Rivaroxaban to Reduce the Risk of Major

Venous and Arterial Thrombotic Events,

Hospitalization and Death in Medically Ill
Outpatients with COVID-19: Primary results of
the PREVENT-HD Randomized Clinical Trial
Gregory Piazza, Alex Spyropoulos, Judith A. Hsia,
Mark Goldin, William Towner, Alan S. Go, Todd M. Bull,
Stephen Weng, Concetta Lipardi, Elliot S. Barnathan
and Marc P. Bonaca

Rivaroxaban is not currently indicated for the treatment or prevention of thrombotic events in patients with COVID-19. Please refer to your local
guidelines before prescription.
MA-M_RIV-ALL-1338-1
PREVENT-HD Investigated the Efficacy and Safety of Rivaroxaban for Prevention
of Major Thrombotic Events and Death in Hospitalized Patients with COVID-19

◆ Patients with COVID-19 are at risk of major thrombotic events

◆ Rivaroxaban was shown to reduce the risk of cardiovascular events versus standard of
Background
care after hospitalization for COVID-19 in patients with increased thrombotic risk and low
bleeding risk2

◆ To evaluate the efficacy and safety of rivaroxaban in outpatients with symptomatic

Study aim COVID-19 and at least one additional risk factor for thrombosis

◆ Study type: Pragmatic, phase III, double blind, placebo-controlled, randomized clinical trial
◆ Population: Adult patients with acute symptomatic COVID-19 and at least one risk factor
for thrombosis and low bleeding risk
◆ Treatment: Rivaroxaban 10 mg od or placebo
Methods
◆ Study procedures: Performed remotely with no in-person visits
◆ Primary efficacy outcome: First occurrence of the composite of symptomatic VTE, MI,
ischaemic stroke, ALI, non-CNS SE, all-cause hospitalization or death up to day 35
◆ Principal safety endpoint: ISTH critical site or fatal bleeding

1. Capell WH et al. Am Heart J 2021;235:12–23. 2. Ramacciotti E et al. Lancet 2022;399:50–59.

The Evolution of the COVID-19 Pandemic Led to Enrolment
Ending Early in PREVENT-HD
◆ The event incidence was lower than expected (3.2%, 41 events; 8.5% or 333
events required*)
• Vaccination and increasing use of effective COVID-19 treatments contributed to
decreasing death and hospitalization
• The proportion of cases caused by new SARS-CoV-2 variants associated with less
severe complications increased
◆ Enrolling enough patients to reach the required number of events became
unlikely to be feasible
• The number of COVID-19 cases was waning
• More COVID-19 medications precluding concomitant rivaroxaban treatment were
being used
• Only 1284 patients were enrolled (4000 required)

*Required to achieve 90% power to detect a 30% reduction in the primary efficacy endpoint with a two-sided significance level of 5%. The primary efficacy endpoint was the time to the first occurrence of the composite of symptomatic VTE, MI,
ischaemic stroke, ALI, non-CNS SE, all-cause hospitalization or death.
1. Piazza G et al. AHA. Chicago, IL, USA, 5–7 November 2022, Oral LBS.07. [Link] [accessed 9 November 2022]. 2. Capell WH et al. Am Heart J 2021;235:12–23.
PREVENT-HD Enrolled a Population with COVID-19 and a Range of
Thrombotic Risk Factors
Baseline characteristics Rivaroxaban Placebo Thrombotic risk Rivaroxaban Placebo
(n=641) (n=643) factors,* % (n=641) (n=643)
Age, median ± SD 56.3 ± 13.1 55.7 ± 13.3 Aged ≥60 years 49.5 51.5
Female sex, % 62.2 59.7 BMI ≥35 kg/m2 40.4 42.5
Diabetes requiring 22.0 20.7
BMI, kg/m2, median ± SD 32.6 ± 7.9 33.1 ± 8.1
medication
Current or former smoker, 35.8 31.6 Cancer 11.9 13.2
%
CAD 5.6 5.1
Days after positive
COVID-19 test, % VTE 5.0 4.8
Thrombophilia 3.3 2.0
1–5 days 50.2 49.9
CVD or ischaemic 1.4 1.4
6–14 days 49.8 50.1 stroke
Vaccinated vs 2.5 1.7 PAD 1.4 1.2
COVID-19, % Heart failure 1.4 1.2
Aspirin at baseline, % 17.2 17.7 D-dimer > ULN# 0.8 0.9
*Patients were required to have at least one of the risk factors listed.
#Within 2 weeks of COVID-19 test.

Piazza G et al. AHA. Chicago, USA, 5–7 November 2022, Oral LBS.07. [Link] [accessed 9 November 2022].
Rivaroxaban Reduced Thrombotic Events, but not Primary Efficacy
Outcome Events, Versus Placebo

Primary efficacy outcome* and Primary efficacy outcome* and

components (ITT, N=1284) components (mITT,# N=1197)
Placebo Rivaroxaban Placebo Rivaroxaban

4 4
3.4 3.3
proportion (%)

proportion (%)
3.0
3 2.6 3 2.7
Incidence

Incidence
2.5
2.0 1.8
2 2

1 0.5 1
0.3 0.3 0.3 0.3 0.3 0.2 0.2
0.0 0.0 0.0 0.0
0 hospitalization 0

hospitalization
VTE

VTE
outcome*

outcome*
Ischaemic

Ischaemic
Death

Death
Primary

Primary
efficacy

efficacy
stroke

stroke
All-cause

All-cause
*Time to the first occurrence of the composite of symptomatic VTE, MI, ischaemic stroke, ALI, non-CNS SE, all-cause hospitalization or death.
#Randomized participants who took at least one dose of study intervention.

Piazza G et al. AHA. Chicago, IL, USA, 5–7 November 2022, Oral LBS.07. [Link] [accessed 9 November 2022].
 The Risk of Bleeding was Low and Consistent with the Safety Profile
of Rivaroxaban

Safety outcomes (safety analysis set) PREVENT-HD was not

Placebo Rivaroxaban powered to detect definitive
4
p=0.01 differences between treatment
groups.#
proportion (%)

3 2.8
Incidence

p=0.01

2
1.5
The PREVENT-HD study does
not support routine
1 0.8
anticoagulation in
0.2 0.2
0
0.0 0.0 0.0 non-hospitalized patients with
COVID-19.
bleeding

bleeding
critical site

ISTH major
bleeding*

NMCR

Trivial
Fatal or

bleeding

*Principal safety endpoint.

#Enrolment was ended early; fewer patients than planned were enrolled and event rates were lower than expected.

Piazza G et al. AHA. Chicago, USA, 5–7 November 2022, Oral LBS.07. [Link] [accessed 9 November 2022].