Eptifibatide Drug Information
Generic name: EPTIFIBATIDE
Platelet Aggregation Inhibitor [EPC]
Uses of Eptifibatide
Acute Coronary Syndrome (ACS)
Eptifibatide injection is indicated to decrease the rate of a combined endpoint of death or new myocardial infarction (MI) in patients with ACS (unstable angina /non-ST-elevation myocardial infarction ), including patients who are to be managed medically and those undergoing percutaneous coronary intervention (PCI).
Percutaneous Coronary Intervention (PCI)
Eptifibatide injection is indicated to decrease the rate of a combined endpoint of death, new MI, or need for urgent intervention in patients undergoing PCI, including those undergoing intracoronary stenting.
Dosage & Administration of Eptifibatide
Dosage in Percutaneous Coronary Intervention (PCI)
Eptifibatide injection should be given concomitantly with heparin to achieve a target ACT of 200 to 300 seconds. Administer 60 units/kg bolus initially in patients not treated with heparin within 6 hours prior to PCI. Additional boluses during PCI to maintain ACT within target.
Heparin infusion after the PCI is strongly discouraged. Patients requiring thrombolytic therapy should discontinue eptifibatide injection.
Important Administration Instructions
Inspect eptifibatide injection for particulate matter and discoloration prior to administration, whenever solution and container permit. May administer eptifibatide injection in the same intravenous line as alteplase, atropine, dobutamine, heparin, lidocaine, meperidine, metoprolol, midazolam, morphine, nitroglycerin, or verapamil. Do not administer eptifibatide injection through the same intravenous line as furosemide.
May administer eptifibatide injection in the same I.V. line with 0.9% NaCl or 0.9% NaCl/5% dextrose. With either vehicle, the infusion may also contain up to 60 mEq/L of potassium chloride. Withdraw the bolus dose(s) of eptifibatide injection from the 10 mL vial into a syringe.
Administer the bolus dose(s) by I.V. push. Immediately following the bolus dose administration, initiate a continuous infusion of eptifibatide. When using an intravenous infusion pump, administer eptifibatide injection undiluted directly from the 100 mL vial.
Spike the 100 mL vial with a vented infusion set. Center the spike within the circle on the stopper top. Discard any unused portion left in the vial.
Administer eptifibatide injection by volume according to patient weight (see Table 1). Table 1: Eptifibatide Injection Dosing Charts by Weight
| Indication | Normal Renal Function | Creatinine Clearance less than 50 mL/min |
|---|---|---|
| Patients with ACS | 180 mcg/kg intravenous (I.V.) bolus as soon as possible after diagnosis, followed by continuous infusion of 2 mcg/kg/min | 180 mcg/kg I.V. bolus as soon as possible after diagnosis, followed by continuous infusion of 1 mcg/kg/min |
| Infusion should continue until hospital discharge or initiation of coronary artery bypass graft surgery (CABG), up to 72 hours If a patient is to undergo PCI, the infusion should be continued until hospital discharge or for up to 18 to 24 hours after the procedure, whichever comes first, allowing for up to 96 hours of therapy Aspirin, 160 to 325 mg, should be given daily | ||
| Indication | Normal Renal Function | Creatinine Clearance less than 50 mL/min |
|---|---|---|
