reteplase
Last reviewed 01/2018
Reteplase is a recombinant for of tissue plasminogen activator that lacks the finger, epidermal growth factor and kringle-1 domains. The result of these deletions is:
- prolonged plasma half life
- reduced fibrin specificity
Reteplase is indicated up to 12 hours after symptom onset. It is given as two IV bolus injections 30 minutes apart. It is estimated that reteplase represents between 12% and 15% of thrombolytic drug use in the UK.
Reteplase has also been compared with streptokinase in a study involving 5986 patients (the INJECT study). This study found an absolute difference of 0.5% (95% CI - 1.98% to 0.96%) in 35-day mortality in favour of reteplase (not statistically significant). If it is accepted that a 1% difference in mortality is the limit of equivalence in thrombolytic therapy, this suggests that it is unlikely that reteplase is inferior to streptokinase. An alternative interpretation is that in terms of overall effects on mortality and disabling stroke reteplase may be inferior to streptokinase, as the trial also found a statistically significantly lower risk of haemorrhagic stroke (odds ratio 2.1; 95% CI 1.02 to 4.31) in the streptokinase group. However, the trial also found that the rates of heart failure (23.6% vs 26.3%, p< 0.05) and allergic reactions (1.1% vs 1.8%, p< 0.05) were statistically significantly lower in the reteplase group.
Reteplase has also been compared with accelerated alteplase in one relatively small (n = 324) study that examined intermediate angiographic endpoints of coronary vessel patency (RAPID-2), and one larger study that examined patient-focused endpoints (GUSTO-III, n = 15,059). GUSTO-III was designed to test the clinical superiority of reteplase over accelerated alteplase, following the findings in RAPID-2 of better coronary artery patency with reteplase. However, GUSTO-III found no statistically significant difference between the two drugs, in terms of survival or adverse effects. The mortality rate at 30 days was 7.5% in the reteplase group and 7.2% in the accelerated alteplase group: an absolute risk reduction of 0.23% in favour of accelerated alteplase (95% CI Ð1.10% to 0.66%). Given the confidence limits, reteplase cannot be considered as equivalent to accelerated alteplase.
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