Clinical outcomes of intracoronary eptifibatide bolus only versus intracoronary bolus and intravenous infusion of eptifibatide in primary percutaneous coronary intervention

Abstract

Intracoronary bolus of eptifibatide during percutaneous coronary intervention (PCI) for acute myocardial infarction (AMI) has been shown to result in higher local platelet glycoprotein IIb/IIIa receptor occupancy with improved microvascular perfusion. It is unclear whether intracoronary administration of eptifibatide in a larger patient population results in favourable clinical outcomes. We evaluated the safety and efficacy of two regimens of intracoronary eptifibatide (bolus only versus bolus followed by intravenous infusion) in patients undergoing primary PCI for ST-elevation MI. They were divided into two groups: Group A (n =  67) who received fixed-dose intracoronary eptifibatide bolus only and Group B (n =  88) who received intracoronary bolus and continuous intravenous infusion of eptifibatide for 18 h. The preliminary findings from our registry showed that both regimens were associated with good angiographic outcomes, few bleeding events and low in-hospital major adverse cardiac events. A large prospective randomized, multi-centre trial is needed to confirm our observation.

Keywords::

• Eptifibatide
• intracoronary
• primary percutaneous coronary intervention
• myocardial infarction

Introduction

Embolization of atherothrombotic material is common during primary percutaneous coronary intervention (PCI) of patients presenting with ST-elevation myocardial infarction (STEMI). This may lead to distal vessel occlusion resulting in impaired myocardial perfusion (1), which is associated with larger infarct size and adverse clinical outcomes. Intracoronary bolus of eptifibatide during PCI for acute myocardial infarction (AMI) has been shown by a preliminary study (2) to result in higher platelet glycoprotein IIb/IIIa (GPIIb/IIIa ) receptor occupancy with improved microvascular perfusion. However, it is unclear whether intracoronary administration of eptifibatide in a larger patient population results in favourable clinical outcomes.

Methods

We evaluated the safety and efficacy of two regimens of intracoronary eptifibatide (bolus only versus bolus followed by intravenous infusion) in 155 patients undergoing primary PCI for STEMI at our institution from the period January to July 2010. They were divided into two groups: Group A (n =  67) who received fixed-dose intracoronary eptifibatide bolus only (180 µg/kg) and Group B (n =  88) who received intracoronary bolus (180 µg/kg) and continuous intravenous infusion of eptifibatide (2 µg/kg/min) for 18 h. The intracoronary eptifibatide bolus was administered twice in both regimens with the second bolus given 10 min after the first bolus. All patients were front loaded with oral aspirin 300 mg and clopidogrel 600 mg before the procedure. They all received dual antiplatelet therapy after the procedure; aspirin 100 mg daily indefinitely and clopidogrel 75 mg daily for at least one month to one year, depending on type of stent implanted and clinical decision of the attending physician. All PCIs were performed using standard techniques and unfractionated heparin (70 units/kilogram) was administered in all cases to maintain an activated clotting time of 200 to 300 s. The adjunctive intracoronary eptifibatide regimen was given routinely peri-procedurally (whether A or B regimen was upon the operator's discretion). The major clinical outcomes analysed were in-hospital mortality, target-lesion revascularization, stent thrombosis and bleeding complications. Continuous variables and categorical variables were expressed as mean ± standard deviation and percentages, respectively. Statistical comparisons of demographic and clinical variables between the two groups were performed using chi-square test and Fisher's exact test as appropriate.

Results

The clinical characteristics, angiographic findings, procedural variables and clinical outcomes of patients in both groups are summarized in Tables I and II respectively. Both groups had similar baseline clinical characteristics except patients in Group B had a higher incidence of prior AMI (11.4% versus 1.5% in Group A, P =  0.02). Both groups (>  68%) were equally likely to undergo PCI with implantation of stents (predominantly bare metal stents). However, plain old balloon angioplasty (POBA) was more often performed in Group B (21.6% versus 6% in Group A, P =  0.01). Post PCI thrombolysis in myocardial infarction (TIMI) 3 flow was achieved in 97% and 92% of patients in Group A and B respectively (P =  0.3). Overall in-hospital mortality was 3.2% (5 patients) and did not differ between both groups (1.5% in Group A versus 4.5% in Group B, P =  0.4). No significant difference was observed for both groups in terms of target lesion revascularization and stent thrombosis. There was only one major bleeding complication with patient from Group A developing a large groin haematoma (>  5cm) post PCI. 4 cases (6%) and 6 cases (7%) of minor bleeding events were observed in Group A and B respectively (P = NS).

Table I. Baseline clinical characteristics of patients.

