4.0 · TH Open 2022; 06(03): e257-e266
DOI: 10.1055/s-0042-1755606
Original Article

Venous Thromboembolism and Risk of Cancer in Users of Low-Dose Aspirin: A Danish Population-Based Cohort Study

Gencer Kurt
1   Department of Clinical Epidemiology, Aarhus University Hospital and Aarhus University, Aarhus N, Denmark
,
Dávid Nagy
1   Department of Clinical Epidemiology, Aarhus University Hospital and Aarhus University, Aarhus N, Denmark
,
Frederikke S. Troelsen
1   Department of Clinical Epidemiology, Aarhus University Hospital and Aarhus University, Aarhus N, Denmark
,
Nils Skajaa
1   Department of Clinical Epidemiology, Aarhus University Hospital and Aarhus University, Aarhus N, Denmark
,
Rune Erichsen
1   Department of Clinical Epidemiology, Aarhus University Hospital and Aarhus University, Aarhus N, Denmark
,
Dóra K. Farkas
1   Department of Clinical Epidemiology, Aarhus University Hospital and Aarhus University, Aarhus N, Denmark
,
Henrik T. Sørensen
1   Department of Clinical Epidemiology, Aarhus University Hospital and Aarhus University, Aarhus N, Denmark
› Institutsangaben
Funding Department of Clinical Epidemiology is involved in studies with funding from various companies in the form of research grants to and administered by Aarhus University, Aarhus N, Denmark. None of these studies are related to the present study.

Abstract

Background Aspirin may reduce the risk of cancer, particularly gastrointestinal cancer, and venous thromboembolism (VTE). VTE can be the first symptom of occult cancer, but whether it is also a marker of occult cancer in aspirin users remains unknown. Therefore, we investigated the risk of cancer subsequent to VTE among users of low-dose aspirin.

Methods We conducted a population-based cohort study using data from Danish health registries for the years 2001 to 2018. We identified all patients with a first-time diagnosis of VTE who also redeemed a prescription for low-dose aspirin (75–150mg) within 90 days prior to the first-time VTE. We categorized aspirin users by the number of prescriptions filled as new users (<5 prescriptions), short-term users (5–19 prescriptions), and long-term users (>19 prescriptions). We computed the absolute cancer risks and standardized incidence ratios (SIRs) for cancer using national cancer incidence rates.

Results We followed-up 11,759 users of low-dose aspirin with VTE. Long-term users comprised 50% of aspirin users. The 1-year absolute risk of cancer was 6.0% for new users and 6.7% for short-term and long-term users, with corresponding SIRs of 3.3 (95% confidence interval [CI]: 2.8–4.0), 3.2 (95% CI: 2.9–3.7), and 2.8 (95% CI: 2.6–3.2), respectively. After the first year of follow-up, the SIR decreased to 1.2 (95% CI: 1.1–1.4) for new users, 1.1 (95% CI: 1.1–1.3) for short-term users, and 1.1 (95% CI: 1.0–1.2) for long-term users.

Conclusion VTE may be a harbinger of cancer, even in users of low-dose aspirin, regardless of duration of use.

Supplementary Material



Publikationsverlauf

Eingereicht: 03. März 2022

Angenommen: 04. Juli 2022

Artikel online veröffentlicht:
12. September 2022

© 2022. The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution License, permitting unrestricted use, distribution, and reproduction so long as the original work is properly cited. (https://creativecommons.org/licenses/by/4.0/)

