Pexelizumab for acute ST-elevation myocardial infarction in patients undergoing primary percutaneous coronary
1, Paul W Armstrong, Christopher B Granger
1University of Alberta, Edmonton, Alberta, T6G 2H7 Canada. paul.armstrong@ualberta.ca
Insights
Pexelizumab did not reduce 30-day mortality in patients with ST-elevation myocardial infarction (STEMI) treated with percutaneous coronary intervention (PCI). This large trial found no significant difference in mortality or composite endpoints between pexelizumab and placebo groups.
Area of Science:
- Cardiology
- Immunology
- Pharmacology
Background:
- Percutaneous transluminal coronary intervention (PCI) improves outcomes for ST-elevation myocardial infarction (STEMI) patients.
- High mortality persists in STEMI patients without rapid reperfusion, indicating a need for novel treatments like anti-inflammatory agents.
Purpose of the Study:
- To evaluate pexelizumab, a C5 complement inhibitor, as an adjunct to PCI in reducing 30-day mortality in STEMI patients.
Main Methods:
- A prospective, multicenter, double-blind, placebo-controlled phase 3 trial involving 5745 STEMI patients undergoing primary PCI.
- Patients received either pexelizumab or placebo intravenously prior to PCI, with a 24-hour infusion.
- The primary endpoint was all-cause mortality at 30 days.
Main Results:
- No significant difference in 30-day all-cause mortality was observed between the pexelizumab (4.06%) and placebo (3.92%) groups (HR, 1.04; 95% CI, 0.80-1.35).
- Composite endpoints including death, cardiogenic shock, or heart failure at 30 and 90 days were also similar between groups.
- Mortality rates were low in both treatment arms.
Conclusions:
- Pexelizumab administration did not affect mortality in STEMI patients treated with primary PCI.
- The study demonstrated low mortality in this high-risk STEMI population.
- Further investigation into adjunctive therapies for STEMI may be warranted.
Context:
Reperfusion with percutaneous transluminal coronary intervention (PCI) is effective at improving outcomes in patients with acute ST-elevation myocardial infarction (STEMI). However, in patients without prompt reestablishment of brisk coronary flow and tissue perfusion, mortality remains high, providing an opportunity for novel treatments, including anti-inflammatory agents.
Objective:
To evaluate the effectiveness of pexelizumab, a humanized monoclonal antibody that binds the C5 component of complement, as an adjunct to PCI in improving 30-day mortality from STEMI.
Design, Setting, And Patients:
This trial was a prospective, multicenter, double-blind, placebo-controlled, phase 3 study of the intravenous administration of pexelizumab in conjunction with primary PCI in STEMI with prespecified high-risk electrocardiographic findings. The trial was intended to enroll 8500 patients, but in conjunction with the US Food and Drug Administration enrollment was modified to 5745 patients presenting from 296 hospitals in 17 countries from July 13, 2004, to May 11, 2006.
Interventions:
Two thousand eight hundred eighty-five patients were randomly assigned to receive placebo and 2860 to receive pexelizumab given as a 2-mg/kg intravenous bolus prior to PCI followed by 0.05-mg/kg per hour infusion over the subsequent 24 hours. Patients were randomized within 6 hours of symptom onset.
Main Outcome Measures:
The primary end point was all-cause mortality through day 30. Secondary end points were death through day 90 and the composite of death, cardiogenic shock, or congestive heart failure through days 30 and 90.
Results:
No difference in mortality through day 30 was observed between the pexelizumab and placebo treatment groups, with 116 patients (4.06%) and 113 patients (3.92%) who died in the respective groups (hazard ratio [HR], 1.04; 95% confidence interval [CI], 0.80-1.35; log-rank P = .78). The composite end points of death, shock, or heart failure were also similar with 257 patients (8.99%) receiving pexelizumab and 265 patients (9.19%) receiving placebo at 30 days (HR, 0.98; 95% CI, 0.83-1.16; P = .81) and 293 patients (10.24%) receiving pexelizumab and 293 patients (10.16%) receiving placebo at 90 days (HR, 1.01; 95% CI, 0.86-1.19; P = .91).
Conclusion:
In this large clinical trial of patients treated with primary PCI for STEMI, mortality was low and unaffected by administration of pexelizumab.
Trial Registration:
clinicaltrials.gov Identifier: NCT00091637.
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