MISTRAL: No Lasting Benefit from Early Abciximab in STEMI Patients

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In patients with ST-segment elevation myocardial infarction (STEMI), administering abciximab in the ambulance is no better than delivering the drug upon arrival at the cath lab, concludes a paper published online February 7, 2012, ahead of print in Circulation: Cardiovascular Interventions. Early administration fails to improve the likelihood of complete ST-segment resolution after PCI; however, there are some signs that the strategy can improve preprocedural flow and reduce distal embolization during intervention.

For the double-blind MISTRAL (Myocardial Infarction with ST-elevation Treated by Primary Percutaneous Intervention Facilitated by Early Reopro Administration in Alsace) study, researchers led by Patrick Ohlmann, MD, PhD, of Nouvel Hôpital Civil (Strasbourg Cedex, France), randomized 256 consecutive STEMI patients to receive either the glycoprotein IIb/IIIa inhibitor (GPI) abciximab (n = 127) or placebo (n = 129) in the ambulance during transport. Patients in the placebo group received blinded therapy with abciximab in the cath lab just after angiography. Irrespective of timing, abciximab was given intravenously at a dose of 0.25 mg/kg in both groups.

Overall, the median time between symptom onset and first bolus was 114 minutes (interquartile range [IQR], 80-190 minutes), with the time difference between study groups amounting to 65 minutes (IQR, 54-78 minutes).

Complete ST-segment resolution (> 70%), the study’s primary endpoint, was similar regardless of when abciximab was administered, as was the prevalence of TIMI 2/3 flow after PCI. However, early abciximab appeared to temporarily improve TIMI flow before PCI and also led to decreases in slow flow and distal embolization during the procedure (table 1).

Table 1. MISTRAL: Main Results According to Abciximab Administration

Infarct size and biomarker levels were similar in both groups during the index hospitalization. The rates of major adverse cardiac events including death, MI, and TVR were equivalent at 11% in each group while major bleeding occurred in 0.8% of the ambulance group and 1.6% of the cath lab group.

Despite the largely negative results, “[a]bciximab given very early in the course of STEMI might facilitate primary PCI by improving the visibility of the coronary anatomy, thus allowing a faster and more-accurate procedure,” Dr. Ohlmann and colleagues note, adding that larger studies should be conducted to confirm this hypothesis.

In an e-mail communication with TCTMD, Dr. Ohlmann seemed encouraged by the secondary findings suggesting an increase in preprocedural TIMI flow from early abciximab but cautioned that the study was underpowered to detect significant differences in this endpoint.

“We might reserve [the ambulance-based] strategy for high risk STEMI (anterior location, high ST elevation) presenting early (< 2 hours), and with low bleeding risk,” he advised.

Limited Applicability

Sorin J. Brener, MD, of Weill Cornell Medical College (New York, NY), told TCTMD in a telephone interview that because of logistic barriers, in-ambulance abciximab is unlikely to be used in the United States. Even within Europe, he said, early use of the drug is only popular in France, where physicians are present during transfer.

The FINESSE trial, published in the New England Journal of Medicine in 2008, found that early abciximab added to primary PCI does not improve 90-day clinical outcomes over what could be achieved by giving the drug in the cath lab. After those results came to light, “pretty much everyone moved away from this idea of facilitated angioplasty,” Dr. Brener said, adding that the current study is unlikely to change that.

According to Dr. Ohlmann et al, FINESSE has been criticized for having a 165-minute median delay between symptom onset and drug administration. MISTRAL shortened that lag to a median of 103 minutes, but in doing so may have muted any difference between the 2 treatment groups, Dr. Brener observed.

Dr. Brener noted that timing of abciximab in the current study is much like that of the ON-TIME-2 trial, which found that giving a high-dose bolus of tirofiban to STEMI patients in the ambulance before primary PCI improved ST-segment resolution and short-term clinical outcomes.

ON-TIME-2, published in the Lancet in 2008, tested “very early” GPI use, with a 76-minute median interval between symptom onset and tirofiban administration, Dr. Ohlmann and colleagues point out. “Therapeutic intervention in the so-called ‘golden hours’ of myocardial reperfusion was also associated with significant prehospital benefits” much like MISTRAL, they say.

But these short-term advantages may not be worth the price, countered Dr. Brener. “Obviously the reasons that we weren’t any more enamored with [early GPI use] are that it causes more bleeding and you wind up giving [the drugs] to people who do not need them if you don’t do angioplasty.”

Moreover, the equivalent rates of direct stenting at 50% in the ambulance group and 43% of the cath lab group (P = 0.55) undermine the idea that improved patency can facilitate procedures, Dr. Brener concluded.

 

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Source:
Ohlmann P, Reydel P, Jacquemin L, et al. Prehospital abciximab in ST-segment elevation myocardial infarction: Results of the randomized, double-blind MISTRAL study. Circ Cardiovasc Interv. 2012;5:69-76.

 

 

Related Stories:

• On-TIME 2 Published: Early Tirofiban Improves PCI Outcomes in STEMI Patients
• ON-TIME: Prehospital Tirofiban Improves Outcome of Primary PCI
• FINESSE Published: Facilitated PCI No Improvement Over Primary PCI