Major bleeding associated with subsequent cancer diagnoses

Bleeding in patients treated with anticoagulants should stimulate a search for cancer, according to late breaking results from the COMPASS trial presented today at ESC Congress 2018.

Professor John Eikelboom, principal investigator, of the Population Health Research Institute, McMaster University, Hamilton, Canada, said: "In patients with stable coronary artery disease or peripheral artery disease, the occurrence of major gastrointestinal bleeding predicts a substantial increase in new gastrointestinal cancer diagnoses, while major genitourinary bleeding predicts a substantial increase in new genitourinary tract cancer diagnoses."

Up to one in ten patients with cardiovascular disease have recurrent events each year. As previously reported, the COMPASS trial found that in patients with coronary artery disease or peripheral artery disease, the combination of rivaroxaban (2.5 mg twice daily) and aspirin reduced cardiovascular events compared to aspirin alone, but there were more major bleeding events in the combined drug group.

For the first time today, the investigators report details on the effect of bleeding on subsequent cancer diagnoses.

Briefly, the trial enrolled 27,395 patients with chronic stable coronary or peripheral artery disease from 602 centres in 33 countries. Patients were randomly allocated to one of three groups: 1) rivaroxaban 2.5 mg twice daily plus aspirin 100 mg once daily 2) rivaroxaban 5 mg twice daily, or 3) aspirin 100 mg once daily. Results in each of the rivaroxaban groups were compared with the aspirin alone group. The mean duration of follow up was 23 months.

The combination increased major bleeding, as defined by the International Society on Thrombosis and Haemostasis (ISTH), compared with aspirin (3.1% versus 1.9%, hazard ratio [HR] 1.70, 95% confidence interval [CI] 1.40-2.05, p<0.0001), but did not significantly increase intracranial (0.3% versus 0.3%, HR 1.16, 95% CI 0.67-2.00, p=0.60) or fatal bleeding (0.2% versus 0.1%, HR 1.49, 95% CI 0.67-3.33, p=0.32).

Major gastrointestinal bleeding was associated with a 20-fold increase in new diagnoses of gastrointestinal cancer (9.3% versus 0.7%, HR 22.6, 95% CI 14.9-34.3, p<0.0001) and a two-fold increase in non-gastrointestinal cancer (4.6% versus 3.1%, HR 2.55, 95% CI 1.47-4.42, p<0.0001).

Major non-gastrointestinal bleeding was associated with a five-fold increase in new non-gastrointestinal cancers (9.4% versus 3.0%, HR 5.49, 95% CI 3.95-7.62, p<0.0001), but not with new gastrointestinal cancer (0.5% versus 0.8%, HR 0.85, 95% CI 0.21-3.45, p=0.82).

Professor Eikelboom said: "More than one in ten patients with major bleeding were subsequently diagnosed with cancer, and more than 20% of new cancer diagnoses were in patients who experienced bleeding. By reducing major cardiovascular events and mortality, the combination of rivaroxaban and aspirin already produces a clear net benefit, and if bleeding unmasks cancer it could potentially lead to the added benefit of improved cancer outcomes."