michael s
(Michael S)
#1
had severe pain over a few hours and has an appropriately
abnormal ECG, thrombolytic treatment should be seriously
considered. Prehospital thrombolysis has been shown to reduce
cardiac mortality compared to in-hospital thrombolysis by 17%
(p = 0.03), by reducing the mean time to treatment by about one
hour.^4 Despite this, prehospital thrombolysis has in general not
been taken up for logistical reasons.
Is one thrombolytic better than another?
Although angiographic studies show higher early patency rates
with tPA compared with SK (~70% vs ~35%), neither the GISSI-
2 study^5 nor the ISIS-3 study found any difference in 30 day
mortality rate (8.5% SK vs 8.9% tPA) and (10.6% for SK and
10.3% for tPA) respectively. In the GUSTO trial a more aggressive
regimen was used, so called front-loaded tPA, producing a small
but significant benefit favouring tPA (6.3% vs 7.3% p > 0.04).
There were, however, an excess of strokes (0.72% for tPA vs
0.54% for SK). Combining deaths and strokes there was still a
benefit favouring front-loaded tPA (6.9 % vs 7.8%).
Currently, in many countries streptokinase remains the first
line treatment for AMI. This is because the advantage for tPA is
modest and tPA is expensive ((£470) compared to SK (£80) per
patient). Since streptokinase neutralising antibodies are formed
from about day 4 onwards, tPA will need to be administered
should the patient reinfarct after this time.
The lack of any large difference in clinical outcome between
tPA and SK despite the difference in early angiographic
patency needs to be explained. TPA is locally effective, with
little systemic thrombolytic effect (for example on circulating
plasminogen). It is, however, very specific, which is the cause
for the excess in strokes. It has a short half life compared to SK.
It has been clearly shown in animal models of arterial
thrombotic occlusion that opening of the vessel by adminis-
tration of tPA may be followed by early reocclusion, perhaps
within minutes. The 90 minute angiogram cannot reflect the
consequent reocclusion of the artery, which will happen less
with SK which has a longer half life. Thus the increased
patency with tPA may not translate into a decrease in mortality.
The short half life of tPA means that heparin should be co-
administered and continued for 24 hours although true benefit
has never actually been proven.
