CARDIOVASCULAR JOURNAL OF AFRICA • Vol 22, No 3, May/June 2011
164
AFRICA
RE-LY trial: new sub-analyses highlight stroke reduction in all
types of non-valvular atrial fibrillation
Two new retrospective sub-analyses
of the RE-LY trial, involving Pradaxa
capsules, suggested that the reduction in
stroke risk achieved with Pradaxa 150
mg over warfarin
1
occurred irrespective
of the CHA
2
DS
2
-VASC risk score
2
and
the type of non-valvular atrial fibrilla-
tion (NVAF) (permanent, persistent and
paroxysmal).
3
The results were presented
at the American College of Cardiology
annual scientific session recently.
2,3
The first sub-analysis assessed the
impact of the novel CHA
2
DS
2
-VASC
risk score,
2
which determines stroke risk
based on age, gender and the presence
of comorbidities,
4
on outcomes in the
RE-LY trial. Patients were grouped into
quartiles based on CHA
2
DS
2
-VASC score
(0–2, 3, 4, 5–9),
2
and results showed that
Pradaxa 150 mg was associated with
reductions in stroke risk compared to
warfarin for all four quartiles (0–2, RR
=
0.63; 3, RR
=
0.61; 4, RR
=
0.53; 5–9, RR
=
0.77; interaction
p
=
0.60).
2
Results of the analysis showed there
was a significant interaction between the
CHA
2
DS
2
-VASC score and rates of major
bleeding, with lower rates for Pradaxa
compared to warfarin for patients in the
first three quartiles, but an increased rate
of major bleeding for the quartile at great-
est risk (0–2, RR
=
0.75; 3, RR
=
0.74; 4,
RR
=
0.83; 5–9, RR
=
1.33; interaction
p
=
0.003).
2
‘This analysis suggests that Pradaxa
150 mg taken twice daily may reduce the
risk of stroke compared to warfarin across
the levels of NVAF-associated stroke
risk, as determined by the CHA
2
DS
2
-
VASC score’, said Paul Reilly, PhD,
clinical programme director, Boehringer
Ingelheim Pharmaceuticals, Inc. ‘These
findings are important because the risk
of stroke in patients with NVAF increas-
es significantly with the presence of
co-morbidities such as diabetes or hyper-
tension.’
Pradaxa was also evaluated in a second
RE-LY sub-analysis, which assessed
efficacy and safety among the 18 107
patients for whom information was avail-
able about the type of NVAF
3
they had:
permanent (long standing), paroxysmal
(arrhythmia terminating spontaneously)
or persistent (lasting beyond seven days).
5
Findings showed that Pradaxa 150 mg
reduced the risk of stroke and systemic
embolism compared to warfarin across
all three subgroups (permanent, HR
=
0.7;
paroxysmal, HR
=
0.61; persistent, HR
=
0.64; interaction
p
=
0.88).
The analysis also showed the follow-
ing rates of major bleeding: permanent
– Pradaxa: 3.07%/yr, warfarin: 2.96%/
yr; paroxysmal – Pradaxa: 3.74%/yr,
warfarin: 3.91%/yr; persistent – Pradaxa:
3.14%/yr, warfarin: 3.88%/yr (interaction
p
=
0.34).
3,6
‘Stroke risk is similar regardless of the
type of non-valvular atrial fibrillation’,
said Greg Flaker, MD and chair of cardio-
vascular research, University of Missouri.
‘These data showed Pradaxa 150 mg
twice daily was associated with lower
rates of stroke than warfarin in patients
with all three types of non-valvular atrial
fibrillation.’
Pradaxa was approved by the USA
Food and Drug Administration in October
2010 to reduce the risk of stroke and
systemic embolism in patients with
NVAF. Pradaxa 150 mg is the only
approved oral anticoagulant that has been
shown to significantly reduce the risk of
stroke, compared to warfarin. Effects of
Pradaxa were more apparent in patients
with lower levels of INR control.