| Patients with PCI | 180 mcg/kg I.V. bolus immediately before PCI followed by continuous infusion of 2 mcg/kg/min and a second bolus of 180 mcg/kg (given 10 minutes after the first bolus) | 180 mcg/kg I.V. bolus immediately before PCI followed by continuous infusion of 1 mcg/kg/min and a second bolus of 180 mcg/kg (given 10 minutes after the first bolus) |
| Infusion should be continued until hospital discharge, or for up to 18 to 24 hours, whichever comes first. A minimum of 12 hours of infusion is recommended. In patients who undergo CABG surgery, eptifibatide infusion should be discontinued prior to surgery. Aspirin, 160 to 325 mg, should be given 1 to 24 hours prior to PCI and daily thereafter. | ||
| Patient Weight | 180 mcg/kg Bolus Volume | 2 mcg/kg/min Infusion Volume (CrCl greater than or equal to 50 mL/min) | 1 mcg/kg/min Infusion Volume (CrCl less than 50 mL/min) | |||
|---|---|---|---|---|---|---|
| (kg) | (lb) | (from 2 mg/mL vial) | (from 2 mg/mL 100 mL vial) | (from 0.75 mg/mL 100 mL vial) | (from 2 mg/mL 100 mL vial) | (from 0.75 mg/mL 100 mL vial) |
| 37 to 41 | 81 to 91 | 3.4 mL | 2 mL/h | 6 mL/h | 1 mL/h | 3 mL/h |
| 42 to 46 | 92 to 102 | 4 mL | 2.5 mL/h | 7 mL/h | 1.3 mL/h | 3.5 mL/h |
| 47 to 53 | 103 to 117 | 4.5 mL | 3 mL/h | 8 mL/h | 1.5 mL/h | 4 mL/h |
| 54 to 59 | 118 to 130 | 5 mL | 3.5 mL/h | 9 mL/h | 1.8 mL/h | 4.5 mL/h |
| 60 to 65 | 131 to 143 | 5.6 mL | 3.8 mL/h | 10 mL/h | 1.9 mL/h | 5 mL/h |
| 66 to 71 | 144 to 157 | 6.2 mL | 4 mL/h | 11 mL/h | 2 mL/h | 5.5 mL/h |
| 72 to 78 | 158 to 172 | 6.8 mL | 4.5 mL/h | 12 mL/h | 2.3 mL/h | 6 mL/h |
| 79 to 84 | 173 to 185 | 7.3 mL | 5 mL/h | 13 mL/h | 2.5 mL/h | 6.5 mL/h |
| 85 to 90 | 186 to 198 | 7.9 mL | 5.3 mL/h | 14 mL/h | 2.7 mL/h | 7 mL/h |
| 91 to 96 | 199 to 212 | 8.5 mL | 5.6 mL/h | 15 mL/h | 2.8 mL/h | 7.5 mL/h |
| 97 to 103 | 213 to 227 | 9 mL | 6 mL/h | 16 mL/h | 3 mL/h | 8 mL/h |
| 104 to 109 | 228 to 240 | 9.5 mL | 6.4 mL/h | 17 mL/h | 3.2 mL/h | 8.5 mL/h |
| 110 to 115 | 241 to 253 | 10.2 mL | 6.8 mL/h | 18 mL/h | 3.4 mL/h | 9 mL/h |
| 116 to 121 | 254 to 267 | 10.7 mL | 7 mL/h | 19 mL/h | 3.5 mL/h | 9.5 mL/h |
| >121 | >267 | 11.3 mL | 7.5 mL/h | 20 mL/h | 3.7 mL/h | 10 mL/h |
Side Effects of Eptifibatide
Clinical Trials Experience
Because clinical studies are conducted under widely varying conditions, adverse reaction rates observed in the clinical studies of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in clinical practice. A total of 16,782 patients were treated in the Phase III clinical trials (PURSUIT, ESPRIT, and IMPACT II). Eighty-nine percent of the patients were Caucasian, with the remainder being predominantly Black (5%) and Hispanic (5%).
Sixty-eight percent were men. Because of the different regimens used in PURSUIT, IMPACT II, and ESPRIT, data from the 3 studies were not pooled. Bleeding and hypotension were the most commonly reported adverse reactions (incidence ≥5% and greater than placebo) in the eptifibatide controlled clinical trial database.
Bleeding The incidence of bleeding and transfusions in the PURSUIT and ESPRIT studies are shown in Table 2. Bleeding was classified as major or minor by the criteria of the TIMI study group. Major bleeding consisted of intracranial hemorrhage and other bleeding that led to decreases in hemoglobin greater than 5 g/dL.
