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Bleeding and new cancer diagnosis in patients with atherosclerosis

  • John W. Eikelboom,
  • Stuart J. Connolly,
  • Jacqueline Bosch,
  • Olga Shestakovska,
  • Victor Aboyans,
  • Marco Alings,
  • Sonia S. Anand,
  • Alvaro Avezum,
  • Scott D. Berkowitz,
  • Deepak L. Bhatt,
  • Nancy Cook-Bruns,
  • Camilo Felix,
  • Keith A.A. Fox,
  • Robert G. Hart,
  • Aldo P. Maggioni,
  • Paul Moayyedi,
  • Martin O’Donnell,
  • Lars Rydén,
  • Peter Verhamme,
  • Petr Widimsky,
  • Jun Zhu,
  • Salim Yusuf

Publication: Circulation, Volume 140, Issue 18, September 2020

Background

Patients treated with antithrombotic drugs are at risk of bleeding. Bleeding may be the first manifestation of underlying cancer.

Methods

We examined new cancers diagnosed in relation to gastrointestinal or genitourinary bleeding among patients enrolled in the COMPASS trial (Cardiovascular Outcomes for People Using Anticoagulation Strategies) and determined the hazard of new cancer diagnosis after bleeding at these sites.

Results

Of 27 395 patients enrolled (mean age, 68 years; women, 21%), 2678 (9.8%) experienced any (major or minor) bleeding, 713 (2.6%) experienced major bleeding, and 1084 (4.0%) were diagnosed with cancer during a mean follow-up of 23 months. Among 2678 who experienced bleeding, 257 (9.9%) were subsequently diagnosed with cancer. Gastrointestinal bleeding was associated with a 20-fold higher hazard of new gastrointestinal cancer diagnosis (7.4% versus 0.5%; hazard ratio [HR], 20.6 [95% CI, 15.2–27.8]) and 1.7-fold higher hazard of new nongastrointestinal cancer diagnosis (3.8% versus 3.1%; HR, 1.70 [95% CI, 1.20–2.40]). Genitourinary bleeding was associated with a 32-fold higher hazard of new genitourinary cancer diagnosis (15.8% versus 0.8%; HR, 32.5 [95% CI, 24.7–42.9]), and urinary bleeding was associated with a 98-fold higher hazard of new urinary cancer diagnosis (14.2% versus 0.2%; HR, 98.5; 95% CI, 68.0–142.7). Nongastrointestinal, nongenitourinary bleeding was associated with a 3-fold higher hazard of nongastrointestinal, nongenitourinary cancers (4.4% versus 1.9%; HR, 3.02 [95% CI, 2.32–3.91]).

Conclusions

In patients with atherosclerosis treated with antithrombotic drugs, any gastrointestinal or genitourinary bleeding was associated with higher rates of new cancer diagnosis. Any gastrointestinal or genitourinary bleeding should prompt investigation for cancers at these sites.

Clinical Trial Registration

URL: https://www.clinicaltrials.gov. Unique identifier: NCT01776424.

Commented by Dr. Marco Moschini

Authors evaluated data from the COMPASS trial (Cardiovascular outcomes for people using anticoagulation strategies) and determined the hazard of new cancer diagnosis after bleeding. The primary objective of COMPASS was to determine whether rivaroxaban 2.5 mg twice daily in combination with aspirin 100 mg once daily or rivaroxaban 5 mg twice daily compared with aspirin 100 mg once daily reduced the risk of the primary outcome, a composite of cardiovascular death, stroke or myocardial infarction among patients with chronic coronary artery disease or peripheral artery disease. In total, 27395 patients were randomized from 602 sites in 33 countries. The trial was stopped after a mean follow up of 23 months because of clear evidence of superiority of the combination of rivaroxaban 2.5 mg twice daily and aspirin 100 mg once daily compared with aspirin 100 mg once daily. Authors evaluated all the type of bleeding occurred in patients and performed further diagnostic to evaluate presence of cancer. Of the 27395 patients enrolled, 9.8% (2678) experienced any major or minor bleeding, 2.6% (713) experienced major bleeding. A total of 1084 patients (4.0%) were diagnosed with cancer during a mean follow up of 23 months.  Among 2678 who experienced bleeding, 257 (9.9%) were subsequently diagnosed with cancer. Genitourinary bleeding was associated with a 32-fold higher hazard of new genitourinary cancer diagnosis (15.8% versus 0.8%; HR, 32.5 [95% CI, 24.7-42.9]), and urinary bleeding was associated with a 98-fold higher hazard of new urinary cancer diagnosis (14.2% versus 0.2%; HR, 98.5; 95% CI, 68.0-142.7).

This high-quality data supports the hypothesis that hematuria in patients treated with antithrombotic drugs should not be under evaluated and represents an important aspect. Physicians should offer to these patients an extensive check up to rule out the presence of urogenital cancers. Use of antithrombotic agent might trigger an episode of hematuria in an existing urogenital lesion, further data are required to validate this hypothesis.