Half-dose tenecteplase safe and effective for STEMI without timely PCI

Pharmaco-invasive therapy with half-dose tenecteplase may provide a safe and effective reperfusion alternative in elderly patients with ST-segment elevation myocardial infarction (STEMI) who could not undergo primary PCI within 1 hour. The rate of intracranial haemorrhage (ICH) in the tenecteplase group was higher than anticipated.

A significant amount of patients with STEMI do not receive primary PCI within 120 minutes after the first medical contact, which elevates their risk of death. In these cases, a pharmaco-invasive strategy is recommended. However, full-dose anteplase or tenecteplase are associated with increased rates of ICH and major non-intracranial bleeding from the age of about 60 years onwards, as was shown by the ASSENT-4 PCI (NCT00168792) and the STREAM-1 (NCT00623623) trials [1,2].

The STREAM-2 trial (NCT02777580) was an investigator-initiated, prospective, randomised open-label trial conducted in 49 centres in 10 countries. The trial set out to compare the safety and efficacy of reperfusion with half-dose tenecteplase with primary PCI among STEMI patients ≥60 years who could not have primary PCI within 1 hour. The 604 participants had a STEMI <3 hours from symptom onset with ≥2 mm ST segment elevation in ≥2 contiguous leads.

The participants were randomised 2:1 to half-dose tenecteplase followed by PCI within 6–24 hours (n=401) or primary PCI (n=203). The mean patient age was 71 years; 32% were women. The duration of follow-up was 30 days. The mean systolic blood pressure was 134 mmHg, and the mean heart rate was 76 bpm. There was a difference of 80 minutes in the time to treatment; the time delay was 110 minutes in the half-dose tenecteplase group versus 190 minutes in the primary PCI group (P<0.001).

The primary clinical efficacy outcome was a composite of death, heart failure, recurrent MI (reMI), and/or shock at 30 days. The clinical efficacy outcomes are shown in the Table.

Table: The primary clinical efficacy outcomes of STREAM-2. Derived from [3]



CI, confidence interval; reMI, recurrent myocardial infarction; HF, heart failure; TNK, tenecteplase; PCI, percutaneous coronary intervention.

The clinical safety at 30 days in the half-dose tenecteplase compared as follows to the direct PCI group:

• total stroke: 2.3% versus 0.5% (RR 4.57; 95% CI 0.58–35.80; P>0.05);
• ICH: 1.5% versus 0% (RR 6.61; 95 CI 0.81–53.89; P=ns); and
• major non-ICH: 1.3% versus 1.0% (RR 1.27; 95% CI 0.25–6.48; P>0.05).

In the half-dose tenecteplase group, 3 of the 6 cases of ICH were attributed to protocol violations; non-intracranial bleeding was low overall.

1. Van der Werf F, et al. Lancet. 2006;367(9510):569–78.
2. Armstrong PW, et al. N Engl J Med 2013;368:1379–87.
3. Van de Werf F, et al. Pharmaco-invasive Reperfusion Strategy With Half-dose Tenecteplase In Older St-elevation Myocardial Infarction Patients. Session 407-12, ACC Scientific Session 2023, 4–6 March, New Orleans, USA.

 

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Posted on 7 June, 2023