Benefit–Risk Assessment of Rivaroxaban in Older Patients With Nonvalvular Atrial Fibrillation or Venous Thromboembolism

Fig. 1. Rate differences (95% CI) per 10,000 PYs of rivaroxaban versus warfarin for efficacy and safety outcomes in patients with NVAF (ROCKET-AF, safety/on-treatment analysis set). CI confidence interval; CNS central nervous system; MI myocardial infarction; NMCR nonmajor clinically relevant; NVAF nonvalvular atrial fibrillation; PY patient-year. The primary efficacy outcome is the composite of stroke and non-CNS systemic embolism. The major secondary efficacy outcome 1 is the composite of stroke, non-CNS systemic embolism, and vascular death (includes deaths due to spontaneous bleeding, MI, stroke, heart failure, and arrhythmias). The major secondary efficacy outcome 2 is the composite of stroke, non-CNS systemic embolism, MI, and vascular death. The principal safety outcome is the composite of major bleeding and NMCR bleeding. Fatal bleeding requires that the death be adjudicated as vascular

Fig. 2. NCB* incidence differences (95% CI) per 10,000 PYs (ROCKET-AF, safety/on-treatment analysis set) or per 10,000 patients (EINSTEIN DVT/PE and Extension, ITT analysis set; EINSTEIN CHOICE, full analysis set) for rivaroxaban versus comparators in patients with NVAF and VTE, overall and by age subgroups. CI confidence interval; CNS central nervous system; DVT deep vein thrombosis; ITT intention-to-treat; MI myocardial infarction; NCB net clinical benefit; NVAF nonvalvular atrial fibrillation; PE pulmonary embolism; PY patient-year; VTE venous thromboembolism. *NCB for NVAF (ROCKET-AF) is the composite of vascular death, stroke, MI, fatal bleeding, critical organ bleeding, and non-CNS systemic embolism; NCB for VTE (EINSTEIN studies) is the composite of symptomatic recurrent DVT, nonfatal or fatal PE, and major bleeding

Fig. 3. Cumulative excess number of primary events versus major bleeding based on the Kaplan–Meier method, on treatment up to day 1140, in patients aged ≥ 65 years in the ROCKET-AF study (safety/on-treatment analysis set). On-treatment was the period between the date of the first double‐blind study medication to the date of the last double‐blind study medication administration plus 2 days. Efficacy and major bleeding were from randomization to first event; fatal (narrow definition) or critical organ bleeding was from first dose to first event. Negative values favor rivaroxaban, and positive values favor warfarin

Fig. 4. Risk differences (95% CI) per 10,000 patients based on Kaplan–Meier cumulative incidences at Day 185 with rivaroxaban versus enoxaparin/VKA for efficacy and safety outcomes in patients with VTE (pooled EINSTEIN DVT and EINSTEIN PE, ITT analysis set). DVT deep vein thrombosis; ITT intention-to-treat; NMCR nonmajor clinically relevant; PE pulmonary embolism; VKA vitamin K antagonist; VTE venous thromboembolism. The primary efficacy outcome is the composite of symptomatic recurrent DVT and nonfatal or fatal PE. The secondary efficacy outcome is the composite of symptomatic recurrent DVT, nonfatal or fatal PE, and all-cause mortality. The principal safety outcome is the composite of major bleeding and NMCR bleeding

Fig. 5. Kaplan–Meier cumulative incidence difference of primary efficacy outcome events (symptomatic recurrent VTE) prevented and safety outcome events (ISTH major bleeding) caused, comparing rivaroxaban versus enoxaparin/VKA in patients aged ≥ 65 years (pooled EINSTEIN DVT and EINSTEIN PE, ITT analysis set). DVT deep vein thrombosis; ISTH International Society on Thrombosis and Haemostasis; ITT intention-to-treat; PE pulmonary embolism; VKA vitamin K antagonist, VTE venous thromboembolism. The x axis of the Kaplan–Meier figures is restricted to the period in which ≥ 10% of the analysis set subjects are at risk, as suggested by Pocock SJ, Clayton TC, Altman DG. Lancet. 2002;359:1686–1689

Fig. 6. Risk differences (95% CI) per 10,000 patients based on Kaplan–Meier cumulative incidences at day 185 with rivaroxaban versus placebo for efficacy and safety outcomes in patients with extended VTE treatment (EINSTEIN Extension, ITT analysis set). DVT deep vein thrombosis; ITT intention-to-treat; NMCR nonmajor clinically relevant; PE pulmonary embolism; VTE venous thromboembolism. The primary efficacy outcome is the composite of symptomatic recurrent DVT and nonfatal or fatal PE. The secondary efficacy outcome is the composite of symptomatic recurrent DVT, nonfatal or fatal PE, and all-cause mortality. The principal safety outcome is major bleeding

Fig. 7. Kaplan–Meier cumulative incidence difference of primary efficacy outcome events (symptomatic recurrent VTE) prevented and safety outcome events (ISTH major bleeding) caused, comparing rivaroxaban versus placebo (EINSTEIN Extension, ITT analysis set) in patients aged ≥ 65 years. ISTH International Society on Thrombosis and Haemostasis; ITT intention-to-treat; VTE venous thromboembolism. The x axis of the Kaplan–Meier figures is restricted to the period in which ≥ 10% of the analysis set subjects are at risk, as suggested by Pocock S.J., Clayton T.C., Altman D.G. Lancet. 2002;359:1686–1689

Fig. 8. Risk differences (95% CI) per 10,000 patients based on Kaplan–Meier cumulative incidences at 1 year with rivaroxaban versus aspirin for efficacy and safety outcomes in patients with extended VTE treatment (EINSTEIN CHOICE, full analysis set). The primary efficacy outcome is the composite of symptomatic recurrent nonfatal or fatal venous thromboembolism. The principal safety outcome is major bleeding

Fig. 9. Kaplan–Meier cumulative incidence difference of primary efficacy outcome events (symptomatic recurrent VTE) prevented and safety outcome events (ISTH major bleeding) caused, comparing (A) rivaroxaban 20 mg and (B) rivaroxaban 10 mg versus aspirin (EINSTEIN CHOICE, full analysis set) in patients aged ≥ 65 years. ISTH International Society on Thrombosis and Haemostasis; VTE venous thromboembolism. The x axis of the Kaplan–Meier figures is restricted to the period in which ≥ 10% of the analysis set subjects are at risk, as suggested by Pocock S.J., Clayton T.C., Altman D.G. Lancet. 2002;359:1686–1689