Minor bleeding included spontaneous gross hematuria, spontaneous hematemesis, other observed blood loss with a hemoglobin decrease of more than 3 g/dL, and other hemoglobin decreases that were greater than 4 g/dL but less than 5 g/dL. In patients who received transfusions, the corresponding loss in hemoglobin was estimated through an adaptation of the method of Landefeld et al. Table 2: Bleeding and Transfusions in the PURSUIT and ESPRIT Studies The majority of major bleeding reactions in the ESPRIT study occurred at the vascular access site (1 and 8 patients, or 0.1% and 0.8% in the placebo and eptifibatide groups, respectively).
Bleeding at “other” locations occurred in 0.2% and 0.4% of patients, respectively. In the PURSUIT study, the greatest increase in major bleeding in eptifibatide-treated patients compared to placebo-treated patients was also associated with bleeding at the femoral artery access site (2.8% versus 1.3%). Oropharyngeal (primarily gingival), genitourinary, gastrointestinal, and retroperitoneal bleeding were also seen more commonly in eptifibatide-treated patients compared to placebo-treated patients.
Among patients experiencing a major bleed in the IMPACT II study, an increase in bleeding on eptifibatide versus placebo was observed only for the femoral artery access site (3.2% versus 2.8%). Table 3 displays the incidence of TIMI major bleeding according to the cardiac procedures carried out in the PURSUIT study. The most common bleeding complications were related to cardiac revascularization (CABG-related or femoral artery access site bleeding).
A corresponding table for ESPRIT is not presented, as every patient underwent PCI in the ESPRIT study and only 11 patients underwent CABG. Table 3: Major Bleeding by Procedures in the PURSUIT Study In the PURSUIT and ESPRIT studies, the risk of major bleeding with eptifibatide increased as patient weight decreased. This relationship was most apparent for patients weighing less than 70 kg.
Intracranial Hemorrhage and Stroke Intracranial hemorrhage was rare in the PURSUIT, IMPACT II, and ESPRIT clinical studies. In the ESPRIT study, there were 3 hemorrhagic strokes, 1 in the placebo group and 2 in the eptifibatide group. In addition there was 1 case of cerebral infarction in the eptifibatide group.
Immunogenicity/Thrombocytopenia The potential for development of antibodies to eptifibatide has been studied in 433 subjects. In both cases, plasma for antibody detection was collected approximately 30 days after each dose. The development of antibodies to eptifibatide at higher doses has not been evaluated.
In patients with suspected eptifibatide-related immune-mediated thrombocytopenia, IgG antibodies that react with the GP IIb/IIIa complex were identified in the presence of eptifibatide and in eptifibatide-naïve patients. These findings suggest acute thrombocytopenia after the administration of eptifibatide can develop as a result of naturally occurring drug-dependent antibodies or those induced by prior exposure to eptifibatide. Similar antibodies were identified with other GP IIb/IIIa ligand-mimetic agents.
Immune-mediated thrombocytopenia with eptifibatide may be associated with hypotension and/or other signs of hypersensitivity. In the PURSUIT and IMPACT II studies, the incidence of thrombocytopenia (<100,000/mm 3 or ≥50% reduction from baseline) and the incidence of platelet transfusions were similar between patients treated with eptifibatide and placebo. In the ESPRIT study, the incidence was 0.6% in the placebo group and 1.2% in the eptifibatide group.
Other Adverse Reactions In the PURSUIT and ESPRIT studies, the incidence of serious nonbleeding adverse reactions was similar in patients receiving placebo or eptifibatide (19% and 19%, respectively, in PURSUIT; 6% and 7%, respectively, in ESPRIT). In PURSUIT, the only serious nonbleeding adverse reaction that occurred at a rate of at least 1% and was more common with eptifibatide than placebo (7% versus 6%) was hypotension. Most of the serious nonbleeding adverse reactions consisted of cardiovascular reactions typical of a UA population.
