6/28/23, 11:37 PM INVICTUS Pathway Feedback Search Clinical Topics Home Studies INVICTUS INVICTUS Disease Atrial fibrillation Trial question Is rivaroxaban noninferior to vitamin K antagonist in patients with rheumatic heart disease- associated AF? Study design Multi-center Open label RCT Population Characteristics of study participants 72.0% female N = 4531 28.0% male 4531 patients (3274 female, 1257 male) Inclusion criteria: patients with AF and echocardiographically documented rheumatic heart disease Key exclusion criteria: mechanical heart valve; dual antiplatelet therapy; treatment with dual strong inhibitors of CYP3A4 and P-glycoprotein; severe renal insufficiency; pregnancy Interventions N=2275 rivaroxaban (at a dose of 15-20 mg/day depending upon CrCl) N=2256 vitamin K antagonist (dose adjustment to maintain an INR of 2.0-3.0) Primary outcome Incidence of composite outcome of stroke, systemic embolism, myocardial infarction, or death from vascular or unknown causes 8.2 %/yr 8.21 https://web.pathway.md/studies/reczdsRqRM8ZuYYO5 1/2 6/28/23, 11:37 PM INVICTUS Pathway 6.49 6.2 %/yr 4.1 %/yr Difference exceeding nonferiority margin 2.1 %/yr 0.0 %/yr Rivaroxaban Vitamin K antagonist Difference exceeding nonferiority margin in the incidence of composite outcome of stroke, systemic embolism, myocardial infarction, or death from vascular or unknown causes (8.21 percent / y vs. 6.49 percent / y; HR 1.25, 95% CI 1.1 to 1.41) Secondary outcomes Borderline significant increase in the incidence of stroke (1.32 percent / y vs. 0.94 percent / y; HR 1.37, 95% CI 1 to 1.89) No significant difference in the incidence of systemic embolism (0.09 percent / y vs. 0.14 percent / y; HR 0.59, 95% CI 0.22 to 1.63) Borderline significant increase in the incidence of death from any cause (7.95 percent / y vs. 6.35 percent / y; HR 1.23, 95% CI 1.09 to 1.4) Safety outcomes No significant difference in major bleeding. Significant difference in fatal bleeding (0.07% vs. 0.22%). Conclusion In patients with AF and echocardiographically documented rheumatic heart disease, rivaroxaban was not noninferior to vitamin K antagonist with respect to the incidence of composite outcome of stroke, systemic embolism, myocardial infarction, or death from vascular or unknown causes. Reference Stuart J Connolly, Ganesan Karthikeyan, Mpiko Ntsekhe et al. Rivaroxaban in Rheumatic Heart Disease-Associated Atrial Fibrillation. N Engl J Med. 2022 Sep 15;387(11):978-988. Open reference URL https://web.pathway.md/studies/reczdsRqRM8ZuYYO5 2/2