MICHELLE TRIAL -RIVAROXABAN

VERSUS NO ANTICOAGULATION
FOR POST-DISCHARGE
THROMBOPROPHYLAXIS AFTER
HOSPITALISATION FOR COVID-19

Presenter: Dr. Vikas Kumar Mall

INTRODUCTION
 More thrombotic events in Covid 19 than ARDS
associated with other diseases.
 Cytokine storm and immune dysregulation leads to
activation of coagulation cascade.
 Anticoagulation during hospital stay is standard of
care in severe Covid.
 Post-discharge patients with COVID-19 show
incidences of symptomatic VTE ranging from 1.5 to
2·5%.
 Open-label, Multicentre, Randomised trial conducted at
14 centre in brazil.
 COVID-19 patients at increased risk for VTE with
[IMPROVE] score of ≥4
or
 Score 2-3 with a D-dimer >500 ng/mL

 Randomly assigned (1:1) to receive, at hospital

discharge, Rivaroxaban 10 mg/day or no
anticoagulation for 35 days.
 Funding Bayer

 Science Valley Research Institute (São Paulo, Brazil)

was responsible for data and site management and all
statistical analysis
 The largest prospective registry
 Included 4906 post-discharge patients with COVID-
19
 Incidence of the primary endpoint of venous
thromboembolism, arterial thromboembolism, or all-
cause death was 7·13%.
 46% lower in patients prescribed post-discharge
prophylactic anticoagulation.
 STUDY DESIGN
 Pragmatic, open-label (with blinded adjudication),
Multicentre, Randomised, controlled trial.
Inclusion criteria
 ≥18 years of age

 Hospitalized for minimum of 3 days with COVID-19

infection
 On standard-dose Thromboprophylaxis

 Total modified Improve venous thromboembolism (VTE)

Risk Score ≥4
 or

 2 or 3 and D-dimer >500 ng/ml

EXCLUSION CRITERIA
 Any bleeding within the last 3 months
 Surgery, biopsy, or trauma within the last 4 weeks or
planned
 Required anticoagulation after discharge

 Use of dual antiplatelet therapy during hospitalization

 Chronic kidney disease

 PROCEDURES
 Randomized at discharge.

 Sample size- 320 patients.

 Study drug started within the first 24 h after hospital discharge.

 Maintained for 35 days.

 During follow up- detailed assessment of chest pain, dyspnoea,

peripheral oedema, pain in the lower limbs, pulse evaluation, and
signs of bleeding.
 FOLLOW UP
Two follow up visits
 On day 7

 On day 35

 Bilateral lower limb venous Doppler ultrasound and CTPA

were performed.
 PRIMARY EFFICACY OUTCOMES
 Primary efficacy outcome- composite of symptomatic/fatal VTE.

 Asymptomatic VTE detected by Doppler ultrasound and CT

 Arterial thromboembolism (MI, stroke, and major adverse limb

event) and cardiovascular death at day 35.

 The primary safety outcome- major bleeding, defined according

to the International Society on Thrombosis and Haemostasis
(ISTH) criteria.
 SECONDARY EFFICACY OUTCOME
 Combination of symptomatic or fatal VTE.

 Composite of symptomatic VTE or all-cause mortality.

 Composite of symptomatic VTE, MI, Non-haemorrhagic

stroke, or CV death.

 The secondary safety outcomes- combination of major,

clinically relevant non-major, and other bleeding,
according to ISTH criteria.
 RESULT
 Efficacy analyses were done using the intention-to-treat principle.

 Primary efficacy outcome at day 35.

Rivaroxaban group- 5 (3·14%) of 159 patients

 control group -15 (9·43%) of 159 patients primary efficacy outcome event

(RR 0·33, 95% CI 0·13–0·90; p=0·0293)

 Yielding a relative risk reduction of 67%

 The primary efficacy outcome was driven mainly by pulmonary embolism in

the control group
 Primary efficacy and safety outcomes.
 The primary endpoint was a composite of symptomatic or
fatal VTE, asymptomatic VTE detected BY B/L Lower
limb USG and CTPA, symptomatic arterial thrombosis
and cardiovascular death at day 35.
 SECONDARY EFFICACY OUTCOME
 Symptomatic and fatal VTE-
 Rivaroxaban group - 1 (0·63%) of 159 pts. control group
8 (5·03%) of 159 pts.
(RR 0·13, 95% CI 0·02–0·99; p=0·0487).

 Symptomatic VTE and all-cause mortality

 Rivaroxaban group- 4 (2·52%) of 159 pts.

 Control group- 9 (5·66%) of 159 pts.

(RR 0·44, 95% CI 0·14–1·41; p=0·1696)

SUBGROUP ANALYSIS
 DISCUSSION
 Extended post-discharge thromboprophylaxis with
rivaroxaban 10 mg/day for 35 days , when compared with
no anticoagulation, resulted in better clinical outcome.

 Treatment group has-

 Lower number of events.

 More asymptomatic events.

LIMITATION
 Open-label design has a potential risk of bias.

 Not every patient received CT pulmonary angiogram.

 Higher number of imaging evaluations occurred in those

patients receiving anticoagulation.

 CTPA could not diffentiate embolism and

immunomediated primary pulmonary arterial thrombosis.