In the IMPACT II study, serious nonbleeding adverse reactions that occurred in greater than 1% of patients were uncommon and similar in incidence between placebo- and eptifibatide-treated patients. Discontinuation of study drug due to adverse reactions other than bleeding was uncommon in the PURSUIT, IMPACT II, and ESPRIT studies, with no single reaction occurring in >0.5% of the study population (except for "other" in the ESPRIT study).
Postmarketing Experience
The following adverse reactions have been reported in post-approval use of eptifibatide in combination with heparin and aspirin. Because the reactions below are reported voluntarily from a population of uncertain size, it is generally not possible to reliably estimate their frequency or establish a causal relationship to drug exposure: cerebral, GI, and pulmonary hemorrhage. Fatal bleeding reactions have been reported.
Acute profound thrombocytopenia, as well as immune-mediated thrombocytopenia, have been reported.
| Note: Denominator is based on patients for whom data are available. For major and minor bleeding, patients are counted only once according to the most severe classification. Includes transfusions of whole blood, packed red blood cells, fresh frozen plasma, cryoprecipitate, platelets, and autotransfusion during the initial hospitalization. | ||
| PURSUIT (ACS) Placebo n (%) | Eptifibatide 180/2 n (%) | |
| Patients | 4696 | 4679 |
| Major bleeding | 425 (9.3%) | 498 (10.8%) |
| Minor bleeding | 347 (7.6%) | 604 (13.1%) |
| Requiring transfusions | 490 (10.4%) | 601 (12.8%) |
| ESPRIT (PCI) Placebo n (%) | Eptifibatide 180/2/180 n (%) | |
| Patients | 1024 | 1040 |
| Major bleeding | 4 (0.4%) | 13 (1.3%) |
| Minor bleeding | 18 (2%) | 29 (3%) |
| Requiring transfusions | 11 (1.1%) | 16 (1.5%) |
| Note: Denominators are based on the total number of patients whose TIMI classification was resolved. | ||
| Placebo n (%) | Eptifibatide 180/2 n (%) | |
| Patients | 4577 | 4604 |
| Overall incidence of major bleeding | 425 (9.3%) | 498 (10.8%) |
| Breakdown by procedure: | ||
| CABG | 375 (8.2%) | 377 (8.2%) |
| Angioplasty without CABG | 27 (0.6%) | 64 (1.4%) |
| Angiography without angioplasty or CABG | 11 (0.2%) | 29 (0.6%) |
| Medical therapy only | 12 (0.3%) | 28 (0.6%) |
Warnings & Cautions for Eptifibatide
Bleeding Bleeding is the most common complication encountered during eptifibatide therapy. Administration of eptifibatide is associated with an increase in major and minor bleeding, as classified by the criteria of the Thrombolysis in Myocardial Infarction Study group (TIMI). Most major bleeding associated with eptifibatide has been at the arterial access site for cardiac catheterization or from the gastrointestinal or genitourinary tract.
Minimize the use of arterial and venous punctures, intramuscular injections, and the use of urinary catheters, nasotracheal intubation, and nasogastric tubes. When obtaining intravenous access, avoid non-compressible sites (e.g., subclavian or jugular veins). Use of Thrombolytics, Anticoagulants, and Other Antiplatelet Agents Risk factors for bleeding include older age, a history of bleeding disorders, and concomitant use of drugs that increase the risk of bleeding (thrombolytics, oral anticoagulants, nonsteroidal anti-inflammatory drugs, and P2Y 12 inhibitors).
Concomitant treatment with other inhibitors of platelet receptor glycoprotein (GP) IIb/IIIa should be avoided. In patients treated with heparin, bleeding can be minimized by close monitoring of the aPTT and ACT. Care of the Femoral Artery Access Site in Patients Undergoing Percutaneous Coronary Intervention (PCI) In patients undergoing PCI, treatment with eptifibatide is associated with an increase in major and minor bleeding at the site of arterial sheath placement.
After PCI, eptifibatide infusion should be continued until hospital discharge or up to 18 to 24 hours, whichever comes first. Heparin use is discouraged after the PCI procedure. Early sheath removal is encouraged while eptifibatide is being infused.
