In the phase III COMPASS study, Bayer’s Factor Xa inhibitor, rivaroxaban (Xarelto) vascular dose, 2.5 mg twice daily, plus aspirin 100 mg once daily reduced the risk of the composite outcome of stroke, cardiovascular (CV) death and heart attack by 24% (relative risk reduction) in patients with chronic coronary artery disease (CAD) or peripheral artery disease (PAD). The study compared this combined approach with aspirin 100 mg once daily alone.

Patients included in the study had already received guideline recommended therapy for hypertension, high cholesterol and diabetes. A 5 mg twice daily dose of rivaroxaban was also investigated but the difference in the primary outcome did not reach statistical significance. Data were revealed during two Hot Line presentations at ESC Congress 2017 in Barcelona, Spain, 26-30 August. The COMPASS findings were simultaneously published in The New England Journal of Medicine.

The benefit shown in the combined efficacy endpoint, major adverse cardiovascular events (MACE), for rivaroxaban 2.5 mg twice daily plus aspirin 100 mg once daily was mainly driven by a significant reduction of stroke (42%) and CV death (22%). The regimen also reduced the risk of heart attack by 14% however this result was not statistically significant. This combination regimen demonstrated a substantial 20% improvement in net clinical benefit, defined as the reduction in stroke, CV death, and heart attack balanced against the most serious bleeding events. The hazard ratio for all-cause mortality was 0.82 (95% CI 0.71-0.96; P=0.01). Bleeding incidence rates were low, and while there was an increase in major bleeding, notably there was no significant increase in fatal or intracranial bleeding. Importantly, in the PAD patient population, the combination of major adverse limb events plus all major amputations of a vascular cause were reduced significantly.

Cardiovascular disease, which includes CAD and PAD, is responsible for approximately 17.7 million deaths every year, representing 31% of all global deaths. Additionally, patients with cardiovascular disease have a reduction in life expectancy of over 7 years. CAD and PAD are caused by atherosclerosis, a chronic, progressive disease which is characterised by a build-up of plaque in the arteries. Patients with these conditions are at risk of thrombotic events which may lead to disability, loss of limb and loss of life.

“CAD and PAD remain a major public health burden. Despite the routine use of guideline-recommended antiplatelet therapy, event rates remain substantial,” said John Eikelboom, Associate Professor, Division of Hematology & Thromboembolism, Department of Medicine, McMaster University, Canada. “These findings for the vascular dose of rivaroxaban are arguably the most significant in antithrombotic therapy in this disease area to date. Once approved, this vascular dose provides us with a major opportunity to change clinical practice and better treat patients.”

“Bayer has a long and successful heritage in cardiology and our medicines have already improved the lives of millions of patients across the world,” said Dr Joerg Moeller, Member of the Executive Committee of Bayer AG's Pharmaceutical Division and Head of Development. “The COMPASS study is the first of its kind; no other NOAC has been studied in this patient population and the magnitude of these results clearly shows the benefit rivaroxaban could bring to patients with CAD or PAD. We will now work with regulatory authorities to make this treatment option available to patients as soon as possible.”

The COMPASS study is the largest clinical study of rivaroxaban to date. The study was stopped approximately one year ahead of schedule due to overwhelming efficacy and Bayer, Janssen and the Population Health Research Institute (PHRI) are working towards offering rivaroxaban to study participants in an open-label extension trial. Rivaroxaban is the only non-vitamin K antagonist oral anticoagulant (NOAC) investigated in secondary prevention for cardiovascular disease in stable / chronic CAD or PAD patients.

COMPASS is part of the extensive evaluation of rivaroxaban which, by the time of completion, will include more than 275,000 patients in clinical trials and real-world studies. In addition to COMPASS, Bayer is investigating rivaroxaban in other studies in the cardiovascular field including VOYAGER PAD and COMMANDER-HF.