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1st Journal Reading

Rivaroxaban or Aspirin for Extended Treatment


of Venous Thromboembolism

dr. Selly Cintya Gusman

Department of Internal Medicine


Dr. M. Djamil Hospital Padang
Medical Faculty of Andalas University
2017
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Background
pulmonary
embolism

The third
Venous most
thrombo common
embolism cause of
vascular death

deep-vein
thrombosis

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The mainstay of treatment is anticoagulation

in patients without active cancer, guidelines suggest the


use of direct oral anticoagulant agents such as
rivaroxaban over vitamin K antagonists such as warfarin
for 3 months or longer

patients with venous thromboembolism are at increased


risk for arterial thrombotic events, including myocardial
infarction, stroke, and vascular death

Attempts to reduce the risk of bleeding when treatment


is extended include the use of lower-dose anticoagulant
therapy and the use of aspirin in place of an
anticoagulant agent
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the Reduced-dosed Rivaroxaban in the Long-
term Prevention of Recurrent Symptomatic
Venous Thromboembolism (EINSTEIN
CHOICE) trial

compared the efficacy and safety of these two doses of


rivaroxaban with those of aspirin in patients with venous
thromboembolism who had completed 6 to 12 months of
anticoagulation therapy and for whom there was equipoise
regarding the need for continued anticoagulation.
determine whether the lower dose of rivaroxaban was as
effective as the higher dose and whether it was associated with
less bleeding

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Patients with venous thromboembolism
require extended treatment

full-intensity lower-intensity
anticoagulation anticoagulation aspirin
therapy therapy

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METHODS

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Study Design and Oversight
double-
blind

comparing the
efficacy and safety of
two doses of
rivaroxaban with phase 3
randomized
those of aspirin for study
the extended
treatment of venous
thromboembolism

1 year after
the initial 6
to 12
months of
7 therapy
Patients
eligible for
ineligible
inclusion
had a contraindication to continued
18 years of age or older
anticoagulant therapy

had objectively confirmed, symptomatic required extended anticoagulant therapy


proximal deep-vein thrombosis or at therapeutic doses or antiplatelet
pulmonary embolism therapy

had been treated for 6 to 12 months with creatinine clearance of < 30 ml per
an anticoagulant agent minute

had not interrupted therapy for more than hepatic disease associated with a
7 days before randomization coagulopathy

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Randomization

The intended
duration of
administration of
Patients were the study drug was
assigned, in a 1:1:1 12 months
ratio, to receive 20
mg of rivaroxaban,
10 mg of
rivaroxaban, or 100
Patients were mg of aspirin, all
enrolled at least 24 given once daily with
hours after they had food
received the last dose
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of a direct oral
anticoagulant agent
Outcome Measures

efficacy safety
outcome outcome
primary : recurrent fatal or
nonfatal pulmonary
embolism, deep-vein
The principal : major
thrombosis and unexplained
bleeding
death for which pulmonary
embolism could not be
ruled out

Others : myocardial Other : clinically relevant


infarction, ischemic stroke, nonmajor bleeding, a
systemic embolism, venous composite of major or
thrombosis in locations clinically relevant nonmajor
other than the deep veins of bleeding, and nonmajor
the lower limbs, and death bleeding that led to study-
from any cause drug interruption for more
10 than 14 days
Surveillance and Follow-up

Patients underwent assessment at days


30, 90, 180, 270, and 360 and at 30
days after stopping the study
medication

All the patients who stopped a study


treatment earlier than scheduled were
followed until the end of the intended
treatment period

Patients were instructed to report to


the study center if they had symptoms
suggestive of recurrent venous
thromboembolism or bleeding

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Statistical Analysis
Efficacy and safety outcomes were analyzed with the use of a Cox
proportional hazards model, stratified according to the index
diagnosis (deep-vein thrombosis or pulmonary embolism).

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RESULT

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Study Patients

From March 2014


exclusion of 31 patients
through March 2016, a 3365 patients were
(0.9%) because they did
total of 3396 patients included in the primary
not receive any study
from 244 sites in 31 analyses
drug
countries were enrolled

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s

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DISCUSSION
Clinical strategies for extended anticoagulation in patients with
venous thromboembolism are uncertain

Previous studies compared with placebo, aspirin reduced the


relative risk of recurrent venous thromboembolism by 32% ,
whereas a 20-mg dose of rivaroxaban reduced the relative risk
by 82%

This study shows that as compared with aspirin, both the 20-mg
and 10-mg doses of rivaroxaban reduced the relative risk of
recurrent venous thromboembolism by about 70%

Rivaroxaban was more effective than aspirin for the prevention


of recurrent venous thromboembolism and was associated with a
similar risk of bleeding
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Potential limitations of this study

patients who required extended Not powered to show the


treatment with therapeutic doses of therapy was given for up
noninferiority of the 10-mg dose
anticoagulant agents were excluded to 12 months. of rivaroxaban to the established
treatment regimen of 20 mg

unknown whether the 10-mg additional studies are needed any conclusions with respect
dose of rivaroxaban would be to determine the utility of to this issue are speculative
sufficient to prevent continuing treatment for
recurrence in such patients longer periods

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Rivaroxaban, at both a treatment dose
(20 mg) and a thromboprophylactic
dose (10 mg), was more effective than
aspirin for the prevention of recurrent
venous thromboembolism among
patients who were in equipoise for
continued anticoagulation

The lower risk of a recurrent event


among the patients who received
rivaroxaban was associated with a rate
of bleeding similar to that with aspirin

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THE QUESTION (PICO) OF THE STUDY
Population/ Patients with venous thromboembolism
Problem

Intervention receive once-daily rivaroxaban (at doses of 20 mg or 10 mg)

Comparison receive once-daily 100 mg of aspirin

Outcome The primary efficacy outcome was symptomatic recurrent


fatal or nonfatal venous thromboembolism
The principal safety outcome was major bleeding

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CRITICAL APPRAISAL
Are the Results Valid? Yes Cant Tell No
Was representative sample of patientsassembled at a
early point in thecourse of their disease?

Was the follow-up of these patients sufficientlylong


and complete?
Were outcome criteria either objective or applied in a
blind fashion?
If subgroups with different prognoses are identified,
did adjustment for important prognostic factors take
place?
Was there validation in the other group ofpatients?
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Was this valid result clinically important?

How likely are the outcome event(s) The risk of a recurrent event was
over a specified period of time? significantly lower with rivaroxaban at
either a treatment dose (20 mg) or a
prophylactic dose (10 mg) than with
aspirin, without a significant increase in
bleeding rates

How precise are the prognostic Hazard ratio for 20 mg of rivaroxaban vs.
estimates? aspirin, 0.34; 95% confidence interval [CI],
0.20 to 0.59;
Hazard ratio for 10 mg of rivaroxaban vs.
aspirin, 0.26; 95% CI, 0.14 to 0.47;
P<0.001 for both comparisons
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Can I apply this valid, important Yes Cant tell No
evidence about prognosis to my
patient?

Were the study patients similar to


our patient

Will this evidence make a clinically


important impact on my
conclusions about what to offer to
tell my patients

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