In any case, both heparin and eptifibatide should be discontinued and sheath hemostasis should be achieved at least 2 to 4 hours before hospital discharge. If bleeding at access site cannot be controlled with pressure, infusion of eptifibatide and heparin should be discontinued immediately.
Thrombocytopenia There have been reports of acute, profound thrombocytopenia (immune-mediated and non-immune mediated) with eptifibatide. In the event of acute profound thrombocytopenia or a confirmed platelet decrease to <100,000/mm 3, discontinue eptifibatide and heparin (unfractionated or low-molecular weight). Monitor serial platelet counts, assess the presence of drug-dependent antibodies, and treat as appropriate.
There has been no clinical experience with eptifibatide initiated in patients with a baseline platelet count <100,000/mm 3. If a patient with low platelet counts is receiving eptifibatide, their platelet count should be monitored closely.
Drug Interactions with Eptifibatide
Use of Thrombolytics, Anticoagulants, and Other Antiplatelet Agents Coadministration of antiplatelet agents, thrombolytics, heparin, aspirin, and chronic NSAID use increases the risk of bleeding. Concomitant treatment with other inhibitors of platelet receptor GP IIb/IIIa should be avoided.
Pregnancy Safety for Eptifibatide
Pregnancy Risk Summary Available data on eptifibatide use in pregnant women from published literature and the pharmacovigilance database are insufficient to establish a drug-associated risk of major birth defects, miscarriage or adverse maternal or fetal outcomes. Untreated myocardial infarction can be fatal to the pregnant woman and fetus (see Clinical Considerations). In animal reproduction studies, there was no evidence of adverse developmental effects when eptifibatide was administered intravenously to pregnant rats and rabbits at approximately 4 times the recommended maximum daily human dose.
The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is respectively.
Therapy for the pregnant woman should not be withheld because of potential concerns regarding the effects of eptifibatide on the fetus Data Animal Data Embryo-fetal development studies have been performed by continuous intravenous infusion of eptifibatide in pregnant rats during the period of organogenesis at total daily doses of up to 72 mg/kg/day (about 4 times the recommended maximum daily human dose on a body surface area basis) and in pregnant rabbits during the period of organogenesis at total daily doses of up to 36 mg/kg/day (also about 4 times the recommended maximum daily human dose on a body surface area basis). These studies revealed no evidence of harm to the fetus due to eptifibatide.
Pediatric Use of Eptifibatide
Pediatric Use Safety and effectiveness of eptifibatide in pediatric patients have not been studied.
Contraindications for Eptifibatide
Treatment with eptifibatide injection is contraindicated in patients with: A history of bleeding diathesis, or evidence of active abnormal bleeding within the previous 30 days Severe hypertension (systolic blood pressure >200 mm Hg or diastolic blood pressure >110 mm Hg) not adequately controlled on antihypertensive therapy Major surgery within the preceding 6 weeks History of stroke within 30 days or any history of hemorrhagic stroke Current or planned administration of another parenteral GP IIb/IIIa inhibitor Dependency on renal dialysis Hypersensitivity to eptifibatide injection or any component of the product (hypersensitivity reactions that occurred included anaphylaxis and urticaria) Bleeding diathesis or bleeding within the previous 30 days Severe uncontrolled hypertension Major surgery within the preceding 6 weeks Stroke within 30 days or any history of hemorrhagic stroke Coadministration of another parenteral GP IIb/IIIa inhibitor Dependency on renal dialysis Known hypersensitivity to any component of the product
Overdosage Information for Eptifibatide
There has been only limited experience with overdosage of eptifibatide. There were 8 patients in the IMPACT II study, 9 patients in the PURSUIT study, and no patients in the ESPRIT study who received bolus doses and/or infusion doses more than double those called for in the protocols. None of these patients experienced an intracranial bleed or other major bleeding.
