PHRI’s COMPASS Long Term Open Label Extension (LTOLE) “further highlights and supports long-term use of [Factor Xa inhibitor anticoagulant] rivaroxaban, plus aspirin for vascular protection in patients at high risk of cardiovascular events,” says PHRI Senior Scientist John Eikelboom, a principal investigator on COMPASS and COMPASS LTOLE.
Xarelto (brand name of rivaroxaban) plus aspirin is a form of therapy known as dual path inhibition (DPI) which is widely approved by healthcare authorities for use in patients with increased vascular risk and coronary artery disease, peripheral artery disease, or both.
Of the patients originally randomized in COMPASS – the largest clinical study (2017, NEJM) of rivaroxaban – 12,964 participants were subsequently enrolled in the open-label extension at 455 sites in 32 countries.
COMPASS LTOLE patients received the vascular dose of Xarelto plus aspirin for a median of 374 days. They were followed every 6 months to evaluate adherence and safety, and to collect clinical outcomes, including stroke, MI, and mortality.
In COMPASS LTOLE patients with chronic CAD and/or PAD, extended combination treatment for a median of 1 year and a maximum of 3 years was associated with incidence rates for efficacy and bleeding that were similar to, or lower than, those seen during the randomized treatment phase, without any new safety signals, Eikelboom and his coauthors – including PHRI’s Jackie Bosch, Stuart Connolly, Jessica Tyrwhitt, Shrikant Bangdiwala, Darryl Leong, Eva Lonn, Sonia Anand, Andre Lamy, Mukul Sharma, and Salim Yusuf – recently published these findings in European Heart Journal CV Pharmacotherapy.
Comparison with XATAO registry
Outside the context of a randomized trial, clinical characteristics of patients at risk, bleeding rates, and clinical event rates in patients receiving DPI were unknown – until the XATOA registry, revealing that patients at high risk of vascular disease are being prioritized for DPI therapy in clinical practice.
In the XATOA registry, rates of major adverse cardiovascular events (MACE) were similar to these in the COMPASS trial; rates of major adverse limb events (MALE) were higher, consistent with the greater proportion of patients with PAD in the study.
“Major bleeding rates were even lower than in COMPASS. The findings give us additional evidence of the benefits of using DPI in patients at high risk of vascular disease, and should be considered as a treatment option,” says the University of Edinburgh’s Keith Fox, principal investigator of XATOA.
Fox’s co-authors on the publication, “Patients selected for dual pathway inhibition in clinical practice have similar characteristics and outcomes to those included in the COMPASS randomized trial: The XATOA Registry” include PHRI’s Jackie Bosch and Sonia Anand.