Recent evidence suggests that half-dose thrombolysis
for pulmonary embolism may provide similar efficacy with reduced bleeding
risk compared with full-dose
therapy, but comparative studies are lacking. We aimed to evaluate the effectiveness and safety of half-dose
alteplase for treatment of pulmonary embolism.
A retrospective cohort study comparing outcomes in patients receiving half-dose
(50 mg) versus full-dose
(100 mg) alteplase for pulmonary embolism. We used propensity score matching and sensitivity analyses to address confounding and hospital-level clustering.
Data from 420 hospitals obtained from the Premier Healthcare Database between January 2010 and December 2014.
Adult critically ill patients with acute pulmonary embolism treated with IV alteplase therapy.
Measurements and Main Results:
This study included 3,768 patients: 699 (18.6%) in the half-dose
and 3,069 (81.4%) in the full-dose
group. At baseline, patients receiving half-dose
alteplase required vasopressor therapy (23.3% vs 39.4%; p
< 0.01) and invasive ventilation (14.3% vs 28.5%; p
< 0.01) less often, compared with full dose
. After propensity matching (n
= 548 per group), half-dose
alteplase was associated with increased treatment escalation (53.8% vs 41.4%; p
< 0.01), driven mostly by secondary thrombolysis
(25.9% vs 7.3%; p
< 0.01) and catheter thrombus fragmentation (14.2% vs 3.8%; p
< 0.01). Hospital mortality was similar (13% vs 15%; p
= 0.3). There was no difference in cerebral hemorrhage (0.5% vs 0.4%; p
= 0.67), gastrointestinal bleeding
(1.6% vs 1.6%; p
= 0.99), acute blood loss anemia (6.9% vs 4.6%; p
= 0.11), use of blood products (p
> 0.05 for all), or documented fibrinolytic adverse events (2.6% vs 2.8%; p
Compared with full-dose
was associated with similar mortality and rates of major bleeding
. Treatment escalation occurred more often in half-dose
–treated patients. These results question whether half-dose
alteplase provides similar efficacy with improved safety, and highlights the need for further study before use of half-dose
alteplase therapy can be routinely recommended in patients with pulmonary embolism.