Conference Update

Combination antiplatelet and anticoagulation therapy to bring positive outcomes in diabetes and cardiovascular disease

4 months ago, OP Editor

More recently, a strategy of dual pathway antithrombotic therapy with antiplatelet and a reduced dose of anticoagulant has been tested and shown to be effective. The COMPASS trial demonstrated that aspirin plus rivaroxaban 2.5mg twice daily was superior to placebo for the reduction of ischemic events in 27,395 patients with coronary artery disease (CAD) and/or peripheral artery disease (PAD).1 At the virtual ACC20 conference, results from the pre-specified analysis of COMPASS were presented. The use of rivaroxaban plus aspirin versus aspirin alone in patients with cardiovascular (CV) risk with or without diabetes mellitus (DM) at baseline were assessed.1

DM is a commonly occurring major risk amplifier in patients with established atherosclerosis, particularly polyvascular disease. Coexistence of DM and polyvascular disease constitutes a very high-risk to coronary, cerebral and peripheral ischemic events. Although lipid-lowering therapies and glycemia-modifying drugs can help attenuate this risk, DM still contributes to a pro-thrombotic state and residual CV risk. However, antiplatelet therapy, including dual antiplatelet therapy, has been an established therapy across a wide variety of stable atherosclerotic patients in reducing said risk.

The COMPASS trial was a multicenter, double-blind, randomized, placebo-controlled trial of 27,395 patients with a history of CAD and/or PAD. The primary outcome was CV death, myocardial infarction (MI), or stroke. However, the trial was stopped early at the recommendation of the independent data and safety monitoring board due to the overwhelming efficacy of rivaroxaban plus aspirin arm versus the use of aspirin alone.2

The investigators stated, “There was a consistent and similar relative risk reduction for rivaroxaban plus aspirin versus aspirin alone in patients with and without DM for the primary efficacy endpoint and secondary endpoints including mortality.” However, due to their higher baseline risk, patients with DM have the absolute risk reductions appeared larger versus patients without DM.1

Evaluating the totality of ischemic events (CV death, stroke, myocardial infarction, major adverse limb events, or major vascular amputation) at 3 years, those without DM at baseline had a significant reduction to 6.1% from 7.8%. The corresponding rates for those with DM were reduced 9.4% from 12.1%. The absolute risk reductions were 1.7% and 2.7% respectively. When considering all the findings of the trial, there was a significant increase in major bleeding with the dual pathway regimen in the subgroups of patients with and without DM, with a similar degree of risk increase. However, there were no significant increases in intracranial or fatal bleeding.

This pre-specified analysis of COMPASS showed that patients with stable atherosclerosis and concomitant DM who are being treated with rivaroxaban plus aspirin therapy have greater absolute risk reductions in ischemic events than those patients without DM. This greater absolute efficacy occurs without any incremental increase of major bleeding complications in those with DM versus without DM. Thus, the net clinical benefit when examining the irreversible outcomes appears greater in patients with DM. This finding has proven that the use of dual pathway inhibition with aspirin plus low dose rivaroxaban are particularly attractive among this high-risk population.3

  1. Bhatt DL et al. The Role of Combination Antiplatelet and Anticoagulation Therapy in Diabetes and Cardiovascular Disease: Insights from the COMPASS Trial. Circulation. March 2020:CIRCULATIONAHA.120.046448.
  2. Bhatt et al. The Role Of Combination Antiplatelet And Anticoagulation Therapy In Diabetes And Cardiovascular Disease Insights. Accessed April 28, 2020.
  3. Bhatt_COMPASS_FCR_Abstract.pdf. Accessed April 28, 2020.
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