The MD Conference Express ISTH Special Collection - (Page 10)
CLINICAL TrIAL HIGHLIGHTS
Moderate PE Treated with
Thrombolysis (MOPETT Study)
ACC 2012, Written by Maria Vinall
Pulmonary embolism (PE) is one of the most common
preventable causes of death (responsible for >100,000
deaths annually) and the third leading cause of
cardiovascular mortality. Thrombolysis with standard
doses of 100 mg tissue plasminogen activator (t-PA) over
2 hours is recommended in appropriately selected severe
PE patients (patients with hemodynamic instability
and shock), but these patients only represent 5% of
all presentations with PE. Patients with moderate PE
constitute a more prevalent population; however, there
are often concerns about major bleeding (which occurs in
6% to 20% of cases) and intracranial hemorrhage (ICH; 2%
to 6% of cases) in moderate PE patients when larger doses of
t-PA are employed. In addition, practitioners are hesitant
to use t-PA when patients are hemodynamically stable
and/or receiving concomitant parenteral anticoagulation
due to concern that the risks outweigh the benefits. PE is
exquisitely sensitive to thrombolysis, as the lungs are the
point of convergence of venous circulation; so, a majority
of IV-delivered t-PA converges to the clot, making t-PA ideal
for the treatment of this population of patients.
New data from the Moderate Pulmonary Embolism
Treated with Thrombolysis [MOPETT] study, presented by
Mohsen Sharifi, MD, A.T. Still University, Mesa, Arizona,
USA, suggest that moderate PE patients may be managed
with reduced-dose t-PA and modified anticoagulation.
MOPETT was a randomized trial of 121 patients (45%
men; mean age 59 years). Sixty-one patients received
t-PA that was dose-adjusted for weight (for those ≥50 kg,
an initial dose of 10 mg t-PA over 1 minute, followed by a
40-mg infusion over 2 hours; for those <50 kg, a total t-PA
dose of 0.5 mg/kg, delivered as an initial dose of 10 mg
over 1 minute, followed by the remainder as an infusion
over 2 hours) in addition to a 20% to 30% reduction in
anticoagulant dose (either enoxaparin or heparin), and
60 subjects received anticoagulation alone (standard
of care). The coprimary endpoints were pulmonary
hypertension (PH) and a composite of PH plus recurrent PE
after 28 months of follow-up. The determination of PH was
by echocardiography, defined as an estimated pulmonary
artery systolic pressure (PASP) >40 mm Hg. Secondary
endpoints included in-hospital bleeding, duration of
hospitalization, and mortality. Patients were included in this
study if they had symptomatic PE plus two of the following
risk factors for post-PE mortality: chest pain, tachypnea
>22 respirations per minute, tachycardia resting heart
rate >90 bpm, dyspnea, jugular venous pressure >12 cm
H20, cough, or oxygen desaturation <90%.
10
May 2013
Serial changes in PASP from baseline to 28 months by
treatment strategy are shown in Table 1. After 28 months,
16% of t-PA patients experienced PH (the first coprimary
endpoint) compared with 57% of those who were assigned
standard anticoagulation (p<0.001). Patients who were
treated with t-PA also had significantly fewer incidences of
the second coprimary endpoint, a composite of PH plus
recurrent PE at 28 months (16% vs 63%; p<0.001). Secondary
events occurred infrequently, in particular mortality, and
are shown according to treatment assignment in Table 2. No
significant in-hospital bleeding occurred with either strategy.
Table 1. Serial Changes in PASP from Baseline to 28 Months
by Treatment Strategy.
t-PA (n=58)
Standard of Care p Value
(n=56)
Initial PASP (mm Hg)
50±6
51±7
0.40
PASP (mm Hg) change
within 48 hours
-16±3
-5±2
<0.001
PASP at 6 months
31±6
49±8
<0.001
PASP at 28 months
28±5
43±6
<0.001
PAH at 28 months*
9
32
<0.001
PAH and recurrent PE at
28 months*
9
35
<0.001
*PAH=pulmonary arterial hypertension; PASP=pulmonary artery systolic
>40 mm Hg; PE=pulmonary embolism; t-PA=tissue plasminogen activator.
pressure
Table 2. Secondary Events by Treatment Strategy.
t-PA
(n=61)
Standard of
Care (n=60)
p Value
Recurrent PE (%)
0
3 (5)
0.077
Mortality (%)
1 (1.6)
3 (5)
0.301
Recurrent PE + mortality (%)
1 (1.6)
6 (10)
Hospital stay, days
2.2±0.5
4.9±0.8
0.0489
<0.001
PE=pulmonary embolism; t-PA=tissue plasminogen activator.
The authors concluded that the use of low-dose
thrombolysis appeared to be safe and effective in moderate
PE to reduce PH, recurrent PE, and hospital stay without
an increase in bleeding risk or ICH. However, hard clinical
events, such as mortality, clinically evident right-heart
failure, and major bleeding events, were infrequent. Larger
and long-term studies that test this strategy in representative
patients are necessary to ultimately determine whether
modified aggressive reperfusion therapy provides more
benefit than harm in PE.
Results of the WOEST Trial
ESC 2012, Written by Maria Vinall
Results of the first randomized trial to address optimal
antiplatelet therapy in patients on oral anticoagulants
(OACs) undergoing coronary stenting showed that
treatment with dual antithrombotic therapy (OAC +
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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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