INVICTUS
Trial question
Is rivaroxaban noninferior to VKA in patients with rheumatic heart disease-associated AF?
Study design
Multi-center
Open label
RCT
Population
Characteristics of study participants
72.0% female
28.0% male
N = 4531
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 VKA (dose adjustment to maintain an INR of 2.0-3.0).
Primary outcome
Incidence of composite outcome of stroke, systemic embolism, MI, or death from vascular or unknown causes
8.21%/yr
6.49%/yr
8.2 %/yr
6.2 %/yr
4.1 %/yr
2.1 %/yr
0.0 %/yr
Rivaroxaban
Vitamin K
antagonist
Difference exceeding
non-inferiority
margin ✗
Difference exceeding non-inferiority margin in the incidence of composite outcome of stroke, systemic embolism, MI, 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
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).
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 VKA with respect to the incidence of composite outcome of stroke, systemic embolism, MI, 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.
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