By Michael H. Crawford, MD
Professor of Medicine, Lucy Stern Chair in Cardiology, University of California, San Francisco
SYNOPSIS: A large Danish registry study showed that in atrial fibrillation patients on oral anticoagulants and who experience a lower gastrointestinal bleed, the incidence of a subsequent diagnosis of colorectal cancer is significantly higher than in those without bleeding.
SOURCE: Rasmussen PV, Dalgaard F, Gislason GH, et al. Gastrointestinal bleeding and the risk of colorectal cancer in anticoagulated patients with atrial fibrillation. Eur Heart J 2022;43:e38-e44.
It might be possible that overt lower gastrointestinal bleeding (LGIB) in patients taking oral anticoagulants is associated with a worse prognosis because of underlying colorectal cancer (CRC), but there is little information to inform the work-up and management of this population. Investigators analyzed the Danish National Patient Registry and Registry of Medicinal Product Statistics to study this issue.
All patients age 18 to 100 years with atrial fibrillation or flutter (AF) treated with oral anticoagulants (OAC) were identified from 1996 to 2014 and followed through 2015. The authors excluded patients with a prior diagnosis of CRC, lower endoscopy in the two years before OAC initiation, valvular AF, deep venous thrombosis within six months, or hip or knee surgery within five weeks before OAC initiation. The primary endpoint was a diagnosis of CRC. The resulting population consisted of 125,418 patients (median age 73 years; 58% men). Vitamin K antagonists were the OAC in 85% of patients.
There were 2,576 episodes of LGIB, and 140 CRC diagnoses within one year of the LGIB. Bleeding was most common in the month after starting OAC therapy and increased in prevalence with age. The overall risk of LGIB was less than 1% at six months. With LGIB, the one-year risk of CRC was high in all age groups (3.7% if younger than age 65 years, 8.1% if older than age 85 years) and was lower in those without LGIB (0.2% younger than age 65 years, 0.5% older than age 85 years). The relative risk of a diagnosis of CRC after LGIB was 24.2 (95% CI, 14.5-40.4) in those younger than age 65 years and 12.3 (95% CI, 7.9-19.0) in those older than age 85 years. Most cases of CRC were diagnosed within two months of LGIB onset.
The probability of undergoing lower GI endoscopy after LGIB was higher in younger patients (61% younger than age 65 years, and 57% older than age 85 years). Deeper analyses revealed concomitant antiplatelet therapy increased the risk of LGIB, and the mortality rate was higher overall in those with LGIB. The authors concluded the risk of LGIB after initiation of OAC therapy is highest within the first month of therapy. The risk of CRC is significantly higher in the patients with LGIB vs. without and increases with age (4% in the youngest patients and 8% in the oldest patients after LGIB at one year vs. less than 1% in those without LGIB).
COMMENTARY
OAC therapy could be a stress test for discovering CRC. The data from this study seem to support this assertion. Also, the results seem to support the notion this may represent a situation in which CRC is detected earlier than it otherwise would have been, although this was not addressed here.
The observational design and the restriction to the data available in the registries are two limitations. For example, there is no coagulation testing information for patients on vitamin K antagonists and there are no data on therapy adherence. In addition, the incidence of CRC in those without a LGIB is probably underestimated because such patients are less likely to undergo endoscopy. Finally, this was a study of overt LGIB, not a positive test for fecal blood. The authors did not see data in the registry on fecal blood testing for the entire study period.
Of patients with AF on OAC, only 2% experienced a LGIB, which speaks to the overall safety of this therapy. This is even more remarkable when one considers 85% of patients were on vitamin K antagonists, which may carry a higher risk of bleeding than the new direct-acting OACs. Among those with a LGIB, only 5% received a CRC diagnosis within one year. Thus, many endoscopies will need to be performed for a small but important yield. Interestingly, 61% of those younger than age 65 years with a LGIB underwent endoscopy; only 37% of those older than age 80 years did. The reason for this was not addressed here, but it could suggest a more aggressive diagnostic approach may have detected more CRCs. Overall, the authors emphasized clinicians should not dismiss LGIB on OAC as a result of diffuse mucosal oozing intrinsic to this therapy. Instead, we should work up patients for CRC in whom this is appropriate.
A large Danish registry study showed that in atrial fibrillation patients on oral anticoagulants and who experience a lower gastrointestinal bleed, the incidence of a subsequent diagnosis of colorectal cancer is significantly higher than in those without bleeding.
You have reached your article limit for the month. Subscribe now to access this article plus other member-only content.
- Award-winning Medical Content
- Latest Advances & Development in Medicine
- Unbiased Content