Bleeding on Low-Dose Antithrombotic Therapy a ‘Red Flag’ for New Cancers

Patients with atherosclerosis on antithrombotic drugs who report gastrointestinal or genitourinary bleeding are at a substantially higher risk for new cancer diagnoses in those organ systems compared to those without bleeding, according to a subanalysis of the COMPASS trial.

“These data indicate that gastrointestinal and genitourinary bleeding in patients receiving antithrombotic drugs should prompt a careful search for undiagnosed cancer, even when the bleeding is minor,” write lead author John Eikelboom, MBBS (Population Health Research Institute, Hamilton, Canada), and colleagues.

The analysis, published last week in Circulation, showed that among the more than 27,000 patients from COMPASS, those who reported GI and genitourinary bleeding over a mean follow-up period of 23 months were 20 and 32 times more likely to be diagnosed with cancer, respectively. Notably, randomization to rivaroxaban (Xarelto; Bayer/Janssen) 2.5-mg twice-daily plus low-dose aspirin compared to aspirin alone did not increase the frequency of new cancer diagnosis or of cancer-related mortality.

The findings make “perfect sense,” according to Luke Laffin, MD (Cleveland Clinic, OH), who was not associated with the study. “If we have a malignancy in the GI tract or the genitourinary tract, it's going to be vascular and so it's more likely to bleed,” he explained to TCTMD. “So if we're putting people on medications like low-dose systemic anticoagulation, which the COMPASS trial did, then there is going to be that propensity to bleed.”

Because of this, Laffin encouraged physicians to come out of their respective “silos” and work together as a patient care team. “It's important that we reach across those divisions to try and really address these issues,” he said. “Can we put systems in place to identify and get those patients referred earlier if they do have bleeding in this setting?”

Richard Becker, MD (University of Cincinnati College of Medicine, OH), also commenting on the study for TCTMD, agreed, noting that this kind of bleeding should be a “red flag” for physicians.

“The low frequency of bleeding underscores the importance of routine cancer screening practices as recommended by many national organizations,” he said. “Bleeding among patients taking an anticoagulant with or without a platelet inhibitor should not be used as a surrogate or ‘cancer stress test’ for cancer detection. Patients and providers must work closely with one another to assure optimal health.”

GI, Genitourinary Bleeding

Overall, 9.8% of the COMPASS population experienced major or minor bleeding, of whom 9.9% were subsequently diagnosed with cancer over the 23-month follow-up period.

GI bleeding was linked with a more than 20-fold higher risk of a new GI cancer diagnosis (7.4% vs 0.5%; HR 20.6; 95% CI 15.2-27.8) and a 1.7-fold higher risk of a new non-GI cancer diagnosis (3.8% vs 3.1%; HR 1.7; 95% CI 1.2-2.4) compared with those with no GI bleeding.

The pattern was similar for those who reported genitourinary bleeding, with a more than 32 times higher risk for genitourinary cancer (15.8% vs 0.8%; HR 32.5; 95% CI 24.7-42.9) but no added hazard for nongenitourinary cancer. For urinary bleeding specifically, an almost 100-fold hazard was seen for a new urinary cancer diagnosis (14.2% vs 0.2%; HR 98.5; 95% CI 68.0-142.7).

Put together, GI or genitourinary bleeding led to a 14 times higher risk of a new GI or genitourinary cancer diagnosis (11.4% vs 1.3%; HR 13.8; 95% CI 11.3-16.8) and a 1.5 times higher risk of a new cancer diagnosis that was not GI or genitourinary in nature (2.3% vs 2.1%; HR 1.46; 95% CI 1.01-2.12).

Patients who reported bleeding that was not GI or genitourinary had slightly higher risks of a new cancer diagnosis that was (2.3% vs 1.7%; HR 1.61; 95% CI 1.13-2.29) or was not (4.4% vs 1.93%; HR 3.02; 95% CI 2.32-3.91) GI or genitourinary in nature.

“Our finding that the majority of cancers diagnosed in patients with prior bleeding were diagnosed after ‘any’ (ie, major or minor) bleeding rather than after major bleeding highlights the potential for minor bleeding to unmask new cancers,” Eikelboom and colleagues write. Less than one-third of all new cancers diagnosed after bleeding were diagnosed in patients with prior major bleeding and an even lower proportion of all new gastrointestinal, genitourinary and urinary cancers diagnosed after bleeding were diagnosed in patients with prior major bleeding involving these sites.”

Notably, the researchers did not observe a survival benefit among patients with bleeding who were ultimately diagnosed with cancer, but this is likely because of a limited follow-up period, they say. “Earlier diagnosis of cancer in patients with bleeding might lead to improved outcomes, depending on the site and the stage of cancer at the time of diagnosis.”

Despite the fact that the COMPASS data “haven't been fully embraced by the cardiovascular community yet,” Laffin said, “we're increasingly trying to use low-dose systemic anticoagulation in addition to aspirin in some of these high-risk individuals.” Ultimately, these data speak to the need for a more integrated care model, he stressed. “We just need to be cognizant of [bleeding] as cardiologists and potentially put systems in place to get these patients referred more expediently.”