Why not trial intra-arterial lytics in basilar artery thrombosis

Article by Powers WJ. Intrarterial thrombolysis for basilar artery thrombosis. Trial it. Stroke. 2007; 38: 704-706. This article stresses the lack of current evidence in favor of arterial lytics therapy for ba thrombosis and the need for clinical trials. Macleod et al.(2005; 20: 12-17)Cerebrovascular Disease) is only randomized trial and it was prematurely terminated due to shortage of urokinase. Authors comment: "However, not every treatment requires a randomized clinical
trial to establish efficacy. Observational studies may provide
compelling evidence of treatment efficacy if treatment effects
are sufficiently large and consistent.6 Thus, the following 2
conditions must be met: (1) outcomes in untreated patients
are consistent; and (2) outcomes in treated patients are
consistently superior by a large margin. "". Lindsberg and Mattle have recently reviewed data on
344 patients from 11 different publications who were treated
with intra-arterial thrombolytic therapy for acute basilar
artery occlusion.5 Good outcome was achieved in 17% to
40% cases with a mean value of 24%. Those treated within
6 hours did not have a better outcome than those treated
after 6 hours.18,19 These values are not superior to the 30% to
67% good outcomes in patients who did not receive intraarterial
therapy reported in 4 recent hospital-based series
cited above. However, such comparisons across observational
studies are problematic because of differences in eligibility
criteria and in definitions of favorable outcome among the
different studies. In 1988, Hacke et al published an observational
study in which they compared 43 patients who receive
intra-arterial thrombolytic therapy for vertebral basilar thrombosis
to 22 historical controls from their center using the same outcome definition. significant benefit of intra-arterial thrombolysis in producing
favorable outcome (P[1]0. 017) and survival (P[1]0.0005).11
However, this conclusion was based on a flawed comparison
of 22 controls to only those 19 patients in whom successful
recanalization was achieved, not to the total group of 43 who
underwent thrombolytic therapy. This analytic approach is
not valid. Spontaneous recanalization of basilar artery occlusion
occurs in a substantial number of patients.20 Patients with
high levels of plasminogen activator inhibitors have both
reduced recanalization to exogenous thrombolytic agents and
reduced endogenous thrombolysis.21,22 Thus, selecting only
those patients with successful recanalization to exogenous
thrombolytic agents will also select those with the best
chance for spontaneous endogenous thrombolysis. Comparing
this selective subgroup to the full spectrum of control
patients will yield an invalid, overestimation of the treatment
effect. The more appropriate analysis based on the intentionto-
treat principle reveals that favorable outcome was
achieved in 10 of 43 treated patients and 3 of 22 untreated
patients (P[1]0.22). This study actually failed to demonstrate,
even with the use of historical controls, any significant benefit for intra-arterial thrombolytic therapy in this condition. "
Unfortunately, this therapy is not without either risk
or expense. The risk of symptomatic hemorrhage is 8% and
these may be fatal.5,23 Costs for thrombolytic drugs ($1000 to
$3000), cerebral arteriography ($4000 to $8000) and an intensive
care unit bed ($2300 to $3000/day) add substantial burdens
to a healthcare system that is already strained with no room to
grow.24,25,26 These procedural risks and expenses can be justified
only if the treatment is sufficiently effective to provide an
improvement in clinical outcome to outweigh the procedural
risks and a reduction in long-term costs to outweigh the
procedural expenses. In the absence of evidence for efficacy, the
procedural risks and expenses remain with nothing to outweigh
them.