Rivaroxaban antithrombotics

Description Results

death 0.67 [0.53; 0.86]

cardiovascular death 0.66 [0.51; 0.85]

Cardiovascular death, MI, or stroke 0.83 [0.72; 0.96]

major bleeding 3.43 [2.06; 5.71]

ISTH major or clinically relevant nonmajor bleeding 1.75 [1.52; 2.01]

any bleeding 1.75 [1.52; 2.01]

major or minor bleeding 1.75 [1.52; 2.01]

fatal bleeding 0.67 [0.24; 1.88]

MI 0.90 [0.74; 1.08]

death 0.42 [0.33; 0.53]

cardiovascular death 0.42 [0.33; 0.53]

MI 0.53 [0.45; 0.63]

Cardiovascular death, MI, or stroke 0.50 [0.44; 0.57]

major bleeding 4.33 [2.63; 7.12]

ISTH major or clinically relevant nonmajor bleeding 2.27 [1.98; 2.59]

any bleeding 2.27 [1.98; 2.59]

coronary events 0.91 [0.58; 1.41]

fatal bleeding 1.67 [0.73; 3.82]

major bleeding 17.64 [2.34; 132.76]

ISTH major or clinically relevant nonmajor bleeding 3.36 [2.21; 5.10]

Cardiovascular death, MI, or stroke 0.63 [0.39; 1.01]

major bleeding 3.76 [0.24; 59.88]

Cardiovascular death, MI, or stroke 0.52 [0.23; 1.19]

death, MI, stroke, recurrent ischaemia 0.60 [0.29; 1.25]

ISTH major or clinically relevant nonmajor bleeding 1.71 [0.76; 3.85]

rivaroxaban 2.5 mg twice daily in addition to standard care (n=5174)

vs.

placebo (n=5176)

3 arms: rivaroxaban (2.5 mg twice daily or 5 mg twice daily) in addition to standard care and placebo

double blind

Parallel groups

Sample size: 5174/5176

Primary endpoint: CV death, MI, stroke

FU duration: 13 months

rivaroxaban 5 mg twice daily in addition to standard care (n=5176)

vs.

placebo (n=5176)

3 arms: rivaroxaban (2.5 mg twice daily or 5 mg twice daily) in addition to standard care and placebo

double blind

Sample size: 5176/5176

Primary endpoint: CV death, MI, stroke

FU duration: 13 months

rivaroxaban 5 mg twice daily (n=519)

vs.

placebo (n=1160)

dose finding study: rivaroxaban 5 mg, 10 mg, or 20 mg once daily, 2.5 mg, 5 mg, or 10 mg twice daily and placebo

double blind

Parallel groups

Sample size: 519/1160

Primary endpoint: clinically significant bleeding

FU duration: 6 months

dose-finding study

rivaroxaban 2.5 mg twice daily (n=152)

vs.

placebo (n=1160)

dose finding study: rivaroxaban 5 mg, 10 mg, or 20 mg once daily, 2.5 mg, 5 mg, or 10 mg twice daily and placebo

double blind

Sample size: 152/1160

Primary endpoint: clinically significant bleeding

FU duration: 6 months

dose-finding study

all stroke or systemic embolism or death 0.85 [0.74; 0.97]

haemorragic stroke(or intracerebral hemorrhage) 0.58 [0.38; 0.89]

fatal bleeding 0.50 [0.31; 0.80]

intracranial hemorrhage(hemorrhagic stroke+hematomas) 0.67 [0.47; 0.95]

Life threatening major bleeding 0.69 [0.53; 0.89]

Gastrointestinal major bleeding 1.46 [1.19; 1.78]

non vascular death 0.94 [0.75; 1.18]

vascular death,TIA,nonfatal stroke or systemic embolism 0.94 [0.84; 1.05]

all death 0.92 [0.82; 1.03]

coronary events 0.80 [0.62; 1.04]

vascular death 0.94 [0.81; 1.09]

major bleeding 1.04 [0.90; 1.20]

fatal stroke(ischemic+hemorrhagic) 0.70 [0.49; 1.02]

thrombo-embolic event (cerebral or systemic) 0.88 [0.75; 1.04]

ischemic stroke 0.99 [0.82; 1.20]

All stroke(ischemic+hemorrhagic/fatal+non fatal) 0.84 [0.69; 1.01]

myocardial infarction 0.91 [0.72; 1.16]

major and clinically relevant non-major bleeding 1.03 [0.96; 1.11]

systemic thrombo-embolic complication 0.74 [0.42; 1.31]

thromboembolic event(cerebral or systemic) 0.98 [0.80; 1.19]

thromboembolic event*(TE event or ischemic stroke or systemic thromboembolic event) 0.98 [0.80; 1.19]

Rivaroxaban 20mg p.o. once daily (n=7131)

vs.