	Overall (n =  155)	Bolus only (n =  67)	Bolus & infusion (n =  88)	P value
Mean age, years	55.4 ± 9.2 (29–80 years)	56.6 ± 8.5	54.5 ± 9.6	0.15
Sex: female:male, (%)	18:137 (11.6:88.4)	7:60 (10.4:89.6)	11:77 (12.5:87.5)	0.80
Hypertension, n (%)	71 (45.8)	32 (47.8)	39 (44.3)	0.74
Smoking, n (%)	88 (56.8)	36 (53.7)	52 (59.1)	0.51
Diabetes, n (%)	49 (31.6)	17 (25.5)	32 (36.4)	0.16
Hyperlipidaemia, n (%)	63 (40.6)	23 (34.3)	40 (45.5)	0.18
Prior MI, n (%)	11 (7.1)	1 (1.5)	10 (11.4)	0.02^a
Prior PCI, n (%)	12 (7.7)	3 (4.5)	9 (10.2)	0.23
Prior CABG, n (%)	1 (0.6)	1 (1.5)	0 (0)	0.43
LVEF (%, mean)	36.1 ± 19.6	37.0 ± 19.8	35.4 ± 19.6	0.62
Cardiogenic shock, n, %	27 (17.4)	10 (14.9)	17 (19.3)	0.52
Peak CK (IU/L, mean)	2896.7 ± 2381.9	2630.7 ± 1988	3105.6 ± 2644	0.22

MI, myocardial infarction; PCI, percutaneous coronary intervention; CABG, coronary artery bypass graft; LVEF, left ventricular ejection fraction; CK, creatine phosphokinase.

^aP value <  0.05.

Table II. Angiographic findings, procedural variables and clinical outcomes.

	Overall (n = 155)	Bolus only (n = 67)	Bolus & infusion (n = 88)	P value
Culprit vessel, n (%)
LAD, n (%)	77 (49.7)	33 (49.3)	44 (50.0)	1.0
RCA, n (%)	62 (40.0)	27 (40.3)	35 (39.8)	1.0
CIRC, n (%)	16 (10.3)	7 (10.4)	9 (10.2)	1.0
POBA, n (%)	23 (14.8)	4 (6.0)	19 (21.6)	0.01^a
Manual thrombus Aspiration, n (%)	135 (87.1)	56 (83.6)	79 (89.8)	0.33
Angiojet rheolytic thrombectomy, n (%)	6 (3.9)	1 (1.5)	5 (5.7)	0.23
TIMI flow (pre)
0, n (%)	129 (83.2)	53 (79.1)	76 (86.4)	0.30
1, n (%)	10 (6.5)	6 (9.0)	4 (4.5)	0.33
2, n (%)	14 (9.0)	8 (11.9)	6 (6.8)	0.39
3, n (%)	2 (1.3)	0 (0)	2 (2.3)	0.50
Final TIMI flow
0, n (%)	1 (0.6)	0 (0)	1 (1.1)	1.0
1, n (%)	1 (0.6)	0 (0)	1 (1.1)	1.0
2, n (%)	7 (4.5)	2 (3.0)	5 (5.7)	0.7
3, n (%)	146 (94.2)	65 (97.0)	81 (92.0)	0.3
Stents (total 132)	(n = 132)	(n = 63)	(n = 69)	0.45
BMS: DES, (n: %)	89: 43 (67.4: 32.6)	40: 23 (63.5: 36.5)	49: 20 (71: 29)
Death, n (%)	5 (3.2)	1 (1.5)	4 (4.5)	0.4
Target lesion revascularization, n (%)	1 (0.6)	0 (0)	1 (1.1)	1.0
Stent thrombosis, n (%)	1 (0.6)	0 (0)	1 (1.1)	1.0
Bleeding (overall), n (%)	11 (7.1)	5 (7.5)	6 (6.8)	1.0
Major bleeding, n (%)	1 (0.6)	1 (1.5)	0 (0)	1.0
Minor bleeding, n (%)	10 (6.5)	4 (6)	6 (6.8)	1.0

LAD, left anterior descending artery; RCA, right coronary artery; CIRC, left circumflex artery; POBA, plain old balloon angioplasty; TIMI, thrombolysis in myocardial infarction; BMS, bare metal stent; DES, drug eluting stent.

^aP value < 0.05.

Discussion

Primary PCI is now the preferred reperfusion therapy for patients with STEMI. Adjunctive use of GPIIb/IIIa inhibitors in patients undergoing PCI for AMI has been shown to reduce major adverse cardiac events besides improving microvascular circulation and facilitating the recovery of left ventricular function. Several studies (2,3) had shown that intracoronary administration of GPIIb/IIIa inhibitors greatly increase local drug concentration at the site of ruptured plaque when compared with systemic administration. This resulted in higher platelet GPIIb/IIIa receptor occupancy, which enhance platelet-rich thrombus disaggregation and improve microvascular perfusion. Intracoronary administration of abciximab (4) (another GPIIb/IIIa inhibitors) during primary PCI for patients with STEMI have been well studied. However, there is limited data on the clinical use of intracoronary eptifibatide in this context. In a non-randomized study (5), Pinto et al. evaluated the efficacy and clinical outcomes among 59 patients who received intracoronary eptifibatide before primary PCI for STEMI. They observed modest rates of normal myocardial perfusion (TIMI 3 flow in 54% of patients) after primary PCI with adjunctive intracoronary eptifibatide and no major adverse event was recorded. The findings of our ‘real world’ registry extend this previous observation in a much larger patient population. We demonstrated that intracoronary bolus of eptifibatide (with or without intravenous infusion) was safe and effective in STEMI patients undergoing primary PCI in the contemporary era in which patients were pre-treated with high dose clopidogrel. Both regimens were associated with good angiographic outcomes (TIMI 3 flow achieved >  90% of cases), few bleeding events and low in-hospital major adverse cardiac events.

NOTICE OF CORRECTION

The Early Online version of this article was published online ahead of print/online issue on 24 January 2012 without keywords. Keywords have now been added.

Declaration of interest: The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.