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  • References

  • 1 Heit JA. Epidemiology of venous thromboembolism. Nat Rev Cardiol 2015; 12 (08) 464-474
  • 2 Sørensen HT, Mellemkjaer L, Olsen JH, Baron JA. Prognosis of cancers associated with venous thromboembolism. N Engl J Med 2000; 343 (25) 1846-1850
  • 3 Sørensen HT, Mellemkjaer L, Steffensen FH, Olsen JH, Nielsen GL. The risk of a diagnosis of cancer after primary deep venous thrombosis or pulmonary embolism. N Engl J Med 1998; 338 (17) 1169-1173
  • 4 Baron JA, Gridley G, Weiderpass E, Nyrén O, Linet M. Venous thromboembolism and cancer. Lancet 1998; 351 (9109): 1077-1080
  • 5 Iodice S, Gandini S, Löhr M, Lowenfels AB, Maisonneuve P. Venous thromboembolic events and organ-specific occult cancers: a review and meta-analysis. J Thromb Haemost 2008; 6 (05) 781-788
  • 6 Sørensen HT, Sværke C, Farkas DK. et al. Superficial and deep venous thrombosis, pulmonary embolism and subsequent risk of cancer. Eur J Cancer 2012; 48 (04) 586-593
  • 7 Prandoni P, Lensing AW, Büller HR. et al. Deep-vein thrombosis and the incidence of subsequent symptomatic cancer. N Engl J Med 1992; 327 (16) 1128-1133
  • 8 van Es N, Le Gal G, Otten HM. et al. Screening for occult cancer in patients with unprovoked venous thromboembolism: a systematic review and meta-analysis of individual patient data. Ann Intern Med 2017; 167 (06) 410-417
  • 9 Becattini C, Agnelli G. Aspirin for prevention and treatment of venous thromboembolism. Blood Rev 2014; 28 (03) 103-108
  • 10 Algra AM, Rothwell PM. Effects of regular aspirin on long-term cancer incidence and metastasis: a systematic comparison of evidence from observational studies versus randomised trials. Lancet Oncol 2012; 13 (05) 518-527
  • 11 Friis S, Riis AH, Erichsen R, Baron JA, Sørensen HT. Low-dose aspirin or nonsteroidal anti-inflammatory drug use and colorectal cancer risk: a population-based, case-control study. Ann Intern Med 2015; 163 (05) 347-355
  • 12 Cuzick J, Otto F, Baron JA. et al. Aspirin and non-steroidal anti-inflammatory drugs for cancer prevention: an international consensus statement. Lancet Oncol 2009; 10 (05) 501-507
  • 13 Elwood PC, Gallagher AM, Duthie GG, Mur LAJ, Morgan G. Aspirin, salicylates, and cancer. Lancet 2009; 373 (9671): 1301-1309
  • 14 Antithrombotic Trialists' Collaboration. Collaborative meta-analysis of randomised trials of antiplatelet therapy for prevention of death, myocardial infarction, and stroke in high risk patients. BMJ 2002; 324 (7329): 71-86
  • 15 Sørensen HT, Horvath-Puho E, Søgaard KK. et al. Arterial cardiovascular events, statins, low-dose aspirin and subsequent risk of venous thromboembolism: a population-based case-control study. J Thromb Haemost 2009; 7 (04) 521-528
  • 16 Agnelli G, Becattini C. Venous thromboembolism and atherosclerosis: common denominators or different diseases?. J Thromb Haemost 2006; 4 (09) 1886-1890
  • 17 Schmidt SA, Farkas DK, Pedersen L, Prandoni P, Sørensen HT. Venous thrombosis and risk of cancer in patients with arterial cardiovascular disease. Thromb Res 2015; 135 (01) 96-101
  • 18 Schmidt M, Pedersen L, Sørensen HT. The Danish Civil Registration System as a tool in epidemiology. Eur J Epidemiol 2014; 29 (08) 541-549
  • 19 Schmidt M, Schmidt SA, Sandegaard JL, Ehrenstein V, Pedersen L, Sørensen HT. The Danish National Patient Registry: a review of content, data quality, and research potential. Clin Epidemiol 2015; 7: 449-490
  • 20 Pottegård A, Schmidt SAJ, Wallach-Kildemoes H, Sørensen HT, Hallas J, Schmidt M. Data resource profile: the Danish National Prescription Registry. Int J Epidemiol 2017; 46 (03) 798-798f
  • 21 Gjerstorff ML. The Danish Cancer Registry. Scand J Public Health 2011; 39 (7, suppl): 42-45
  • 22 Schmidt M, Schmidt SAJ, Adelborg K. et al. The Danish health care system and epidemiological research: from health care contacts to database records. Clin Epidemiol 2019; 11: 563-591