Eptifibatide was not lethal to rats, rabbits, or monkeys when administered by continuous intravenous infusion for 90 minutes at a total dose of 45 mg/kg (about 2 to 5 times the recommended maximum daily human dose on a body surface area basis). Symptoms of acute toxicity were loss of righting reflex, dyspnea, ptosis, and decreased muscle tone in rabbits and petechial hemorrhages in the femoral and abdominal areas of monkeys. From in vitro studies, eptifibatide is not extensively bound to plasma proteins and thus may be cleared from plasma by dialysis.
Clinical Studies of Eptifibatide
Non-ST-Segment Elevation Acute Coronary Syndrome
Non-ST-segment elevation acute coronary syndrome is defined as prolonged (≥10 minutes) symptoms of cardiac ischemia within the previous 24 hours associated with either ST-segment changes (elevations between 0.6 mm and 1 mm or depression >0.5 mm), T-wave inversion (>1 mm), or positive CK-MB. This definition includes "unstable angina" and "NSTEMI" but excludes MI that is associated with Q waves or greater degrees of ST-segment elevation. PURSUIT (Platelet Glycoprotein IIb/IIIa in Unstable Angina: Receptor Suppression Using Eptifibatide Therapy) PURSUIT was a 726-center, 27-country, double-blind, randomized, placebo-controlled study in 10,948 patients presenting with UA or NSTEMI.
Important exclusion criteria included a history of bleeding diathesis, evidence of abnormal bleeding within the previous 30 days, uncontrolled hypertension, major surgery within the previous 6 weeks, stroke within the previous 30 days, any history of hemorrhagic stroke, serum creatinine >2 mg/dL, dependency on renal dialysis, or platelet count <100,000/mm 3. The infusion was continued for 72 hours, until hospital discharge, or until the time of CABG, whichever occurred first, except that if PCI was performed, the eptifibatide infusion was continued for 24 hours after the procedure, allowing for a duration of infusion up to 96 hours. The lower-infusion-rate arm was stopped after the first interim analysis when the 2 active-treatment arms appeared to have the same incidence of bleeding.
This was a "real world" study; each patient was managed according to the usual standards of the investigational site; frequencies of angiography, PCI, and CABG therefore differed widely from site to site and from country to country. Of the patients in PURSUIT, 13% were managed with PCI during drug infusion, of whom 50% received intracoronary stents; 87% were managed medically (without PCI during drug infusion). The majority of patients received aspirin (75 to 325 mg once daily).
Heparin was administered intravenously or subcutaneously, at the physician's discretion, most commonly as an intravenous bolus of 5,000 units followed by a continuous infusion of 1,000 units/h. For patients weighing less than 70 kg, the recommended heparin bolus dose was 60 units/kg followed by a continuous infusion of 12 units/kg/h. A target aPTT of 50 to 70 seconds was recommended.
The primary endpoint of the study was the occurrence of death from any cause or new MI (evaluated by a blinded Clinical Endpoints Committee) within 30 days of randomization. The reduction in the incidence of endpoint events in patients receiving eptifibatide was evident early during treatment, and this reduction was maintained through at least 30 days (see Figure 1). Table 5 also shows the incidence of the components of the primary endpoint, death (whether or not preceded by an MI) and new MI in surviving patients at 30 days.
Table 5: Clinical Events in the PURSUIT Study or Myocardial Infarction Within 30 Days of Randomization in the PURSUIT Study Treatment with eptifibatide prior to determination of patient management strategy reduced clinical events regardless of whether patients ultimately underwent diagnostic catheterization, revascularization (i.e., PCI or CABG surgery) or continued to receive medical management alone. Table 6 shows the incidence of death or MI within 72 hours. Table 6: Clinical Events (Death or MI) in the PURSUIT Study Within 72 Hours of Randomization All of the effect of eptifibatide was established within 72 hours (during the period of drug infusion), regardless of management strategy.
Moreover, for patients undergoing early PCI, a reduction in events was evident prior to the procedure. This difference may be a true treatment difference, the effect of other differences in these subgroups, or a statistical anomaly. No differential outcomes were seen between male and female patients undergoing PCI (see results for ESPRIT).
