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Major Bleeding in Patients With Coronary or Peripheral Artery Disease Treated With Rivaroxaban Plus Aspirin
John W Eikelboom1, Jacqueline J Bosch2, Stuart J Connolly1
1Hamilton Health Sciences, Hamilton, Ontario, Canada; McMaster University, Hamilton, Ontario, Canada; Population Health Research Institute, Hamilton, Ontario, Canada.
Insights
The combination of rivaroxaban and aspirin in patients with coronary or peripheral artery disease increased major bleeding events, primarily from the gastrointestinal tract, though most were mild to moderate and manageable.
Area of Science:
- Cardiovascular Medicine
- Pharmacology
Background:
- Patients with coronary or peripheral artery disease often face risks of major adverse cardiovascular events and mortality.
- The combination of rivaroxaban and aspirin has shown potential in reducing these events but may increase bleeding risk.
Purpose of the Study:
- To explore the effects of rivaroxaban plus aspirin versus aspirin alone on the characteristics of bleeding events.
- Investigate the sites, timing, severity, and management of bleeding in the COMPASS study.
Main Methods:
- Analysis of bleeding data from the COMPASS study involving patients with coronary or peripheral artery disease.
- Comparison of bleeding rates, sites, timing, and management between the rivaroxaban plus aspirin group and the aspirin alone group.
Main Results:
- The combination therapy significantly increased modified ISTH major bleeding, ISTH major bleeding, and minor bleeding compared to aspirin alone.
- The gastrointestinal tract was the most common site for increased major bleeding, predominantly occurring within the first year.
- Most bleeding episodes were mild to moderate in intensity and managed with supportive therapy; transfusion rates were also higher with combination therapy.
Conclusions:
- Combination therapy with rivaroxaban and aspirin increases major bleeding, particularly gastrointestinal bleeding, in patients with established cardiovascular disease.
- The majority of excess bleeding events were mild to moderate, occurred within the first year, and were managed conventionally.
Background:
In patients with coronary or peripheral artery disease, the combination of rivaroxaban 2.5 mg twice daily and aspirin 100 mg once daily compared with aspirin 100 mg once daily reduced major adverse cardiovascular events and mortality and increased bleeding.
Objectives:
This study sought to explore the effects of the combination of rivaroxaban and aspirin compared with aspirin on sites, timing, severity, and management of bleeding in the COMPASS (Cardiovascular Outcomes for People Using Anticoagulation Strategies) study.
Methods:
This study reports, by treatment group, the number and proportion of patients; hazard rate ratios for bleeding according to site and severity; the timing of bleeding using landmark analyses; and the number and proportion of patients who received blood products and other hemostatic treatments.
Results:
Of 27,395 patients enrolled (mean age 68 years, 22% women), 18,278 were randomized to the combination of rivaroxaban and aspirin or to aspirin alone and followed for a mean of 23 months. Compared with aspirin alone, the combination increased modified International Society on Thrombosis and Hemostasis major bleeding (288 of 9,152 [3.1%] vs. 170 of 9,126 [1.9%]), (HR: 1.70; 95% CI: 1.40 to 2.05; p < 0.001), International Society on Thrombosis and Hemostasis major bleeding (206 of 9,152 [2.3%] vs. 116 of 9,126 [1.3%]), (HR: 1.78; 95% CI: 1.41 to 2.23; p < 0.0001), and minor bleeding (838 of 9,152 [9.2%] vs. 503 of 9,126 [5.5%]), (HR: 1.70; 95% CI 1.52 to 1.90; p < 0.0001); the combination also increased the need for any red cell transfusion (87 of 9,152 [1.0%] vs. 44 of 9,126 [0.5%]), (HR: 1.97; 95% CI 1.37 to 2.83, p = 0.0002). The gastrointestinal (GI) tract was the most common site of increased major bleeding (140 of 9,152 [1.5%] vs. 65 of 9,126 [0.7%]), (HR: 2.15; 95% CI: 1.60 to 2.89; p < 0.001), and the increase in bleeding was predominantly in the first year after randomization. Approximately one-third of major GI bleeding was gastric or duodenal, one-third was colonic or rectal, and one-third was from an unknown GI site. The study investigators reported that approximately three-quarters of major bleeding episodes were of mild or moderate intensity. A similar proportion of patients in each treatment group who experienced major bleeding received platelets, clotting factors, or other hemostatic agents.
Conclusions:
The combination of rivaroxaban and aspirin compared with aspirin alone increased major bleeding, mainly from the GI tract. Most excess bleeding occurred during the first year after randomization, was of mild or moderate intensity, and was managed with conventional supportive therapy. (Rivaroxaban for the Prevention of Major Cardiovascular Events in Coronary or Peripheral Artery Disease [COMPASS]; NCT01776424).
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