Studies Reinforce Efficacy of Rivaroxaban Plus Aspirin in Patients with Coronary Artery Disease, Peripheral Artery Disease

New findings published in Cardiovascular Pharmacotherapy highlight the efficacy of dual pathway inhibition (DPI) with rivaroxaban (Xarelto) plus aspirin in patients coronary artery disease (CAD) and/or peripheral artery disease (PAD).

The phase 3 COMPASS long-term open label extension (LTOLE) study and the rivaroxaban Xarelto in Combination with Acetylsalicylic Acid (XATOA) registry provide further evidence supporting the role of DPI with the rivaroxaban vascular dose (2.5 mg twice daily plus aspirin 100 mg once daily) in patients with CAD and/or PAD, according to the study investigators.

Results from LTLOE show that continued treatment with rivaroxaban 2.5 mg twice daily plus aspirin 75 to 100 mg once daily for up to 3 years was associated with similar or lower incidence rates for major cardiovascular (CV) events (MACE) and for bleeding than what was observed in the randomized treatment phase.

In the XATOA registry, real-world evidence illustrated the benefit of DPI with the rivaroxaban vascular dose in patients with CAD and/or PAD, according to the study authors.

“What we saw initially in COMPASS, and now again with its long-term open label continuation study, is that dual-pathway inhibition with Xarelto plus aspirin can significantly reduce the underlying thrombotic risk of cardiovascular events in patients with CAD and/or PAD,” said James F. List, MD, PhD, global therapeutic area head, Cardiovascular, Metabolism, and Retina, Janssen Research & Development, LLC, in a press release. “Additionally, through the real-world XATOA registry, we’ve now uncovered, for the first-time, which types of patients are most often selected for and may benefit from dual pathway inhibition. These data provide practical, clinical insights to those who treat these difficult conditions.”

In the COMPASS trial, the rivaroxaban vascular dose reduced the risk of major CV events by 24% in patients with chronic CAD and/or PAD. Among 27,395 patients randomized in the trial, 12,964 were subsequently enrolled in the LTOLE study to evaluate long-term use of rivaroxaban plus aspirin for up to 3 years.

The findings showed that rivaroxaban 2.5 mg twice daily plus aspirin 75 mg to 100 mg once daily was associated with a primary outcome event rate of 2.35, which was similar to what was observed in the randomized treatment phase. Further, major bleeding rates during LTOLE had an incidence rate of 1.01, whereas the randomized phase showed major bleeding rates of 1.67 per 100 patient years.

“When first presented, the COMPASS results represented a real breakthrough in CAD and PAD, as they confirmed the Xarelto vascular dose is effective in helping to prevent the detrimental cardiovascular events that often occur in these patients,” said professor John Eikelboom, MBBS, MSc, McMaster University in Hamilton, Canada, and lead author of the COMPASS and LTOLE studies, in the press release. “It’s extremely reassuring to see that these benefits continue long-term, as observed in our open label extension study.”

The XATOA registry analysis set included 5532 patients with CAD and/or PAD administered at least 1 dose of DPI with rivaroxaban 2.5 mg and aspirin, of whom 72% had CAD, 58.9% had PAD, and 31.6% had both CAD and PAD. The most frequently reported reason for initiating DPI was the presence of existing, worsening, or newly diagnosed risk characteristics.

Major bleeding occurred at a rate of 0.95 compared to 1.7 in the COMPASS trial. Additionally, the rates of MACE and major adverse limb events were higher in the COMPASS trial and consistent with the greater proportion of patients with PAD in the study.

“For the first time, we’ve uncovered which patient characteristics go into a physician’s decision making for prescribing dual-pathway treatment to help reduce the risk of major cardiovascular events,” said professor Keith Fox, MD, MBChB, FRCP, FESC, FMedSci, University of Edinburgh, and lead author of the XATOA registry, in the press release. “In the XATOA registry, patients who received treatment with Xarelto plus aspirin had outcomes consistent with the COMPASS study. These real-world findings help support the use of DPI in patients at increased risk of vascular events.”

REFERENCE

New Data From Two Large Studies Reinforce Effectiveness of Dual Pathway Inhibition (DPI) with XARELTO® (rivaroxaban) Plus Aspirin in Patients with Coronary Artery Disease (CAD) and/or Peripheral Artery Disease (PAD). Johnson and Johnson. May 23, 2022. Accessed May 31, 2022. https://www.jnj.com/new-data-from-two-large-studies-reinforce-effectiveness-of-dual-pathway-inhibition-dpi-with-xarelto-rivaroxaban-plus-aspirin-in-patients-with-coronary-artery-disease-cad-and-or-peripheral-artery-disease-pad