Warfarin p.o. once daily titrated to a target INR of 2.5 (range 2.0 to 3.0, inclusive) (n=7133)

double blind

Parallel groups

Sample size: 7131/7133

Primary endpoint: stroke or non-CNS systemic embolism

FU duration: median 1.94 y

rivaroxaban (n=3892)

vs.

warfarin INR 2-3 (n=3875)

double-blind

Parallel groups

Sample size: 3892/3875

Primary endpoint:

FU duration:

major bleeding 17.00 [6.50; 44.44]

CV events 76.00 [66.58; 86.75]

all causes deaths 82.00 [70.52; 95.35]

CV death (IHD+stroke) 78.00 [63.69; 95.53]

fatal stroke 78.00 [63.69; 95.53]

ischemic stroke 51.00 [38.12; 68.22]

all stroke 58.00 [44.13; 76.23]

Rivaroxaban 2.5 mg twice daily alone (n=27400)

vs.

aspirin 100 mg once daily (n=0)

3 arms rivaroxaban and aspirin, rivaroxaban alone, aspirin alone

Sample size: 27400/0

Primary endpoint:

FU duration:

rivaroxaban (2.5 mg twice daily) plus aspirin (100 mg once daily) (n=9152)

vs.

aspirin 100 mg once daily (n=9126)

3 arms rivaroxaban and aspirin, rivaroxaban alone, aspirin alone

double-blind

Parallel groups

Sample size: 9152/9126

Primary endpoint: cardiovascular death, stroke, MI

FU duration: 23 months

death 0.98 [0.87; 1.10]

rivaroxaban at a dose of 2.5 mg twice daily (n=2507)

vs.

placebo (n=2515)

Sample size: 2507/2515

Primary endpoint: death all cause, MI, stroke

FU duration: 21.1 months

rivaroxaban (at a daily dose of 15 mg) (n=3609)

vs.

aspirin (at a daily dose of 100 mg) (n=3604)

Sample size: 3609/3604

Primary endpoint: first recurrence of ischemic or hemorrhagic stroke or systemic embolism

FU duration:

rivaroxaban (15 mg twice daily for 3 weeks, followed by 20 mg once daily) for 3, 6, or 12 months (n=2419)

vs.

standard therapy with enoxaparin followed by an adjusted-dose vitamin K antagonist (n=2413)

open

Parallel groups

Sample size: 2419/2413

Primary endpoint: symptomatic recurrent venous thromboembolism

FU duration: 9.8 months

DVT (asymptomatic or symptomatic) 0.42 [0.22; 0.79]

distal DVT 0.36 [0.17; 0.73]

total VTE and all-cause mortality 0.42 [0.22; 0.79]

proximal DVT 0.95 [0.20; 4.59]

non-fatal PE NaN [NaN; NaN]

major bleeding 0.00 [0.00; NaN]

DVT (asymptomatic or symptomatic) 0.23 [0.12; 0.43]

proximal DVT 0.03 [0.00; 0.23]

total VTE and all-cause mortality 0.30 [0.18; 0.51]

major VTE (fatal and non fatal DVT,PE) 0.12 [0.04; 0.34]

death 0.98 [0.24; 3.90]

coronary events 0.49 [0.12; 1.95]

major bleeding 3.02 [0.61; 14.95]

distal DVT 0.49 [0.24; 1.00]

non-fatal PE 3.91 [0.44; 34.92]

Symptomatic venous thromboembolism 0.55 [0.20; 1.48]

DVT (asymptomatic or symptomatic) 0.20 [0.11; 0.35]

proximal DVT 0.11 [0.05; 0.29]

distal DVT 0.34 [0.16; 0.71]

total VTE and all-cause mortality 0.21 [0.13; 0.35]

