Intracoronary Abciximab Shows Advantage in Diabetic STEMI Patients

Intracoronary administration of abciximab during primary PCI in diabetic patients with STEMI may enhance procedural efficacy and improve clinical outcomes, a pooled patient-level analysis indicates. 

Intracoronary abciximab has been fraught with controversy in recent years. The randomized, multicenter, large-scale AIDA-STEMI trial, which compared intracoronary and intravenous administration, failed to show a reduction in death or MI with the intracoronary route despite the suggestion that high drug load and immediate onset of action at the culprit site may be more efficacious.

In the new study, published online August 8, 2016, ahead of print in Journal of the American College of Cardiology, researchers led by Raffaele Piccolo, MD (Bern University Hospital, Bern, Switzerland), examined data on 2,470 patients (19% with diabetes) treated either as part of AIDA-STEMI or in two other single-center investigations in which patients were randomized to intracoronary or intravenous abciximab bolus at time of primary PCI.

Compared with those who received intravenous therapy, diabetic patients who received intracoronary abciximab had lower rates of all-cause death or reinfarction, the primary endpoint, at 1 year (HR 0.49; 95% CI 0.28-0.83). The benefit was also seen in the first 30 days. In addition, the intracoronary cohort had a lower risk of all-cause death (HR 0.51; 95% CI 0.26-0.98) and definite/probable stent thrombosis (HR 0.27; 95% CI 0.08-0.98).

However, risk of the primary endpoint were unaffected by intracoronary abciximab in those without diabetes. Similarly, diabetic patients who received intracoronary versus intravenous drug therapy had increased myocardial salvage index on cardiac magnetic resonance imaging that was not seen in nondiabetic patients; no differences were seen with respect to infarct size, microvascular obstruction, and LVEF after treatment.

“The identification of diabetic patients as potential candidates who can benefit to a greater extent from an intracoronary bolus of abciximab during primary PCI may have important implications, because diabetes is present in approximately one-third of patients undergoing PCI and conveys a high residual risk after myocardial revascularization,” Piccolo and colleagues write.

Suggestive of a Chance Finding

But in an accompanying editorial, José P.S. Henriques, MD, PhD and Wouter J. Kikkert, MD, PhD (University of Amsterdam, the Netherlands), express several concerns about the findings. Chief among these is that the pooled analysis was grossly underpowered to detect a difference in mortality, let alone stent thrombosis, and may be a “chance finding.”

To TCTMD, Piccolo acknowledged that the study was not adequately powered. He noted that while he and his colleagues consider the results to be hypothesis generating, and the risk of a false positive finding is possible, the potential benefit of intracoronary abciximab among diabetic patients was substantiated not solely by an isolated finding but rather by several converging observations.

“If we consider bleeding as a falsification endpoint, the similar rate of bleeding among diabetic patients randomized to intracoronary versus intravenous abciximab bolus indirectly unveils the equivalent risk profile of the two groups,” Piccolo said. “Finally, a wealth of data . . . from studies of novel P2Y12 receptor inhibitors (ie, prasugrel and ticagrelor) to protease-activated receptor-1 antagonists (ie, vorapaxar) have shown that more potent antithrombotic therapy conveys a greater absolute or even relative benefit in diabetic compared with nondiabetic patients.”

However, Henriques, Kikker, and even JACC Editor-in-Chief Valentin Fuster, MD, PhD (Mount Sinai School of Medicine, New York, NY), who posted audio commentary about the article on the journal’s website, question how change in myocardial salvage index with no corresponding reduction in infarct size or improvement in LVEF can explain the mortality reduction seen with abciximab.

In response, Piccolo said several studies have demonstrated that myocardial salvage index is a powerful correlate of mortality and major adverse cardiac events, even after adjustment for infarct size.

“Although infarct size remains the biological target of any adjuvant therapy in the setting of STEMI, its final therapeutic benefit depends on a variety of factors, including the extent of area at risk, duration of ischemia, collateral blood flow, and metabolic demand,” he said. “Furthermore, when the study is small, the myocardial salvage index is a better surrogate than infarct size due to its greater statistical power.”

Finally, Henriques and Kikker caution that glycoprotein IIb/IIIa inhibitor therapy “has consistently been associated with severe bleeding complications (when compared with placebo).” Since the benefit is questionable when added to current STEMI treatment, they say, “we will need adequately powered trials randomizing patients with diabetes and STEMI to either intracoronary abciximab or placebo before we can adopt this treatment into clinical practice.”

Disclosures:

• Piccolo reports a research grant from the Veronesi Foundation. 
• Henriques and Kikkert report no relevant conflicts of interest. 

Related Stories:

• INFUSE-AMI: Bolus Abciximab Works, Thrombus Aspiration Doesn’t for Large STEMI
• AIDA STEMI: No Advantage for Intracoronary vs. Intravenous Abciximab
• Meta-analysis: Intracoronary vs. IV Abciximab Improves Survival in STEMI Patients