Eptifibatide is Noninferior to Abciximab in Primary PCI

Eptifibatide is Noninferior to Abciximab in Primary PCI – Results From the SCAAR (Swedish Coronary Angiography and Angioplasty Registry) Axel Åkerblom, MD 1, 2, Stefan K. James, MD, Ph. D 1, 2, Michail Koutouzis, MD, Ph. D 3 Bo Lagerqvist, MD, Ph. D 1, 2, Ulf Stenestrand, MD, Ph. D 1, 4, Bodil Svennblad, Ph. D 1, Jonas Oldgren MD, Ph. D 1, 2. Uppsala Clinical Research Center 1, University Hospitals in Uppsala 2, Gothenburg 3, and Linkoping 4, Sweden J Am Coll Cardiol 2010; 56: 470– 5

Disclosures • AÅ has nothing to disclose • SJ has received research support to institution from Eli Lilly, and has research cooperation with Eli Lilly (abciximab) and Schering. Plough (eptifibatide). • MK has nothing to disclose • BL has nothing to disclose • US has nothing to disclose. Deceased in February 2010 • BS has nothing to disclose • JO has nothing to disclose

Background • Glycoprotein IIb/IIIa inhibitors (GPI) potently inhibit platelet aggregation. • GPI reduce ischemic events in patients undergoing PCI, especially in patients with acute coronary syndromes (ACS) [1 -4]. • Eptifibatide receives a lower level of recommendation in guidelines regarding STEMI patients due to less scientific validation compared to abciximab [5, 6]. • No head to head comparisons between eptifibatide and abciximab has been presented.

Methods • 2004, two large Swedish University Hospitals changed their GP IIb/IIIa inhibitor therapy from abciximab to eptifibatide on all indications to reduce pharmacological costs. • Some additional hospitals used both drugs. • The remainder of hospitals continued with abciximab on all indications. • The patient population was derived from SCAAR (Swedish Coronary Angiography and Angioplasty Registry) – a register where all angiographies and angioplasties in Sweden are entered [7]. • The SCAAR database was merged with the Swedish Cause of Death Register and the Swedish National Patient Register to obtain long term follow up.

Methods • The primary hypothesis was that eptifibatide would be noninferior to abciximab with respect to the primary end point of death or MI at 1 year. • The pre-specified non-inferiority margin was set to 1. 29, preserving 50% of the estimated effect by abciximab by the point estimate of the odds ratio (OR) of abciximab versus placebo in patients with STEMI [8, 9]. • Logistic regression with drug as a predictor was used. To compensate for pre-treatment differences, propensity score was added as a predictor in a multivariable logistic regression [10].

Results - Background Characteristics Clinical Characteristics • Age Female Gender Diabetes Hypertension Hyperlipidemia Congestive Heart Failure Current Smoker Previous Myocardial Infarction -"PCI -"CABG -"Stroke -"Renal Failure -"Major Bleeding n=11479 11479 11478 11479 11476 11479 11465 11479 Abciximab n=9124 65 (57 - 74) 28. 1% (2568) 17. 7% (1616) 34. 6% (3157) 18. 1% (1647) 3. 3% ( 300) 29. 5% (2688) 14. 9% (1355) 8. 6% ( 782) 2. 7% ( 242) 5. 0% ( 458) 1. 0% ( 88) 3. 2% ( 291) Eptifibatide n=2355 65 (57 - 74) 27. 0% (636) 16. 3% (385) 33. 6% (791) 16. 5% (389) 2. 9% ( 69) 27. 7% ( 652) 14. 8% ( 349) 9. 0% ( 211) 3. 0% ( 71) 4. 1% ( 97) 1. 2% ( 28) 2. 6% ( 62) Age represents median and within parenthesis the 25 th and 75 th percentile