Symptomatic venous thromboembolism 0.20 [0.06; 0.69]

major VTE (fatal and non fatal DVT,PE) 0.12 [0.05; 0.28]

death 0.34 [0.07; 1.66]

coronary events 1.33 [0.30; 5.95]

major bleeding 1.00 [0.06; 15.98]

non-fatal PE 0.25 [0.03; 2.25]

major or clinically relevant non-major bleeding 1.20 [0.93; 1.54]

DVT (asymptomatic or symptomatic) 0.53 [0.41; 0.68]

distal DVT 0.53 [0.41; 0.70]

total VTE and all-cause mortality 0.51 [0.39; 0.65]

Symptomatic venous thromboembolism 0.34 [0.15; 0.75]

major VTE (fatal and non fatal DVT,PE) 0.38 [0.18; 0.82]

death 0.00 [0.00; NaN]

coronary events 0.51 [0.05; 5.59]

major bleeding 1.19 [0.40; 3.53]

myocardial infarction 0.51 [0.05; 5.61]

proximal DVT 0.48 [0.22; 1.05]

non-fatal PE 0.00 [0.00; NaN]

proximal DVT 0.23 [0.07; 0.80]

total VTE and all-cause mortality 0.69 [0.51; 0.92]

death 0.66 [0.11; 3.94]

coronary events 0.33 [0.03; 3.16]

major bleeding 2.47 [0.78; 7.86]

myocardial infarction 0.20 [0.02; 1.69]

distal DVT 0.82 [0.57; 1.17]

non-fatal PE 0.49 [0.15; 1.64]

asymptomatic DVT 0.72 [0.51; 1.01]

Symptomatic venous thromboembolism 0.60 [0.29; 1.27]

major VTE (fatal and non fatal DVT,PE) 0.59 [0.30; 1.16]

symptomatic DVT 0.60 [0.22; 1.63]

major or clinically relevant non-major bleeding 1.34 [0.86; 2.07]

Symptomatic deep vein thrombosis during follow-up 0.44 [0.22; 0.88]

Venous thromboembolism or death 0.73 [0.54; 0.98]

Clinically relevant bleeding 1.66 [1.17; 2.35]

All-cause death during follow-up 0.80 [0.58; 1.10]

Major bleeding during follow-up 1.88 [0.84; 4.22]

VTE 0.76 [0.52; 1.10]

rivaroxaban 10mg daily for 5–9 days (n=142)

vs.

once-daily subcutaneous enoxaparin dose of 40 mg for 5–9 days (n=157)

dose finding study (doses of 5, 10, 20, 30, or 40 mg)

double blind

Parallel groups

Sample size: 142/157

Primary endpoint: any DVT, PE, all cause death

FU duration: 5-9 days

BAY 59-7939 5mg b.i.d. for 5–9 days (n=102)

vs.

enoxaparin 30 mg b.i.d. for 5–9 days (n=105)

dose ranging study with doses 2.5, 5, 10, 20, and 30 mg

double blind

Parallel groups

Sample size: 102/105

Primary endpoint:

FU duration: 5-9 days

rivaroxaban 10mg once daily for 35 days (n=2266)

vs.

enoxaparin 40mg subcutaneous once daily for 31-39 days (n=2275)

double blind

Parallel groups

Sample size: 2266/2275

Primary endpoint: DVT, PE, death

FU duration: 36 days (range 30-42)

extended thromboprophylaxis with rivaroxaban 10mg once daily for 31-39 days (n=1252)

vs.

enoxaparin 40mg subcutaneous once daily for 10-14 days (n=1257)

double blind

Parallel groups

Sample size: 1252/1257

Primary endpoint: DVT, PE , all cause death

FU duration: 30-42 days

rivaroxaban 10 mg once daily for 10- 14 days (n=1254)

vs.

enoxaparin 40 mg subcutaneous once daily for 10-14 days (n=1277)

double blind

Parallel groups

Sample size: 1254/1277

Primary endpoint: DVT, PE all cause mortality

FU duration: 13-17 days

rivaroxaban 10mg once daily for 10 to 14 days (n=1584)

vs.

