Intracoronary alteplase was not superior to placebo in reducing the composite of MACE, MBG 0/1, distal embolization, or failure of ST-segment resolution (RR 1.00; 95% CI 0.76-1.31; P>0.99).
RCT (n=210)
double-blind
randomized
Yes
Does adjunctive intracoronary delivery of low-dose alteplase reduce microvascular obstruction or major adverse cardiovascular events in patients undergoing primary PCI for STEMI and high thrombus burden?
Intracoronary administration of low-dose alteplase during primary PCI for STEMI with large thrombus burden does not improve microvascular obstruction or 30-day clinical outcomes and may increase the risk of ventricular fibrillation.
Effect estimate: RR 1.00 (95% CI 0.76-1.31)
Absolute Event Rate: 53.3% vs 52.9%
p-value: p=>0.99
BACKGROUND In patients with ST-segment elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PCI), about one-half of patients experience distal embolization of thrombus causing microvascular obstruction and reduced myocardial tissue perfusion. Targeted, intracoronary delivery of low-dose recombinant tissue plasminogen activator (alteplase) might be an effective strategy for improving microvascular obstruction without increasing the risk of systemic bleeding. OBJECTIVE To determine whether adjunctive intracoronary delivery of low dose alteplase reduces microvascular obstruction or major adverse cardiovascular events (MACE) in patients undergoing primary PCI for STEMI and high thrombus burden. METHODS We performed a multicenter, randomized, double-blind trial involving patients undergoing primary PCI for large territory STEMI and high thrombus burden. Patients were randomized to receive either alteplase 10 mg, alteplase 20 mg or placebo (saline) administered directly into the infarct-related artery using a delivery catheter, after antegrade reperfusion was established. The primary outcome was the composite of major adverse cardiovascular events (MACE), myocardial blush grade (MBG) 0/1, distal embolization or failure to achieve ≥ 50% ST-segment resolution at 30 minutes post-PCI. MACE was the composite of cardiovascular death, myocardial re-infarction, cardiogenic shock or new onset heart failure at 30 days. RESULTS Of the 210 patients that were randomized, 207 received study drug (68 alteplase 10 mg, 69 alteplase 20 mg and 70 placebo). The mean age was 62.6 years and 25% were female. The median time from symptom onset to randomization was 2.9 hours. The primary outcome occurred in 73 patients (53.3%) in the combined alteplase groups versus 37 (52.9%) in the placebo group (relative risk 1.00, 95 % CI 0.76-1.31, P>0.99). Results were consistent across all components of the primary outcome and for each dose group versus placebo. Major or clinically significant bleeding occurred in 1 patient in the trial (in the alteplase 20 mg group). During study drug administration, there was a trend to more episodes of ventricular fibrillation in the alteplase groups compared with the placebo group (10.2% vs 1.4%, relative risk 6.86, 95% CI 0.91-51.4, P=0.06). CONCLUSION Among patients undergoing primary PCI for STEMI and large thrombus burden, intracoronary administration of alteplase was not superior to placebo in reducing the composite primary outcome of MACE at 30 days, MBG 0/1, distal embolization or failure to achieve ≥ 50% ST-segment resolution. These data do not support the routine administration of this therapy in patients with STEMI undergoing primary PCI. (clinicaltrials.gov NCT03335839).
“We could not have any more of a neutral result. Regardless of how you look at microvascular obstruction, whether you look at it angiographically with myocardial blush grade or whether you look at it with ST-segment resolution at 30 minutes, it is completely neutral.”
Mehta et al. (Tue,) conducted a rct in ST-segment elevation myocardial infarction (STEMI) and large thrombus burden (n=210). alteplase vs. placebo (saline) was evaluated on composite of major adverse cardiovascular events (MACE), myocardial blush grade (MBG) 0/1, distal embolization or failure to achieve ≥ 50% ST-segment resolution at 30 minutes post-PCI (RR 1.00, 95% CI 0.76-1.31, p=>0.99). Intracoronary alteplase was not superior to placebo in reducing the composite of MACE, MBG 0/1, distal embolization, or failure of ST-segment resolution (RR 1.00; 95% CI 0.76-1.31; P>0.99).