  • 23 Schmidt M, Hallas J, Friis S. Potential of prescription registries to capture individual-level use of aspirin and other nonsteroidal anti-inflammatory drugs in Denmark: trends in utilization 1999-2012. Clin Epidemiol 2014; 6: 155-168
  • 24 The Danish Medicines Agency. . MEDICINPRISER.DK. Accessed July 28, 2022, at: https://www.medicinpriser.dk/Default.aspx
  • 25 The Danish Health Data Authority. The yearly cancer report from the Danish Health Data Authority. Accessed November 09, 2021, at: https://sundhedsdatastyrelsen.dk/da/tal-og-analyser/analyser-og-rapporter/sygdomme-og-behandlinger/kraeft/kraeft_nyetilfaelde_aarsrapport
  • 26 Charlson ME, Pompei P, Ales KL, MacKenzie CR. A new method of classifying prognostic comorbidity in longitudinal studies: development and validation. J Chronic Dis 1987; 40 (05) 373-383
  • 27 Thygesen SK, Christiansen CF, Christensen S, Lash TL, Sørensen HT. The predictive value of ICD-10 diagnostic coding used to assess Charlson comorbidity index conditions in the population-based Danish National Registry of Patients. BMC Med Res Methodol 2011; 11: 83
  • 28 American Diabetes Association. 10. Cardiovascular disease and risk management: Standards of Medical Care in Diabetes-2021. Diabetes Care 2021; 44 (Suppl. 01) S125-S150
  • 29 Sørensen HT. Studies on the associations among venous thromboembolism, cancer, arterial cardiovascular events, and mortality [dissertation]. Aalborg, Denmark: Aalborg University; 2021
  • 30 Andersen PK, Geskus RB, de Witte T, Putter H. Competing risks in epidemiology: possibilities and pitfalls. Int J Epidemiol 2012; 41 (03) 861-870
  • 31 Aalen OO, Johansen S. An empirical transition matrix for non-homogeneous markov chains based on censored observations. Scand J Stat 1978; 5 (03) 141-150
  • 32 Breslow NE, Day NE. Statistical methods in cancer research. Volume II–the design and analysis of cohort studies. IARC Sci Publ 1987; (82) 1-406
  • 33 Altman DG. Confidence intervals for the number needed to treat. BMJ 1998; 317 (7168): 1309-1312
  • 34 Bibbins-Domingo K. U.S. Preventive Services Task Force. Aspirin use for the primary prevention of cardiovascular disease and colorectal cancer: U.S. preventive services task force recommendation statement. Ann Intern Med 2016; 164 (12) 836-845
  • 35 Troelsen FS, Farkas DK, Erichsen R, Sørensen HT. Risk of lower gastrointestinal bleeding and colorectal neoplasms following initiation of low-dose aspirin: a Danish population-based cohort study. BMJ Open Gastroenterol 2020; 7 (01) e000453
  • 36 Sundbøll J, Adelborg K, Munch T. et al. Positive predictive value of cardiovascular diagnoses in the Danish National Patient Registry: a validation study. BMJ Open 2016; 6 (11) e012832
  • 37 Johannesdottir SA, Mægbæk ML, Hansen JG, Lash TL, Pedersen L, Ehrenstein V. Correspondence between general practitioner-reported medication use and timing of prescription dispensation. Clin Epidemiol 2012; 4: 13-18
  • 38 Delluc A, Antic D, Lecumberri R, Ay C, Meyer G, Carrier M. Occult cancer screening in patients with venous thromboembolism: guidance from the SSC of the ISTH. J Thromb Haemost 2017; 15 (10) 2076-2079
  • 39 Piccioli A, Lensing AW, Prins MH. et al; SOMIT Investigators Group. Extensive screening for occult malignant disease in idiopathic venous thromboembolism: a prospective randomized clinical trial. J Thromb Haemost 2004; 2 (06) 884-889
  • 40 Carrier M, Lazo-Langner A, Shivakumar S. et al; SOME Investigators. Screening for occult cancer in unprovoked venous thromboembolism. N Engl J Med 2015; 373 (08) 697-704
  • 41 Prandoni P, Bernardi E, Valle FD. et al. Extensive computed tomography versus limited screening for detection of occult cancer in unprovoked venous thromboembolism: a multicenter, controlled, randomized clinical trial. Semin Thromb Hemost 2016; 42 (08) 884-890
  • 42 Prins MH, Lensing AW, Hirsh J. Idiopathic deep venous thrombosis. Is a search for malignant disease justified?. Arch Intern Med 1994; 154 (12) 1310-1312
  • 43 NICE guideline. Venous thromboembolic diseases: diagnosis, management and thrombophilia testing. Accessed November 09, 2021, at: https://www.nice.org.uk/guidance/ng158