enoxaparin 30 mg twice daily by subcutaneous injection for 10-14 days (n=1564)

double blind

Parallel groups

Sample size: 1584/1564

Primary endpoint: total VTE events

FU duration: 40 days

once-daily rivaroxaban at a dose of 10 mg (with the dose adjusted for renal insufficiency) , begun at hospital discharge and continued for 45 days (n=6007)

vs.

placebo (n=6012)

double blind

Sample size: 6007/6012

Primary endpoint: symptomatic venous thromboembolism or death due to venous thromboembolism

FU duration:

recurrent DVT only 0.50 [0.26; 0.94]

All deaths 0.77 [0.51; 1.17]

coronary events 2.99 [0.60; 14.78]

Major bleeding 0.70 [0.35; 1.38]

non fatal PE 1.10 [0.59; 2.08]

fatal PE ∞ [NaN; ∞]

Symptomatic nonfatal pulmonary embolism 1.10 [0.59; 2.08]

recurrent VTE during treatment 0.70 [0.46; 1.07]

Death related to venous thromboembolism 0.66 [0.19; 2.35]

recurrent VTE 0.70 [0.46; 1.07]

recurrent DVT only 0.16 [0.06; 0.41]

non fatal PE 0.15 [0.03; 0.67]

recurrent VTE 0.19 [0.09; 0.40]

major or clinically relevant nonmajor bleeding 5.07 [2.28; 11.31]

death 0.49 [0.04; 5.43]

All deaths 0.49 [0.04; 5.43]

Major bleeding ∞ [NaN; ∞]

fatal PE 0.00 [0.00; NaN]

Death related to venous thromboembolism 0.99 [0.06; 15.74]

recurrent VTE 0.43 [0.19; 0.98]

all bleeding 3.76 [1.63; 8.68]

Major hemorrhage 1.83 [0.68; 4.94]

recurrent venous thromboembolism or major bleeding 0.54 [0.33; 0.89]

Major hemorrhage 0.42 [0.18; 0.98]

All-cause mortality 0.93 [0.64; 1.35]

all bleeding 0.80 [0.54; 1.19]

recurrent VTE 0.67 [0.35; 1.29]

rivaroxaban 20, 30, or 40 mg once daily (n=-9)

vs.

low-molecular-weight heparin followed by vitamin K antagonists (n=-9)

open

Sample size: -9/-9

Primary endpoint:

FU duration:

rivaroxaban 15 mg twice daily for 3 weeks, then 20 mg daily (n=1731)

vs.

enoxaparin 1 mg/kg twice daily >=5 days, then warfarin with target INR between 2-3 (n=1718)

treatment duration (3, 6, or 12 months) decided by physicians. treatment duration of 6 months in 63%, 3 mo in 12% and 12 mo in 25%

open (assessor-blind)

Parallel groups

Sample size: 1731/1718

Primary endpoint: Symptomatic recurrent VTE

FU duration:

rivaroxaban (15 mg twice daily for 3 weeks, followed by 20 mg once daily) for 3, 6, or 12 months (n=2419)

vs.

standard therapy with enoxaparin followed by an adjusted-dose vitamin K antagonist (n=2413)

open

Parallel groups

Sample size: 2419/2413

Primary endpoint: symptomatic recurrent venous thromboembolism

FU duration: 9.8 months

rivaroxaban 20 mg once-daily for an additional 6 or 12 months (n=602)

vs.

placebo (n=595)

double blind

Parallel groups

Sample size: 602/595

Primary endpoint: symptomatic recurrent VTE

FU duration:

rivaroxaban (15 mg twice daily for 3 weeks, then 20 mg once daily for a total of 6 months) (n=203)

vs.

dalteparin (200 IU/kg daily during month 1, then 150 IU/kg daily for months 2-6) (n=203)

open-design

Sample size: 203/203

Primary endpoint:

FU duration:

pilot trial

rivaroxaban (15 mg twice daily for 21 days, followed by 20 mg once daily (n=354)

vs.

(enoxaparin1·0 mg/kg twice daily and warfarin or acenocoumarol; international normalised ratio 2·0–3·0 (n=301)

Sample size: 354/301

Primary endpoint:

FU duration:

sub group analysis