The MD Conference Express ISTH Special Collection - (Page 7)
Figure 1. All-Cause Mortality.
Aspirin=77 (1.4%/pt-yr)
Aspirin+Clopidogrel=133 (2.1%/pt-yr)
0.4
Probability of Death
0.5
HR 1.5 (1.1 to 2.0)
p=0.005
0.3
Group 1: Aspirin+Clopidogrel
0.2
0.1
Group 2: Aspirin+Placebo
0
Group 1:
Group 2:
0
1
2
3
1517
1503
1312
1339
1087
1087
4
5
Time (Years)
647
863
623
648
390
420
6
7
8
211
237
98
106
3
5
Reproduced with permission from OR Benavente, MD, FRCP(C).
Table 1. Major Hemorrhages.
Aspirin
Aspirin+
Clopidogrel
HR
(95% CI)
p Value
n
%/pt-yr
n
%/pt-yr
All hemorrhages
56
1.10
105
2.10
2.0
(1.40-2.70)
<0.001
CNS
hemorrhages
15
0.28
22
0.42
1.5
(0.79-2.90)
0.21
Intercerebral*
7
0.13
13
0.25
1.9
(0.75-4.70)
0.18
Subdural†
6
0.11
6
0.11
1.0
(0.33-3.20)
0.95
Other ‡
3
0.005
2
0.038
0.7
(0.12-4.20)
0.70
42
0.79
87
1.70
2.2
(1.50-3.10)
<0.001
Non-CNS
hemorrhages
*Intraparenchymal, spinal; †Subdural, epidural; ‡Subarachnoid, other.
Apixaban Superior to Warfarin in
Patients with Atrial Fibrillation as
Well as Prior Stroke or TIA
ARISTOTLE was a randomized, double-blind, doubledummy trial that included subjects who were aged ≥75
years and had AF and at least one additional risk factor for
stroke (previous stroke, TIA, or systemic embolism [SE];
symptomatic heart failure within the previous 3 months or
left ventricular ejection fraction ≤40%; diabetes mellitus; or
hypertension requiring pharmacologic treatment). A total
of 18,201 patients were randomized to apixaban 5 mg oral
BID or warfarin (target INR 2 to 3). The primary outcome
was ischemic or hemorrhagic stroke or SE. The trial was
designed to test for noninferiority, with key secondary
objectives of testing for superiority with respect to the
primary outcome and to the rates of major bleeding and
death from any cause.
The primary objective of the stroke substudy was to
determine whether apixaban, as compared with warfarin,
had the same advantages in patients with prior stroke
or TIA (n=3436) as in all patients (n=14,765) with AF in
the ARISTOTLE trial. The primary efficacy outcome was
ischemic or hemorrhagic stroke or SE. The primary safety
outcome was major bleeding according to the International
Society of Thrombosis and Haemostasis (ISTH) definition.
The demographic and clinical characteristics of the Prior
Stroke/TIA patients compared with the No Prior Stroke/TIA
patients were essentially the same, with 19.5% of the 18,201
ARISTOTLE patients having had a prior stroke or TIA. The
only important difference was in the CHADS2 score (mean,
SD): 3.7 (0.9) for the Prior Stroke/TIA group versus 1.7 (0.8)
for the No Prior Stroke/TIA group. Only 15% of the No Prior
Stroke/TIA group had a CHADS2 score that high.
The primary outcome data (Figure 1) showed a
considerably higher event rate in the warfarin/Prior Stroke
group compared with the apixaban/Prior Stroke group,
indicating a greater absolute benefit in the apixaban group.
Figure 1. Stroke Substudy Primary Outcome.
10
8
The recent Apixaban Compared with Warfarin in Patients
with Atrial Fibrillation and Prior Stroke or Transient
Ischemic Attack trial [Granger CB et al. N Engl J Med 2011;
ARISTOTLE; NCT00412984] found apixaban to be superior
to warfarin for stroke prevention in a wide range of atrial
fibrillation (AF) patients, with significantly lower bleeding
risk and lower risk of all-cause mortality [Littrell R, Flaker
G. Expert Rev Cardiovasc Ther 2012]. J. Donald Easton,
MD, FAHA, University of California, San Francisco,
San Francisco, California, USA, presented results of a
comparison of apixaban with warfarin in patients with AF
and prior stroke or transient ischemic attack (TIA).
Percent with Event
ISC 2012, Written by Rita Buckley
Warfarin/Prior Stroke
6
Apixaban/Prior Stroke
4
Warfarin/No Prior Stroke
2
Apixaban/No Prior Stroke
0
Treatment
Apixaban
Warfarin
Apixaban
Warfarin
Prior
Stroke
Yes
Yes
No
No
0
6
12
1694
1742
7426
7339
1604
1643
7122
6977
1547
1564
6893
6737
Months
18
1066
1092
4985
4880
24
30
560
554
2904
2851
263
263
1491
1505
Reproduced with permission from JD Easton, MD.
Select Peer-Reviewed Highlights on Thrombosis and Haemostasis From 2012
7
Table of Contents for the Digital Edition of The MD Conference Express ISTH Special Collection
The MD Conference Express ISTH Special Collection
Table of Contents
New Oral Anticoagulants and Antiplatelet Drugs
SPS3 Study Does Not Support the Use of Combination Therapy for Stroke Prevention
Apixaban Superior to Warfarin in Patients with Atrial Fibrillation as Well as Prior Stroke or TIA
The HOST-ASSURE Randomized Trial
Oral Rivaroxaban Alone for Symptomatic Pulmonary Embolism
Moderate PE Treated with Thrombolysis (MOPETT Study)
Results of the WOEST Trial
Genetic Determinants of Variability in Dabigatran Exposure
Rivaroxaban of Benefit in STEMI: ATLAS ACS 2-TIMI 51
Hyporesponsiveness to Clopidogrel Does Not Predict 1-Year Mortality
First Large-Scale Platelet Function Evaluation in an Acute Coronary Syndrome Trial: The Trilogy ACS-Platelet Function Substudy
ASPIRE: Using Aspirin to Prevent Recurrence of VTE
ARCTIC: Randomized Trial of Bedside Platelet Function Monitoring
Long-Term Dabigatran Extension Study for Stroke Prevention in Treatment for Atrial Fibrillation
Clopidogrel Plus Aspirin Reduces Risk of Recurrent Stroke: The CHANCE Trial
Anticoagulation and Antithrombotic Therapy in Atrial Fibrillation
Balancing Bleeding and Ischemic Risk in the Acute and Long-Term Setting
Safety and Efficacy of Anticoagulants
The MD Conference Express ISTH Special Collection
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