The Assessment of the Safety and Efficacy of a New Treatment Strategy with percutaneous coronary intervention (ASSENT-4 PCI) study was intended to be a large randomised trial in patients facing delays to intervention in the range of 1 to 3 hours. PCI is more effective than thrombolytic therapy in patients with ST-elevation acute myocardial infarction (STEMI) when the time to treatment is short. The aim of ASSENT-4 PCI was to investigate whether full-dose tenecteplase administered prior to a delayed percutaneous coronary intervention (facilitated PCI) could mitigate the negative effect of the delay to PCI.
The study was stopped prematurely on the recommendation of the Data and Safety Monitoring Board due to higher mortality in the facilitated PCI group compared to the standard PCI group.
The ASSENT-4 PCI study randomly assigned 1,667 (of a planned 4,000) patients with ST-elevation myocardial infarction (STEMI) of ≤6 h duration (scheduled to undergo PCI with an anticipated delay of 1 to 3 h) to standard PCI (n=838) or PCI preceded by full-dose tenecteplase (n=829). All patients received aspirin and a bolus, without an infusion, of unfractionated heparin. Patients were enrolled from 24 countries at tertiary care hospitals, community hospitals without PCI centres, and ambulances in which pre-hospital thrombolysis was available.
The primary endpoint was a composite of 90-day mortality or cardiogenic shock* or congestive heart failure*.
*adjudicated by the Clinical Event Committee
ASSENT-4 PCI: STUDY DESIGN
The ASSENT trials: ASSENT-2, ASSENT-3/ ASSENT 3-PLUS, ASSENT-4 PCI have provided a deep insight into the effects of tenecteplase. The table below gives a brief summary of these studies.
The time between onset of symptoms and randomisation and catheterisation was similar between groups. The median time to administration of tenecteplase was 10 min. The time delay to PCI was 107 min in the PCI only group and 115 min in the facilitated PCI group.
The primary endpoint was significantly higher in the facilitated PCI group than in the standard PCI group (19% versus 13%; relative risk 1.39; 95% confidence interval [CI] 1.11 to 1.74; p=0.0045). However, there was no significant difference in any of the individual components of this composite endpoint (death, CHF, cardiogenic shock).
The facilitated PCI group had higher rates of stroke (1.8% versus 0%; p<0.0001), re-infarction (6% versus 4%; p=0.0279), repeat target revascularisation (7% versus 3%; p=0.0041) than the standard PCI group within 90 days. However, there was no significant difference in the rate of major non-cerebral bleeding complications (6% versus 4%; p=0.3118).
ASSENT-4 PCI: Kaplan-Meier curve for primary endpoint
Facilitated PCI, using full-dose tenecteplase 1-3 hours prior to PCI was associated with more major adverse events than PCI alone in STEMI and cannot be recommended.
- ASSENT-2 Investigators. Single-bolus tenecteplase compared with front-loaded alteplase in acute myocardial infarction: the ASSENT-2 double-blind randomised trial. Lancet 1999;354:716-722.
- Sinnaeve P, et al. One-year follow-up of the ASSENT-2 trial: a double-blind, randomized comparison of a single-bolus tenecteplase and front-loaded alteplase in 16,949 patients with ST-elevation acute myocardial infarction. Am Heart J 2003;146:27-32.
- ASSENT-3 Investigators. Efficacy and safety of tenecteplase in combination with enoxaparin, abciximab, or unfractionated heparin: the ASSENT-3 randomised trial in acute myocardial infarction. Lancet 2001;358:605-613.
- Wallentin L, et al. Efficacy and safety of tenecteplase in combination with the low-molecular-weight heparin enoxaparin or unfractionated heparin in the prehospital setting. The Assessment of the Safety and Efficacy of a New Thrombolytic Regimen (ASSENT)-3 PLUS Randomized Trial in Acute Myocardial Infarction. Circulation 2003;108:135-142.
- ASSENT-4 PCI Investigators. Primary versus tenecteplase-facilitated percutaneous coronary intervention in patients with ST-segment elevation acute myocardial infarction (ASSENT-4 PCI): randomised trial. Lancet 2006;367:569-578.