EMPIRE: Exenatide Cardioprotective in STEMI Patients Receiving DES

LOS ANGELES, CA—The experimental agent exenatide appears cardioprotective in patients with ST-segment elevation myocardial infarction (STEMI) undergoing percutaneous coronary intervention (PCI), reducing infarct size and preserving left ventricular (LV) function, according to results of a small, randomized trial presented November 5, 2012, at the American Heart Association Scientific Sessions.

Exenatide is a glucagon-like peptide-1 (GLP-1) marketed as Byetta (Amylin Pharmaceuticals, San Diego, CA) for the treatment of type 2 diabetes. Previous small studies have shown the gut hormone analog to exert cardioprotective effects in STEMI patients. 

For the Exenatide Myocardial Protection In REvascularization (EMPIRE) trial, Sang Jin Ha, MD, of Kyung Hee University Hospital (Seoul, South Korea), and colleagues randomized 58 STEMI patients presenting within 12 hours at their institution to exenatide (n = 18) or placebo (n = 40). All patients underwent primary PCI with DES.

 The primary endpoint of infarct size at 1 month was reduced with exenatide as measured by cardiac MRI (table 1).

Table 1. Infarct Size at 1 Month on Cardiac MRI

Similar reductions were seen with exenatide in CK-MB levels at 6 to 18 hours (P < 0.05) and in troponin I levels from 12 to 48 hours (P < 0.05).

At 3 days, serial echocardiography showed equivalent ejection fraction between the exenatide (56.6%) and control groups (55.3%; P = 0.53), but global longitudinal strain (-17.6% vs. -15.1%; P = 0.004) and global longitudinal strain rate (-0.9 S^-1 vs. -0.8 S^-1; P = 0.006) were improved in the exenatide group.

At 6 months, ejection fraction was still similar between groups (P = 0.25), while other measures continued to show improvement with exenatide (table 2).

Table 2. Serial Echocardiography at 6 Months

Abbreviation: E/E’, ratio of mitral peak velocity of early filling to early diastolic mitral annular velocity.

In terms of cardiac biomarkers, CRP levels were lower at 1 month in exenatide patients (P = 0.02), while NT-proBNP levels were similar between the 2 groups (P = 0.61).

In terms of adverse effects, both diabetics and nondiabetics taking exenatide showed higher levels of nausea (P = 0.001) and vomiting (P = 0.002) than controls, while only nondiabetics taking exenatide showed more loss of appetite than controls (31% vs. 0; P = 0.002). Other adverse effects such as hypoglycemia, elevated creatinine level, and diarrhea were low and equivalent between groups.

Dr. Ha called the small study a “proof-of-concept” trial, with exenatide patients achieving reduced infarct size, reduced systemic inflammation, and preserved LV filling pressure with improving echocardiographic parameters during the chronic phase compared with controls. He acknowledged the small study sample and the lack of enrolled patients with systolic dysfunction. In addition, the mechanism for decreased CRP levels needs to be clarified.

Nevertheless, “Adjunctive exenatide therapy in the acute phase may reduce myocardial infarct size and improve subclinical LV systolic function with reasonable safety/tolerability,” Dr. Ha concluded.

Study Details

All patients had total occlusion of the culprit coronary artery (TIMI flow grade 0). Baseline characteristics were similar between the 2 groups, as were lesion type and disease severity. Exenatide was given as 10 µg subcutaneous and 10 µg IV 5 minutes before onset of reperfusion, then 10 µg subcutaneous twice daily for following 2 days.

Source:

Ha SJ. Cardioprotective effects of exenatide in patients with ST-segment elevation myocardial infarction undergoing primary percutaneous coronary intervention. Results of the Exenatide Myocardial Protection In REvascularization (EMPIRE) study. Presented at: American Heart Association Scientific Sessions; November 5, 2012; Los Angeles, CA.

Disclosure:

• Dr. Ha reports no relevant conflicts of interest.

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