The MD Conference Express ISTH Special Collection - (Page 4)
nFEATUrE
New Oral Anticoagulants and
Antiplatelet Drugs
TCT 2012, Written by Toni Rizzo
ORAL ANTICOAGULANTS
Select Peer-Reviewed
Highlights on Thrombosis
and Haemostasis
From 2012
The benefit of oral anticoagulation following acute coronary syndrome (ACS) has been
demonstrated in warfarin trials, showing significant reductions in myocardial infarction (MI)
and stroke at the expense of an increased risk of bleeding. The impact of oral direct thrombin
inhibitors and direct factor Xa inhibitors in ACS patients has been the subject of several clinical
trials that were presented by Christopher B. Granger, MD, Duke University Medical Center,
Durham, North Carolina, USA.
In the Phase 3 Acute Coronary Syndrome [APPRAISE-2; Alexander JH et al. N Engl J Med 2011]
study of apixaban combined with antiplatelet therapy in high-risk ACS patients, apixaban was not
more effective than placebo (HR, 0.95; 95% CI, 0.80 to 1.11; p=0.51). The study was stopped early
because of significantly increased risk of major bleeding with apixaban (1.3%) versus placebo (0.5%;
HR, 2.59; 95% CI, 1.50 to 4.46; p=0.001).
The Efficacy and Safety Study for Rivaroxaban in Patients with Acute Coronary Syndrome
[ATLAS ACS 2-TIMI 51] trial randomized patients with recent ACS to rivaroxaban 2.5 mg BID
(n=5174), rivaroxaban 5.0 mg BID (n=5176), or placebo (n=5176) [Mega JL et al. N Engl J Med
2012]. The incidence of the primary endpoint of cardiovascular (CV) death, MI, and stroke was
8.9% with rivaroxaban (both doses) versus placebo (10.7%; HR, 0.84; 95% CI, 0.74 to 0.96; modified
intention-to-treat [mITT] p=0.008). Patients treated with low-dose rivaroxaban versus placebo had
significantly reduced rates of the primary endpoint (9.1% vs 10.7%; HR, 0.84; mITT p=0.02), CV
death (2.7% vs 4.1%; HR, 0.66; mITT p=0.002), and all-cause death (2.9% vs 4.5%; HR, 0.68; mITT
p=0.002). This survival benefit was not observed with rivaroxaban 5.0 mg. TIMI major bleeding rates
were significantly increased with rivaroxaban 2.5 mg (1.8%; HR, 3.46; p<0.001) and rivaroxaban
5.0 mg (2.4%; HR, 4.47; p<0.001) versus placebo (0.6%).
The What Is the Optimal Antiplatelet & Anticoagulant Therapy in Patients with Oral
Anticoagulation and Coronary Stenting [WOEST; NCT00769938; De Wilde W. ESC 2012] trial is the
first study to compare an oral anticoagulant regimen (warfarin and clopidogrel) with and without
aspirin in patients undergoing coronary stenting. Although the trial had some limitations, the
double- versus triple-therapy group had significantly lower TIMI bleeding (19.5% vs 44.9%; HR, 0.36;
95% CI, 0.26 to 0.50; p<0.001). Double therapy also appeared to be associated with reduced rates of
major adverse cardiac events (MACE; 11.3% vs 17.1%; HR, 0.60; 95% CI, 0.38 to 0.94; p=0.025).
The APPRAISE-2 and ATLAS-2 trials of novel factor Xa inhibitors in patients also taking aspirin
and clopidogrel both demonstrated a 3- to 4-fold increased risk of major bleeding, including
intracranial hemorrhage (ICH). Factors such as the dose, patient population, and chance may
account for the benefit observed with rivaroxaban but not with apixaban. The WOEST trial has
demonstrated the potential for a more favorable benefit/risk balance by discontinuing aspirin
in some patients on oral anticoagulants.
ANTIPLATELET AGENTS
Robert A. Harrington, MD, Stanford University Medical Center, Stanford, California, USA,
discussed the current state of adenosine diphosphate (ADP) blockers and emerging approaches to
antiplatelet therapy. Antiplatelet therapy is the cornerstone of ACS care, supported by a large body of
evidence. Studies have shown that more intense ADP blockade is better than less intense blockade.
Although most of the effect is on reduction of MI, the Efficacy and Safety of Adding Clopidogrel to
Aspirin or Use of Metoprolol in Myocardial Infarction [COMMIT; COMMIT Collaborative Group.
Lancet 2005] and PLATO trials showed that mortality reductions are possible. However, balancing
efficacy and safety is a challenge, especially with combination therapy.
4
May 2013
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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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