NOAC plus aspirin reduces CV events in stable CAD and/or PAD patients with and without diabetes

The Role Of Combination Antiplatelet And Anticoagulation Therapy In Diabetes And Cardiovascular Disease: Insights From The Compass Trial

Presented at ACC.20 by Deepak Bhatt, MD (Boston, MA, USA)

Introduction and methods

Patients with CAD or PAD and diabetes are at high risk of CV events. One potential way to address residual CV risk is dual pathway inhibition (DPI), which combines antiplatelet therapy with anticoagulation therapy.

This pre-specified analysis of the COMPASS trial specifically examined the effect of DPI in 6,922 patients with diabetes at baseline and 11,356 patients without diabetes. All patients had stable CAD and/or PAD. Patients were randomly assigned to receive either low-dose rivaroxaban (2.5mg twice daily) plus aspirin (100mg daily) or placebo plus aspirin (100mg daily).

The primary efficacy endpoint was CV death, MI or stroke. Secondary efficacy endpoints consisted of all-cause mortality and the composite endpoint of CV Death, MI, Stroke, MALE, or major vascular amputation. The primary safety endpoint was modified ISTH criteria -major bleeding. The prespecified net clinical benefit consisted of CV death, MI, stroke, fatal bleeding, and symptomatic bleeding into a critical organ.

Main results

• For the primary endpoint, a significant risk reduction was found in the rivaroxaban plus aspirin arm compared with the aspirin alone arm in patients with and without diabetes (HR 0.74, 95%CI 0.61-0.90, P=0.002, ARR 2.3% for patients with diabetes, and HR 0.77, 95%CI 0.64-0.93, P=0.005, ARR 1.4% for those without diabetes). The P value for interaction was 0.77 and was therefore not significant, indicating that the benefits of rivaroxaban plus aspirin were similar and consistent in patients with and without diabetes.

• The secondary efficacy endpoints of all-cause mortality and the composite endpoint were also reduced in the rivaroxaban plus aspirin arm compared to the aspirin alone arm in patients with and without diabetes, with a non-significant finding for all-cause mortality in those without diabetes (all-cause death: HR 0.81, 95%CI 0.65-1.00, P=0.05, ARR 1.9% for patients with diabetes, and HR 0.84, 95%CI 0.68-1.03, P=0.09, ARR 0.6% for those without diabetes, P-interaction=0.82; Composite endpoint: HR 0.73, 95%CI 0.61-0.88, p=0.0007, ARR 2.7% for those with diabetes, and HR 0.74, 95%CI 0.62-0.89, p=0.001, ARR 1.7% for those without diabetes, P-interaction=0.88).

• A significant increase in major bleeding was observed in the rivaroxaban plus aspirin arm vs. the aspirin alone arm in patients with and without diabetes (HR 1.69, 95%CI 1.33-2.15, P<0.0001 for those with diabetes, and HR 1.70, 95%CI 1.25-2.31, P=0.0006 for those without diabetes, P-interaction=0.97). No significant differences were found between treatment groups in risk for intracranial bleeding or fatal bleeding in patients with and without diabetes.

• A reduction in net clinical benefit was found in the rivaroxaban plus aspirin arm compared to the aspirin alone arm in patients with or without diabetes (HR 0.78, 95%CI 0.65-0.94, P=0.02, ARR 2.7% for those with diabetes, and HR 0.81, 95%CI 0.68-0.97, P=0.01, ARR 1.0% for those without diabetes).

Conclusion

Low-dose rivaroxaban plus aspirin reduced the primary endpoint in patients with CAD and/or PAD, irrespective of the presence or absence of diabetes, compared to aspirin alone. The absolute risk reductions were numerically larger is patients with diabetes compared to those without diabetes. A significant increase in major bleeding was observed in the low-dose rivaroxaban plus aspirin arm compared to the aspirin alone arm for those with and without diabetes, but no difference between treatment arms was found for intracranial or fatal bleeding. The net clinical benefit was reduced in the rivaroxaban plus aspirin arm in patients with and without diabetes, and was numerically greater in those with diabetes.

- Our coverage of ACC.20 is based on the information provided during the congress –

The results were published simultaneously in Circulation Watch the video by prof. Bhatt