Author + information
- Steffen Desch, MD†∗ (, )
- Jochen Wöhrle, MD‡,
- Rainer Hambrecht, MD§,
- Harald Rittger, MD‖,
- Ralf Birkemeyer, MD¶,
- Bernward Lauer, MD#,
- Petra Neuhaus, PhD∗∗,
- Oana Brosteanu, PhD∗∗,
- Peter Sick, MD††,
- Matthias Pauschinger, MD‡‡,
- Sebastian Kerber, MD§§,
- Klaus Kleinertz, MD‖‖,
- Suzanne de Waha, MD†,
- Ingo Eitel, MD†,
- Gerhard Schuler, MD† and
- Holger Thiele, MD†
- †University of Leipzig Heart Center, Department of Internal Medicine/Cardiology, Leipzig, Germany
- ‡University of Ulm, Department of Internal Medicine/Cardiology, Ulm, Germany
- §Klinikum Links der Weser, Bremen, Germany
- ‖University of Erlangen, Department of Cardiology/Angiology, Erlangen, Germany
- ¶University of Rostock, Department of Cardiology, Rostock, Germany
- #Zentralklinik Bad Berka, Bad Berka, Germany
- ∗∗University Leipzig, Clinical Trial Center Leipzig, Leipzig, Germany
- ††Krankenhaus der Barmherzigen Brüder, Regensburg, Regensburg
- ‡‡Klinikum Nürnberg, Nürnberg, Germany
- §§Herz-und Gefäß-Klinik, Bad Neustadt, Bad Neustadt, Germany
- ‖‖Ambulantes Herzzentrum Chemnitz, Chemnitz, Germany
- ↵∗University of Leipzig Heart Center, Department of Internal Medicine/Cardiology, Strümpellstrasse 39, 04289 Leipzig, Germany
To the Editor:
In patients with ST-segment elevation myocardial infarction (STEMI), direct intracoronary as compared with standard intravenous bolus administration of the glycoprotein IIb/IIIa receptor antagonist abciximab acutely causes higher local drug concentrations, greater glycoprotein IIb/IIIa receptor occupancy, and enhanced inhibition of platelet aggregation at the site of thrombus and downstream within the coronary capillary bed (1). These effects might exert a protective effect on the myocardial microcirculation at the time of reperfusion.
At short-term follow-up (90 days), the largest randomized trial to date (AIDA STEMI [Abciximab Intracoronary Versus Intravenously Drug Application in STEMI]) comparing intracoronary and intravenous abciximab bolus application in patients with STEMI undergoing primary percutaneous coronary intervention (PCI) could not show a significant difference in a composite major adverse cardiac events endpoint, mortality, reinfarction, or bleeding between the 2 delivery routes (2). However, there were significantly fewer episodes of new congestive heart failure in patients randomized to intracoronary abciximab bolus administration. The present analysis reports 12 months of clinical results of the AIDA STEMI trial.
In brief, AIDA STEMI randomized 2,065 patients with acute STEMI undergoing primary PCI to either intracoronary or intravenous abciximab bolus application with subsequent 12-h intravenous infusion. All patients received dual oral antiplatelet therapy (aspirin and either clopidogrel or prasugrel). The primary endpoint was a composite of all-cause death, reinfarction, or new congestive heart failure at 90 days.
For the predefined 12-month follow-up, the primary analysis was performed for all patients who underwent randomization and had follow-up information according to the intention-to-treat principle. Predeﬁned subgroup analyses were performed for patient age, infarct location, Killip class, post-procedural Thrombolysis In Myocardial Infarction (TIMI) flow, time from symptom onset to randomization, and thrombectomy versus no thrombectomy. Exploratory post hoc analyses were performed for: 1) TIMI risk score of <5 versus ≥5; and 2) prasugrel versus no prasugrel comedication.
Of the 2,065 patients enrolled, 1,876 patients underwent short-term clinical follow-up at 90 days, whereas 189 patients were excluded for reasons previously outlined (2). At 12 months, follow-up was available for 1,846 patients (intracoronary group 925; intravenous group 921; 98.4% follow-up rate relative to the 90-day landmark). Baseline characteristics were well matched between groups. The composite endpoint of death, reinfarction, and new congestive heart failure was not significantly different between patients assigned to intracoronary versus intravenous abciximab bolus administration (Table 1). A total of 51 patients (5.5%) had died in the intracoronary compared with 42 (4.6%) in the intravenous group (p = 0.39) (Table 1). At the 90-day landmark, more episodes of new congestive heart failure in patients randomized to intravenous abciximab had been observed, albeit at a p value of 0.04 only on the verge of statistical significance (2). At 12 months, the observed numerical difference in event rates proved to be no longer significantly different (p = 0.07), supporting the hypothesis that this finding is most likely due to chance. Consistent with the overall cohort, predefined as well as post hoc analyses revealed no significant differences in results across a wide range of subgroups with regard to the combined endpoint of death, reinfarction, and new congestive heart failure with the exception of female patients, who seemed to benefit from intracoronary bolus administration (odds ratio: 0.55; 95% Confidence Interval: 0.33 to 0.91).
The results of the present analysis suggest that in patients with acute STEMI undergoing primary PCI and treated with dual oral antiplatelet therapy, direct intracoronary compared with standard intravenous bolus administration of abciximab does not result in significant differences with regard to hard clinical endpoints. This might seem surprising given previous data that direct intracoronary compared with intravenous abciximab bolus administration was associated with a variety of beneficial effects on surrogate markers in patients with STEMI. Several considerations may serve to explain these findings. First, despite being the largest trial studying intracoronary abciximab administration to date, AIDA STEMI might have been underpowered to detect small differences in clinical endpoints. Second, AIDA STEMI used an “all-comers” design. However, it is possible that intracoronary abciximab might only be advantageous in selected patients such as those with large thrombus burden, total occlusion, or reduced flow. AIDA STEMI subgroup analyses, however, do not support a selective benefit of intracoronary over intravenous bolus abciximab in high-risk patients. Third, the magnitude of the short-lived local effect of intracoronary abciximab might not be enough to produce changes in clinically meaningful endpoints, especially in the era of routine preloading with other potent antiplatelet agents. Fourth, in the AIDA STEMI trial, abciximab was injected through the guiding catheter after wiring of the infarct-related artery. Although easy to implement in clinical practice, this way of delivery might be suboptimal in selected patients because of inadequate thrombus penetration of abciximab and possible retrograde washout into the ascending aorta. Novel application systems such as dedicated perfusion catheters might exert superior efficacy by allowing high local drug concentrations in both vessel lumen and wall at the site of thrombus with prolonged focal dwelling times (3).
In conclusion, AIDA STEMI does not support a possible clinical superiority of intracoronary bolus delivery. (Abciximab IV Versus IC in ST-Elevation Myocardial Infarction [AIDA STEMI]; NCT00712101)
Please note: The study was sponsored by the University of Leipzig, Heart Center and the University of Leipzig, Clinical Trial Center, which is supported by the Bundesministerium fur Bildung und Forschung. Drs. Desch and Thiele received an unrestricted research grant from Eli Lilly. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.
- American College of Cardiology Foundation