Results - Background Characteristics Interventional Characteristics n=11479 Radial Artery Puncture 11473 Ongoing or Periprocedural Treatment: Acetylsalisylic Acid 11459 Clopidogrel 11438 Unfractionated Heparin 11466 Low Molecular Weight Heparin 11465 Warfarin 11349 Bare metal stent 11477 Drug eluting stent 11477 Number of Stents Implanted 0 11479 1 2 3 4 5 6 7 Coronary Pathology Inconclusive 11479 Atheromatosis / No Significant Stenosis 1 Vessel Disease not Left Main 2 -“ 3 -“Left Main Stenosis Procedure Year 2004 11479 2005 2006 2007 Abciximab Eptifibatide n=9124 n=2355 11. 0% (1000) 29. 0% (682) 94. 7% (8622) 84. 7% (7718) 69. 7% (6356) 32. 0% (2913) 1. 2% (110) 67. 6% (6165) 25. 4% (2320) 7. 0% (639) 63. 8% (5825) 21. 7% (1982) 5. 6% (512) 1. 4% (129) 0. 4% (32) 0. 0% (3) 0. 0% (2) 96. 9% (2277) 93. 6% (2179) 92. 8% (2179) 11. 2% (263) 0. 4% (10) 85. 3% (2009) 9. 1% (215) 5. 6% (131) 54. 0% (1271) 27. 3% (642) 9. 0% (213) 3. 0% (70) 0. 8% (20) 0. 1% (3) 0. 2% (5) 1. 3% (117) 0. 4% (34) 49. 3% (4499) 27. 1% (2473) 17. 5% (1599) 4. 4% (402) 20. 9% (1909) 23. 2% (2119) 27. 8% (2537) 28. 0% (2559) 0. 2% (5) 0. 3% (6) 44. 5% (1047) 30. 4% (717) 20. 0% (472) 4. 6% (108) 9. 5% (224) 30. 1% (709) 29. 4% (693) 31. 0% (729)

Results A total of 11, 479 patients with STEMI underwent Primary PCI with adjunctive GPI therapy between 2004 and 2007. The unadjusted OR for eptifibatide versus abciximab was 0. 95 (95% CI: 0. 84 to 1. 08) (Fig. 1). Multivariate adjustment (n=11, 317) with propensity score also showed non-inferiority for eptifibatide versus abciximab. OR of 0. 94 (95% CI: 0. 82 to 1. 09) (Fig. 2).

Results – non adjusted primary outcome (Death or MI) • Figure 1: Cumulative non-adjusted event rates of the primary combined endpoint of death or myocardial infarction during one year of follow up for patients that underwent primary PCI with either eptifibatide (dashed line) or abciximab (solid line). The unadjusted odds ratio (OR) and 95 % confidence interval for eptifibatide versus abciximab was 0. 95 [0. 84 – 1. 08]

Results – adjusted primary outcome (Death or MI) • Figure 2: Cumulative event rates, estimated at the mean propensity score, of death or myocardial infarction during one year of follow up for patients that underwent primary PCI and either received eptifibatide (dashed line) or abciximab (solid line). The odds ratio of 0. 94 [95 % CI 0. 82 – 1. 09] suggested non-inferiority of eptifibatide as the prespecified non-inferiority margin of 1. 29 for the primary endpoint was met.

Results – secondary outcome, Death. • Figure 3: Cumulative event rates of the secondary endpoint of death alone, estimated at the mean propensity score, during one year of follow up for patients that underwent primary PCI with adjunctive eptifibatide (dashed line) or abciximab (solid line). The adjusted secondary endpoints of death showed non-inferiority, OR 0. 99 [95 % CI 0. 82 – 1. 19].

Results – secondary outcome, MI. • Figure 4: Cumulative event rates of the secondary endpoint of myocardial infarction alone, estimated at the mean propensity score, during one year of follow up for patients that underwent primary PCI and received either eptifibatide (dashed line) or abciximab (solid line). The adjusted secondary endpoints of myocardial infarction alone also showed non-inferiority OR 0. 88 [95 % CI 0. 73 – 1. 05].

Limitations • This is a nonrandomized register study where unknown confounders may have affected the results although appropriate statistical adjustments including the use of propensity score have been used. • During the study period the initiation of other anticoagulants and treatments may have changed clinical practice. • More potent P 2 Y 12 inhibitors (e. g prasugrel or ticagrelor) have not been evaluated in this study. Their possible future use may limit the benefit of GP IIb/IIIa inhibitors in clinical practice.

Conclusion • This large registry study suggests that eptifibatide is noninferior to abciximab in patients with STEMI undergoing primary PCI with respect to death or MI during one year, thereby supporting the use of either drug in clinical practice.

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