Potential cost effectiveness of tissue plasminogen activator among patients previously treated with streptokinase

A major limitation of streptokinase is the development and persistence of problematic neutralizing antibodies that have the potential to limit the effectiveness of repeat streptokinase therapy. Accordingly, tissue-type plasminogen activator (t-PA) is frequently administered to patients with recurrent infarction presenting more than four days from previous treatment with streptokinase.

To explore the marginal cost effectiveness of the use of t-PA among patients with resistance to streptokinase.

A model was developed incorporating short term (five- to six-week) costs and mortality data for various thrombolytic strategies. It was assumed that streptokinase would be clinically ineffective when administered to streptokinase-resistant patients. Sensitivity analyses were performed varying the baseline mortality, the proportion of patients resistant to streptokinase and the absolute survival benefit of t-PA compared with streptokinase.

In the absence of streptokinase resistance, streptokinase is a cost effective strategy for patients with suspected myocardial infarction, even when the expected mortality is low. In the presence of streptokinase resistance, the combination of streptokinase and acetylsalicylic acid is most cost effective when rates of resistance are low ($16,389 per short run survivor with 5% resistance versus $21,306 with 50% resistance). t-PA is a cost effective alternative when rates of resistance are high ($54,158 per short run survivor with 50% resistance) assuming a 1% absolute risk reduction in mortality. As the level of resistance decreases, however, t-PA becomes a less cost effective choice ($203,092 per short run survivor with 5% resistance). However, t-PA is always more cost effective in the presence of any streptokinase resistance than when it is administered for an index myocardial infarction.

This analysis shows that using t-PA in patients previously treated with streptokinase is a cost effective strategy. t-PA becomes less cost effective as the percentage of patients with streptokinase resistance decreases, particularly when the absolute risk reduction favouring t-PA over streptokinase is small. Nevertheless, if the early mortality advantage is sustained, very favourable cost effectiveness ratios are attained with t-PA even when the risk of resistance is low. t-PA used in the presence of streptokinase resistance is always more cost effective than when it is used for a first myocardial infarction.