Reduced dosage of tenecteplase in elderly patients undergoing a pharmaco-invasive strategy.
Delays in achieving timely reperfusion in patients with acute coronary syndrome with ST elevation (STEACS), whether through fibrinolysis or primary percutaneous coronary intervention (PCI), are associated with increased mortality. European guidelines establish a target reperfusion time of 120 minutes after the first medical contact (FMC). However, many sites lack an interventional cardiology lab, thus requiring a speedy transfer to another facility or the use of fibrinolytics to achieve early reperfusion.
In the STREAM-1 study, in patients with symptom onset within 3 hours who are not eligible for PCI within 60 minutes, a pharmaco-invasive strategy was found to produce similar rates of death, shock, heart failure, or new acute myocardial infarction (AMI) compared with primary PCI after one hour. However, there was an increase in intracranial hemorrhage in patients over 75 years old. As a result, the protocol was amended to reduce the dose of tenecteplase according to weight, resulting in no additional cases of intracranial bleeding in the 97 patients treated after such a modification.
The objective of the study conducted by Van de Werf et al. was to investigate whether a reduced dose of tenecteplase was a safe alternative in elderly patients with STEACS who experienced early symptoms and were unable to undergo early primary PCI. This prospective, randomized, open-label, and multicenter study was conducted in 49 centers across 10 countries. Enrollment included patients over 60 years old (initially 70 years old but modified due to slow recruitment) who weighted at least 55 kg. Patients had to undergo FMC within 3 hours of symptom onset, ST elevation on ECG, and not be candidates for primary PCI within 1 hour after FMC.
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Patients were randomly assigned 2:1 to receive a pharmaco-invasive strategy or undergo primary PCI. Patients in the pharmaco-invasive strategy received a reduced and adjusted dose of tenecteplase (bolus), 150 to 325 mg of aspirin, 300 mg of clopidogrel, and 0.75 mg/kg of subcutaneous enoxaparin, in addition to an additional intravenous dose of 30 mg in patients who were 75 years old or younger (after the amendment). After achieving successful reperfusion criteria, coronary angiography was conducted within 6 to 24 hours after randomization.
The main efficacy outcomes were successful reperfusion (percentage of patients with resolution of ST segment ≥50%) and a composite clinical outcome of all-cause mortality, shock, heart failure, and new AMI at 30 days. Researchers analyzed TIMI flow in coronary angiography, and adverse events such as stroke and non-intracranial bleeding were evaluated to assess strategy safety.
A total of 604 patients were included, with 401 assigned to the pharmaco-invasive strategy and 203 to primary PCI. The average age was 70.5 years, and 27.5% of patients were 75 years old or older. Nearly a third of the patients were female. The average time from symptom onset to randomization was 97 minutes in the pharmaco-invasive group and 92 minutes in the PCI group. The average time to tenecteplase bolus was 10 minutes, and the time to arterial introducer insertion was 81 minutes.
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An analysis of the ECG at 90 minutes after the intervention showed ST segment resolution ≥50% in 70.3% of patients receiving the pharmaco-invasive treatment, resulting in an average reduction of ST elevation from 3.0 to 1.0 mm. ST segment resolution ≥50% was observed in 85.2% of patients in the tenecteplase group compared with 78.4% in the PCI group. TIMI-3 flow after tenecteplase was 53.8%, compared with 18.9% before primary PCI (after intervention: 87% TIMI-3).
The primary efficacy endpoint at 30 days was similar with both strategies: 12.8% in the pharmaco-invasive group and 13.3% in the primary PCI group (relative risk [RR]: 0.96; 95% confidence interval [CI]: 0.62-1.48). Mortality from all causes and from cardiac causes were 9.3% and 7.3% in the pharmaco-invasive group, and 8.9% and 8.4% in the primary PCI group, respectively. There were no significant differences in any of the individual clinical outcomes.
Regarding safety, there were 10 cases of stroke and 6 cases of intracranial bleeding in the tenecteplase group (1.5%), and 50% of these cases were attributed to poor anticoagulation or blood pressure control, resulting in high mortality.
Conclusions
In conclusion, the use of a reduced dose of tenecteplase in elderly patients (with an average age of 70 years) showed adequate effectiveness. However, due to the association of isolated cases of intracranial hemorrhage with high mortality, patient selection should be careful and specific, considering delays in the possibility of performing primary PCI.
Dr. Omar Tupayachi.
Member of the Editorial Board of SOLACI.org.
Reference: Van de Werf F, Ristić AD, Averkov OV, et al. Half-Dose Tenecteplase or Primary Percutaneous Coronary Intervention in Older Patients With ST-Segment-Elevation Myocardial Infarction in STREAM-2: A Randomized, Open-Label Trial [published online ahead of print, 2023 Jul 13]. Circulation. 2023;10.1161/CIRCULATIONAHA.123.064521. doi:10.1161/CIRCULATIONAHA.123.064521.
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