Follow-up data were available through 165 days for 10,611 patients enrolled in the PURSUIT trial (96.9% of the initial enrollment). This follow-up included 4566 patients who received eptifibatide at the 180/2 dose. As reported by the investigators, the occurrence of death from any cause or new MI for patients followed for at least 165 days was reduced from 13.6% with placebo to 12.1% with eptifibatide 180/2.
Figure 1: Kaplan-Meier Plot of Time to Death or Myocardial Infarction Within 30 Days of Randomization in the PURSUIT Study
Percutaneous Coronary Intervention (PCI) IMPACT II (Eptifibatide to Minimize Platelet Aggregation and Prevent Coronary Thrombosis II) IMPACT II was a multicenter, double-blind, randomized, placebo-controlled study conducted in the United States in 4010 patients undergoing PCI. Major exclusion criteria included a history of bleeding diathesis, major surgery within 6 weeks of treatment, gastrointestinal bleeding within 30 days, any stroke or structural CNS abnormality, uncontrolled hypertension, PT >1.2 times control, hematocrit <30%, platelet count <100,000/mm3, and pregnancy. The patients were 92% Caucasian, 5% Black, and 3% Hispanic.
Forty-one percent of the patients underwent PCI for ongoing ACS. The primary endpoint was the composite of death, MI, or urgent revascularization, analyzed at 30 days after randomization in all patients who received at least 1 dose of study drug. As shown in Table 7, each eptifibatide regimen reduced the rate of death, MI, or urgent intervention, although at 30 days, this finding was statistically significant only in the lower-dose eptifibatide group.
As in the PURSUIT study, the effects of eptifibatide were seen early and persisted throughout the 30-day period. Table 7: Clinical Events in the IMPACT II Study ESPRIT (Enhanced Suppression of the Platelet IIb/IIIa Receptor with Eptifibatide Therapy) The ESPRIT study was a multicenter, double-blind, randomized, placebo-controlled study conducted in the United States and Canada that enrolled 2064 patients undergoing elective or urgent PCI with intended intracoronary stent placement. Patients received a wide variety of stents.
Eptifibatide infusion was continued for 18 to 24 hours after PCI or until hospital discharge, whichever came first. The primary endpoint of the ESPRIT study was the composite of death, MI, urgent target vessel revascularization (UTVR), and "bailout" to open-label eptifibatide due to a thrombotic complication of PCI (TBO) (e.g., visible thrombus, "no reflow," or abrupt closure) at 48 hours. MI, UTVR, and TBO were evaluated by a blinded Clinical Events Committee.
As shown in Table 8, the incidence of the primary endpoint and selected secondary endpoints was significantly reduced in patients who received eptifibatide. A treatment benefit in patients who received eptifibatide was seen by 48 hours and at the end of the 30-day observation period. Consistent with previous studies of GP IIb/IIIa inhibitors, most of the benefit achieved acutely with eptifibatide was in the reduction of MI.
There was no treatment difference with respect to sex in ESPRIT. Follow-up (12-month) mortality data were available for 2024 patients (1017 on eptifibatide) enrolled in the ESPRIT trial (98.1% of the initial enrollment). Twelve-month clinical event data were available for 1964 patients (988 on eptifibatide), representing 95.2% of the initial enrollment.
