The MD Conference Express ISTH Special Collection - (Page 18)
CLINICAL TrIAL HIGHLIGHTS
Key safety outcomes were not significantly different with
PFT versus conventional therapy: major bleeding (2.3% vs
3.3%; HR, 0.70; 95% CI, 0.43 to 1.14; p=0.15), minor bleeding
(1.0% vs 1.7%; HR, 0.57; 95% CI, 0.28 to 1.16; p=0.12), and
major or minor bleeding (3.1% vs 4.5%; HR, 0.69; 95% CI,
0.46 to 1.05; p=0.08).
The ARCTIC study results show that PFT with
antiplatelet adjustment before and after stenting does not
improve clinical outcomes versus conventional treatment
without PFT. These results do not support the routine use of
PFT in patients undergoing stenting. The ARCTIC-2 study,
in which a second randomization was performed at 1 year
after the initial randomization to determine the effect of
continuation versus interruption of clopidogrel is ongoing.
The Tailored Antiplatelet Therapy Versus Recommended
Dose of Prasugrel [ANTARCTIC; NCT01538446] study will
evaluate the value of PFT in elderly patients, with a focus on
bleeding events. Whether PFT-guided antiplatelet therapy
provides benefit for specific types of ischemic events
such as spontaneous MI or stent thrombosis is unclear,
as the ARCTIC trial was not powered for these individual
endpoints and primary findings were largely driven by
periprocedural events.
Long-Term Dabigatran Extension
Study for Stroke Prevention in
Treatment for Atrial Fibrillation
arm and 3397 (75%) in the 150-mg arm were beeing
followed at a site participating in RELY-ABLE.
A total of 2914 patients receiving dabigatran 110 mg
and 2937 patients receiving dabigatran 150 mg were
enrolled in RELY-ABLE, and 2511 and 2508 patients,
respectively, completed the study, representing 86%
and 85% of the patients.
During 2.3 years of additional dabigatran treatment after
RE-LY (total mean follow up of 4.3 years), rates of stroke and
major bleeding remained low and comparisons of the two
doses were consistent with those observed during the main
RE-LY trial. The rates of stroke and myocardial infarction (MI)
from the RELY-ABLE and RELY trials are compared in Table 1.
At a mean follow-up of 2.3 years, the cumulative risk of
stroke or systemic embolism was 1.46%/year with dabigatran
150 mg versus 1.60%/year with dabigatran 110 mg
(HR, 0.91; 95% CI, 0.69 to 1.20). Other endpoint results
at 2.3 years were stroke, 1.24%/year with dabigatran
150 mg versus 1.38%/year with dabigatran 110 mg (HR, 0.89;
95% CI, 0.66 to 1.21); ischemic stroke, 1.15%/year versus
1.24%/year (HR, 0.92; 95% CI, 0.67 to 1.27); hemorrhagic
stroke, 0.13%/year versus 0.14%/year (HR, 0.89; 95% CI, 0.34
to 2.30); MI, 0.69%/year versus 0.72%/year (HR, 0.96; 95%
CI, 0.63 to 1.45); and pulmonary embolism, 0.13%/year
versus 0.11%/year (HR, 1.14; 95% CI, 0.41 to 3.15).
Table 1. RELY-ABLE and RE-LY Efficacy Outcomes for
Dabigatran 110 and 150 mg.
Endpoint
RELY-ABLE
110 mg
(%/Year)
RELY-ABLE
150 mg
(%/Year)
RE-LY
110 mg
(%/Year)
RE-LYLY
150 mg
(%/Year)
Stroke or
systemic
embolism
1.60
1.46
1.53
1.11
AHA 2012, Written by Toni Rizzo
Previously, the Randomized Evaluation of Long-Term
Anticoagulation Therapy [RE-LY] trial evaluated two doses
of dabigatran (110 and 150 mg BID; open dabigatran but
blinded dose) versus warfarin (open-label) in patients with
nonvalvular atrial fibrillation and at least 1 risk factor for
stroke [Flaker et al. J Am Coll Cardiol 2012]. The goal of the
RELY-ABLE extension study [NCT00808067] presented by
Stuart J. Connolly, MD, McMaster University, Hamilton,
Ontario, Canada, was to describe the long-term efficacy and
safety of ongoing dabigatran therapy after the RE-LY trial.
Patients who had been randomized to dabigatran
and were still taking it at then end of the the blinded
dose of dabigatran taken in RE-LY trial were eligible for
the was continued in the RELY-ABLE extension study.
Patients continued on the same dose of dabigatran (the
dose of dabigatran remained blinded) trial for a mean of
2.3 years. In the RE-LY trial, patients were randomized
to dabigatran 110 mg (n=6015) or dabigatran 150 mg
(n=6076) in a blinded fashion, or open-label warfarin
(n=6022). Among these, 4492 (75%) in the 110-mg arm and
4519 (75%) in the 150-mg arm completed RE-LY and were
still receiving dabigatran. Of these, 3395 (76%) in the 110-mg
18
May 2013
SAll stroke
1.38
1.24
1.44
1.01
Ischemic stroke
1.24
1.15
1.34
0.92
Hemorrhagic
stroke
0.14
0.13
0.12
0.10
Myocardial
infarction
0.72
0.69
0.72
0.74
Pulmonary
embolism
0.11
0.13
0.12
0.15
Adapted from Connolly SJ et al. Dabigatran Versus Warfarin in Patients with Atrial Fibrillation.
N Engl J Med 2009;361:1139-51.
Stroke and systemic embolism results for patients in
the RELY-ABLE study who received 150 mg versus 110 mg
dabigatran at a mean follow-up of 4.25 years were 0.89%/
year versus 1.05%/year at a mean follow-up of 4.25 years,
and 1.25%/year versus 1.54%/year in all dabigatran patients
(RE-LY and RELY-ABLE) at a mean follow-up of 3 years
(1.25%/year vs 1.54%/year).
Patients treated with dabigatran 150 mg had higher
rates of major bleeding (3.74%/year) compared with
dabigatran 110 mg (2.99%/year) at 2.3 years in the RELYwww.mdconferencexpress.com
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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
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