Endovascular Therapy for Acute Basilar Artery Occlusion
The first description of the use of IAT was published in the early 1980s. However, randomized clinical trial data for intra-arterial thrombolytic therapy for basilar artery occlusion are lacking and are limited to a single small study of only 16 patients that was prematurely terminated because of slow recruitment and withdrawal of the sale of urokinase in Australia. Patients were randomized to receive treatment with intra-arterial urokinase or control. All received heparin for a minimum of 2 days and then oral warfarin. In the eight patients who received thrombolysis, four died and the modified Rankin scale (mRS) score was 1 in the survivors. In eight patients in the control group, four died and the mRS score was 3 in the survivors. This showed no significant difference in outcome between the two groups although it did suggest a benefit for thrombolytic therapy. It is, however, certainly too small to draw meaningful conclusions and the results are not sufficient to provide randomized clinical trial evidence for or against the general application of IAT.
There have, however, been multiple series describing the use of IAT in the treatment of basilar occlusion. Unfortunately, each series differs in the method and timing of follow-up and method of documentation of favorable or poor outcome. It is therefore problematic to attempt a reliable comparison of clinical outcomes across studies and, for this reason, mortality—a relatively easily comparable outcome measure—has been used as a comparison across studies.
A large meta-analysis that incorporated 10 studies including 316 patients reported an overall recanalization rate of 64% and overall mortality of 56%. The mortality was 87% in non-recanalized patients and 37% in recanalized patients, resulting in a 48% absolute risk reduction of death (p<0.001). The rate of symptomatic intracranial hemorrhage in this analysis was only 7%.
In the most recent and the largest series to date, the data of 180 adult patients with angiographically-confirmed basilar occlusion treated with IAT at five German stroke centers were retrospectively evaluated. Patients with partial or complete recanalization had a significantly better neurological outcome than non-recanalized patients (p<0.001). For 38 (86%) of 44 patients who had no recanalization, the post-treatment outcome measured using the mRS was 5 or 6; such a poor outcome was present in only 32 (33%) of 97 patients with full recanalization and in 43% of patients with partial recanalization. Conversely, in patients with a good post-treatment outcome (mRS score 0–2), only 2% of patients had no recanalization whereas 34% had partial and 29% had complete recanalization. These results emphasize the notion that complete or at least partial recanalization of the occlusion is essential for a favorable neurological outcome. Furthermore, even partial recanalization resulted in a relatively satisfactory post-treatment mRS score of 0–4 in 57% of patients compared with 14% in non-recanalized patients. In keeping with this finding, a meta-analysis of all case series involving >10 patients with basilar occlusion who underwent IAT with urokinase and/or recombinant tissue plasminogen activator (rtPA) during the 1987–97 period (n=164 patients) found that failure to recanalize was associated with higher mortality.
Intra-arterial Thrombolysis (IAT): What is the Evidence?
The first description of the use of IAT was published in the early 1980s. However, randomized clinical trial data for intra-arterial thrombolytic therapy for basilar artery occlusion are lacking and are limited to a single small study of only 16 patients that was prematurely terminated because of slow recruitment and withdrawal of the sale of urokinase in Australia. Patients were randomized to receive treatment with intra-arterial urokinase or control. All received heparin for a minimum of 2 days and then oral warfarin. In the eight patients who received thrombolysis, four died and the modified Rankin scale (mRS) score was 1 in the survivors. In eight patients in the control group, four died and the mRS score was 3 in the survivors. This showed no significant difference in outcome between the two groups although it did suggest a benefit for thrombolytic therapy. It is, however, certainly too small to draw meaningful conclusions and the results are not sufficient to provide randomized clinical trial evidence for or against the general application of IAT.
There have, however, been multiple series describing the use of IAT in the treatment of basilar occlusion. Unfortunately, each series differs in the method and timing of follow-up and method of documentation of favorable or poor outcome. It is therefore problematic to attempt a reliable comparison of clinical outcomes across studies and, for this reason, mortality—a relatively easily comparable outcome measure—has been used as a comparison across studies.
A large meta-analysis that incorporated 10 studies including 316 patients reported an overall recanalization rate of 64% and overall mortality of 56%. The mortality was 87% in non-recanalized patients and 37% in recanalized patients, resulting in a 48% absolute risk reduction of death (p<0.001). The rate of symptomatic intracranial hemorrhage in this analysis was only 7%.
In the most recent and the largest series to date, the data of 180 adult patients with angiographically-confirmed basilar occlusion treated with IAT at five German stroke centers were retrospectively evaluated. Patients with partial or complete recanalization had a significantly better neurological outcome than non-recanalized patients (p<0.001). For 38 (86%) of 44 patients who had no recanalization, the post-treatment outcome measured using the mRS was 5 or 6; such a poor outcome was present in only 32 (33%) of 97 patients with full recanalization and in 43% of patients with partial recanalization. Conversely, in patients with a good post-treatment outcome (mRS score 0–2), only 2% of patients had no recanalization whereas 34% had partial and 29% had complete recanalization. These results emphasize the notion that complete or at least partial recanalization of the occlusion is essential for a favorable neurological outcome. Furthermore, even partial recanalization resulted in a relatively satisfactory post-treatment mRS score of 0–4 in 57% of patients compared with 14% in non-recanalized patients. In keeping with this finding, a meta-analysis of all case series involving >10 patients with basilar occlusion who underwent IAT with urokinase and/or recombinant tissue plasminogen activator (rtPA) during the 1987–97 period (n=164 patients) found that failure to recanalize was associated with higher mortality.