1
Dabigatran was recently recommenda-
tion in an update to the atrial fibrillation
treatment guidelines.
Results from the CHA
2
DS
2
-VASC
sub-analysis
In the sub-analysis, patients were grouped
into quartiles based on the CHA
2
DS
2
-
VASC score (0–2,
n
=
4 042; 3,
n
=
5 365;
4,
n
=
4 374; 5–9,
n
=
4 327). The results
of the sub-analysis showed that Pradaxa
150 mg was associated with reductions in
stroke risk compared to warfarin for all
four quartiles (0–2 – Pradaxa: 0.5%/yr,
warfarin: 0.8%/yr; 3 – Pradaxa: 0.8%/yr,
warfarin: 1.4%/yr; 4 – Pradaxa: 1.0%/yr,
warfarin: 2.0%/yr; 5–9 –Pradaxa: 2.1%/yr,
warfarin: 2.8%/yr; interaction
p
=
0.60).
2
Results of the analysis showed there
was a significant interaction between
CHA
2
DS
2
-VASC score and rates of major
bleeding, with lower rates for Pradaxa 150
mg compared to warfarin for patients in
the first three quartiles, but an increased
rate of major bleeding for the quartile at
greatest risk (0–2 – Pradaxa: 1.8%/yr,
warfarin: 2.4%/yr; 3 – Pradaxa: 2.6%/
yr, warfarin: 3.5%/yr; 4 – Pradaxa: 3.2%/
yr, warfarin: 3.9%/yr; 5–9 – Pradaxa:
5.8%/yr, warfarin: 4.4%/yr; interaction
p
=
0.003).
3
Results from the different types
of NVAF sub-analyses
In the sub-analysis, patients were clas-
sified by the type of NVAF; 6 375 had
permanent NVAF, 5 943 had paroxysmal
NVAF and 5 789 had persistent NVAF.
Results showed that Pradaxa 150 mg
reduced the risk of stroke and systemic
embolism compared to warfarin across all
three subgroups (permanent – Pradaxa:
1.11%/yr, warfarin: 1.58%/yr; paroxysmal
– Pradaxa: 1.09%/yr, warfarin: 1.77%/yr;
persistent – Pradaxa: 1.14%/yr, warfa-
rin: 1.80%/yr; interaction
p
=
0.88).
3,6
Source:
PR Newswire
1.
Pradaxa prescribing information. Ridgefield,
CT: Boehringer Ingelheim Pharmaceuticals,
Inc; March 2011-05-04.
2.
Oldgren J,
et al
. Dabigatran versus warfarin
and impact of CHA2DS2-VASc score on
outcomeinatrialfibrillationpatients:aRE-LY
subgroup analysis. ACC 2011, abstract.
3.
Flaker GC,
et al
. Dabigatran etexilate versus
warfarin in patients with different types of
atrial fibrillation: A RE-LY subgroup analy-
sis. ACC 2011, abstract.
4.
Lip GYH,
et al
. Refining clinical risk strati-
fication for predicting stroke and thrombo-
embolism in atrial fibrillation using a novel
risk factor-based approach: The Euro Heart
Survey on Atrial fibrillation.
Chest
2010;
137
: 263–272.
5.
Fuster V,
et al
. ACC/AHA/ESC 2006
Guidelines for the management of patients
with atrial fibrillation – executive summa-
ry: a report of the American College of
Cardiology/American Heart Association
Task Force on Practice Guidelines and the
European Society of Cardiology Committee
for Practice Guidelines (Writing commit-
tee to revise the 2011 guidelines for the
management of patients with atrial fibrilla-
tion): Developed in collaboration with the
European Heart RhythmAssociation and the
Heart Rhythm Society.
Circulation
2006;
114
: 700–752.
6.
Flaker GC,
et al
. Dabigatran etexilate vs
warfarin in patients with different types of
atrial fibrillation: a subgroup analysis from
the randomised evaluation of long-term
anticoagulation therapy (RE-LY). Poster
presentation at ACC 2011.