| Death or MI | Placebo (n = 4739) n (%) | Eptifibatide (180 mcg/kg bolus then 2 mcg/kg/min infusion) (n = 4722) n (%) | p-value |
|---|---|---|---|
| 3 days | 359 (7.6%) | 279 (5.9%) | 0.001 |
| 7 days | 552 (11.6%) | 477 (10.1%) | 0.016 |
| 30 days | |||
| Death or MI (primary endpoint) | 745 (15.7%) | 672 (14.2%) | 0.042 |
| Death | 177 (3.7%) | 165 (3.5%) | |
| Nonfatal MI | 568 (12%) | 507 (10.7%) |
| Placebo | Eptifibatide (180 mcg/kg bolus then 2 mcg/kg/min infusion) | |
|---|---|---|
| Overall patient population | n = 4739 | n = 4722 |
| – At 72 hours | 7.6% | 5.9% |
| Patients undergoing early PCI | n = 631 | n = 619 |
| – Pre-procedure (nonfatal MI only) | 5.5% | 1.8% |
| – At 72 hours | 14.4% | 9% |
| Patients not undergoing early PCI | n = 4108 | n = 4103 |
| – At 72 hours | 6.5% | 5.4% |
| *Kaplan-Meier estimate of event rate. | |||
| Placebo n (%) | Eptifibatide (135 mcg/kg bolus then 0.5 mcg/kg/min infusion) n (%) | Eptifibatide (135 mcg/kg bolus then 0.75 mcg/kg/min infusion) n (%) | |
| Patients | 1285 | 1300 | 1286 |
| Abrupt Closure | 65 (5.1%) | 36 (2.8%) | 43 (3.3%) |
| p-value versus placebo | 0.003 | 0.03 | |
| Death, MI, or Urgent Intervention | |||
| 24 hours | 123 (9.6%) | 86 (6.6%) | 89 (6.9%) |
| p-value versus placebo | 0.006 | 0.014 | |
| 48 hours | 131 (10.2%) | 99 (7.6%) | 102 (7.9%) |
| p-value versus placebo | 0.021 | 0.045 | |
| 30 days (primary endpoint) | 149 (11.6%) | 118 (9.1%) | 128 (10%) |
| p-value versus placebo | 0.035 | 0.179 | |
| Death or MI | |||
| 30 days | 110 (8.6%) | 89 (6.8%) | 95 (7.4%) |
| p-value versus placebo | 0.102 | 0.272 | |
| 6 months | 151 (11.9%) | 136 (10.6%) | 130 (10.3%) |
| p-value versus placebo | 0.297 | 0.182 | |
| Eptifibatide was administered as 180 mcg/kg boluses at times 0 and 10 minutes and an infusion at 2 mcg/kg/min. | ||||
| Placebo (n = 1024) | Eptifibatide* (n = 1040) | Relative Risk (95% CI) | p-value | |
| Death, MI, UTVR, or Thrombotic “Bailout” | ||||
| 48 hours (primary endpoint) | 108 (10.5%) | 69 (6.6%) | 0.629 (0.471, 0.84) | 0.0015 |
| 30 days | 120 (11.7%) | 78 (7.5%) | 0.64 (0.488, 0.84) | 0.0011 |
| Death, MI, or UTVR | ||||
| 48 hours | 95 (9.3%) | 62 (6%) | 0.643 (0.472, 0.875) | 0.0045 |
| 30 days (key secondary endpoint) | 107 (10.4%) | 71 (6.8%) | 0.653 (0.49, 0.871) | 0.0034 |
| Death or MI | ||||
| 48 hours | 94 (9.2%) | 57 (5.5%) | 0.597 (0.435, 0.82) | 0.0013 |
| 30 days | 104 (10.2%) | 66 (6.3%) | 0.625 (0.465, 0.84) | 0.0016 |
| Percentages are Kaplan-Meier event rates. | |||
| Placebo (n = 1024) | Eptifibatide (n = 1040) | Hazard Ratio (95% CI) | |
| Death, MI, or Target Vessel Revascularization | |||
| 6 months | 187 (18.5%) | 146 (14.3%) | 0.744 (0.599, 0.924) |
| 1 year | 222 (22.1%) | 178 (17.5%) | 0.762 (0.626, 0.929) |
| Death, MI | |||
| 6 months | 117 (11.5%) | 77 (7.4%) | 0.631 (0.473, 0.841) |
| 1 year | 126 (12.4%) | 83 (8%) | 0.63 (0.478, 0.832) |
Drug information sourced from the FDA. This content is for informational purposes only and does not constitute medical advice. Consult a healthcare professional before making any medication decisions.
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