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Among patients with stable atherosclerosis, add-on rivaroxaban to aspirin reduced major cardiovascular events compared with aspirin alone, whether or not they had diabetes, according to subgroup analysis results of a phase 3 trial published in Circulation.
The Cardiovascular Outcomes for People Using Anticoagulation Strategies (COMPASS;
ClinicalTrials.gov Identifier: NCT01776424) trial findings supported the use of a combined antithrombotic and antiplatelet treatment, as low-dose rivaroxaban 2.5 mg twice daily was superior to aspirin and placebo for reduction of ischemic events in patients with coronary or peripheral artery disease, in addition to a significant reduction in cardiovascular and all-cause mortality. The goal of the current prespecified analysis of COMPASS was to explore the outcomes of combined treatment with rivaroxaban and aspirin compared with aspirin monotherapy according to diabetes status.
Of 18,278 participants included in the COMPASS trial randomly assigned to the combination of rivaroxaban and aspirin or aspirin alone, 6922 had diabetes at baseline and 11,356 were not previously diagnosed with diabetes.
There was a consistent and similar relative risk reduction in the primary endpoint of cardiovascular mortality, myocardial infarction, or stroke at 3 years among patients treated with rivaroxaban and aspirin compared with aspirin alone, irrespective of diabetes status. The hazard ratio [HR] for the primary outcome with rivaroxaban and aspirin compared with placebo was 0.74 (95% CI, 0.61-0.90; P =.002) in patients with diabetes and 0.77 (95% CI, 0.64-0.93; P =.005) in those without diabetes (P =.77 for interaction).
In patients without diabetes at baseline, there was a significant reduction in total ischemic events (cardiovascular death, stroke, myocardial infarction, major adverse limb events, or major vascular amputation) from 7.8% with aspirin/placebo to 6.1% with aspirin/rivaroxaban. In patients with baseline diabetes, the combined treatment was associated with a reduction from 12.1% to 9.4%.
The researchers noted that while the absolute risk reduction appeared larger in individuals with diabetes (2.7% vs 1.7%), this was likely because of their higher baseline risk. The benefit of the combined treatment was similar in both groups, with an HR of 0.73 (95% CI, 0.61-0.88; P =.0007) in those with diabetes and 0.74 (95% CI, 0.62-0.89; P =.001) in those without diabetes (P =.88 for interaction); the respective numbers needed to treat for 3 years were 38 vs 60 patients.
In a similar fashion, in patients with and without diabetes, there was a similar reduction in all-cause mortality with the combination of rivaroxaban and aspirin compared with aspirin alone (diabetes: HR, 0.81 [95% CI, 0.65-1.00; P =.05]; no diabetes: HR, 0.84 [95% CI, 0.68-1.03; P =.09]; P =.82 for interaction).
There was a significant increase in major bleeding with the combined treatment compared with aspirin alone in the subgroups with and without diabetes, with a similar degree of risk increase. As the bleeding hazards were similar in patients with
vs without diabetes, the absolute net benefit for rivaroxaban appeared particularly favorable in patients with diabetes (2.7% vs 1.0%).
The study had several limitations, including that it was a subgroup analysis with limited power, that diabetes was defined only by case history, and the lack of data on treatment for diabetes, given that it may have had clinical significance. In previous studies, it was reported that there are differences in the beneficial effects of antiplatelets among individuals treated with insulin vs oral medications.
“In patients at acceptable bleeding risk, addition of low-dose rivaroxaban to aspirin should be considered in the secondary prevention regimen of patients with atherosclerosis and diabetes,” recommended the researchers.
Disclosure: This clinical trial was supported by Bayer AG. Please see the original reference for a full list of authors’ disclosures.
Reference
Bhatt DL, Eikelboom JW, Connolly SJ, et al; on behalf of the COMPASS Steering Committee and Investigators. The role of combination antiplatelet and anticoagulation therapy in diabetes and cardiovascular disease: insights from the COMPASS trial [published online March 28, 2020]. Circulation. doi:10.1161/CIRCULATIONAHA.120.046448
