The role of Glycoprotein IIb/IIIa inhibitors in acute coronary syndromes and the interference with anemia.

The role played by glycoprotein (GP) IIb/IIIa inhibitors (GPI) has continuously evolved until the most recent Guidelines whereby they were stepped down from class I to class II recommendation for treating acute coronary syndromes (ACS). GPI compete with a wider use of ADP inhibitors and novel anticoagulant drugs although GPI use has greatly narrowed. However, GPI may still have a role. Several criteria were proposed to define post-PCI anemia which is strictly related to bleeding and transfusion. In ACS, it should be important to define anemia in comparative terms versus baseline levels: ≥ 15% of red blood cell decrease should be a practical cut-off value. If one wishes to concentrate on hemoglobin (Hb), a≥2g/dl Hb decrease from baseline should be considered. It is important to recognize post-PCI anemia in the setting of ACS. There are sub-populations exposed to short-term hemorrhagic and/or long-term ischemic risks. Ischemic and hemorrhagic risks need to be carefully evaluated along with thrombocytopenia and its prognostic significance in order to put all these blood and rheological parameters into a clinically oriented perspective on which therapeutical decisions should be based. Definition of high risk procedures (complexity, angiographic characteristics and patient's risk profile, regardless whether STEMI or NSTEMI) may help selecting GPI. There are positive elements in GPI use: efficacy, rapid onset and reversibility of action, absence of pharmacogenomic variability, pharmacoeconomic considerations and the possibility of intracoronary administration. All these elements should be evaluated when selecting these agents for therapeutics.

Reprint of "Decline in platelet count and long-term post-PCI ischemic events: implication of the intra-aortic balloon pump".

AIMS: Thrombocytopenia (TC) following a percutaneous coronary intervention (PCI) has been associated not only with hemorrhagic, but also with ischemic outcomes. The purpose of this study was to re-examine the relationship of TC with ischemic events at a 1-year follow-up, and investigate the possible associations. METHODS AND RESULTS: We studied a real-world, unselected population of ischemic patients undergoing PCI, totaling 861 patients-year, and divided into two groups: with TC (delta platelet count ≥25% from baseline to post-PCI during the hospital admission) and without TC. Compared with patients without TC, patients with TC had a higher and earlier incidence of both hemorrhagic and ischemic events. In them, the use of intra-aortic balloon pump (IABP) was ten-fold higher. In Kaplan-Meier curves assessing the contribution of both TC and IABP to outcome, IABP was a univariate detrimental factor additive to the role of TC. In a forced Cox model, the relative decline (delta) in platelet count (p=0.05) and the use of IABP (p=0.0001) were both associated with ischemic outcomes. After excluding all patients with IABP, the delta platelet count was no longer significantly associated with ischemic outcomes (p=0.66). After excluding all patients with shock and all those who undergone thrombolysis, there was still a relationship (p=0.0042) between the delta platelet count and ischemic events. CONCLUSIONS: In this patient population the use of IABP, but not thrombocytopenia per se, is a possible primary cause of worse ischemic outcomes.

Decline in platelet count and long-term post-PCI ischemic events: implication of the intra-aortic balloon pump.

AIMS: Thrombocytopenia (TC) following a percutaneous coronary intervention (PCI) has been associated not only with hemorrhagic, but also with ischemic outcomes. The purpose of this study was to re-examine the relationship of TC with ischemic events at a 1-year follow-up, and investigate the possible associations. METHODS AND RESULTS: We studied a real-world, unselected population of ischemic patients undergoing PCI, totaling 861 patients-year, and divided into two groups: with TC (delta platelet count ≥25% from baseline to post-PCI during the hospital admission) and without TC. Compared with patients without TC, patients with TC had a higher and earlier incidence of both hemorrhagic and ischemic events. In them, the use of intra-aortic balloon pump (IABP) was ten-fold higher. In Kaplan-Meier curves assessing the contribution of both TC and IABP to outcome, IABP was a univariate detrimental factor additive to the role of TC. In a forced Cox model, the relative decline (delta) in platelet count (p=0.05) and the use of IABP (p=0.0001) were both associated with ischemic outcomes. After excluding all patients with IABP, the delta platelet count was no longer significantly associated with ischemic outcomes (p=0.66). After excluding all patients with shock and all those who undergone thrombolysis, there was still a relationship (p=0.0042) between the delta platelet count and ischemic events. CONCLUSIONS: In this patient population the use of IABP, but not thrombocytopenia per se, is a possible primary cause of worse ischemic outcomes.

Is There Still a Role for Glycoprotein IIb/IIIa Antagonists in Acute Coronary Syndromes?

The role played by glycoprotein (GP) IIb/IIIa inhibitors has continuously evolved from the initial introduction in mid 90 s until the most recent guidelines for treating acute coronary syndromes, and competed with a wider use of ADP inhibitors and novel anticoagulant drugs, to the extent that they stepped down from class I to class II recommendation in the routine setting of acute coronary syndromes. As a consequence, GP IIb/IIIa use was greatly narrowed. The purpose of this review is to define the roles that GP IIb/IIIa inhibitors may still have in acute ischemic settings by explaining why in high risk patients they might be preferable and/or whether they might be added to ADP inhibitors also emphasizing the underlying mechanistic actions. It is concluded that there might be a more extensive use of GP IIb/IIIa inhibitors in patients presenting with acute coronary syndromes, strictly based on the definition for a high risk procedure: complexity, angiographic characteristics and patient's risk profile, regardless whether STEMI or NSTEMI. The positive elements one should appreciate in GP IIb/IIIa inhibitors are: efficacy, rapid onset and reversibility of action, absence of pharmacogenomic variability, pharmacoeconomic considerations and the possibility of intracoronary administration.

Long-term efficacy of high-dose tirofiban versus double-bolus eptifibatide in patients undergoing percutaneous coronary intervention.

BACKGROUND: There is no head-to-head comparison between tirofiban versus eptifibatide in patients undergoing percutaneous coronary intervention (PCI) when added to standard antiaggregating drugs (AAD) to prevent ischemic events within 1 year. METHODS: We compared real-world patients undergoing PCI who were on oral single AAD and were block randomized to receive, immediately preintervention, high-dose tirofiban (n = 519) or double-bolus eptifibatide (n = 147) and a second oral antiplatelet agent. The incidence of composite ischemic events within 1 year, including death, acute myocardial infarction, angina, stent thrombosis or repeat PCI or coronary bypass surgery (primary end-point) was modelled by forced Cox's regression. RESULTS: There were overall 65 composite ischemic events: 47 (9.1%) in the tirofiban group and 18 (12.2%) in the eptifibatide group (univariate log-rank test: P = 0.22). On the basis of 21 potential covariates fitted simultaneously, multivariable adjusted hazard ratios showed that age [hazard ratio 1.03, 95% confidence interval (CI) 1.01-1.07, P = 0.01], chronic renal failure (hazard ratio 3.21, 95% CI 1.02-10.10, P = 0.05), pre-PCI values of creatine kinase-myocardial band (CK-MB) (hazard ratio 1.002, 95% CI 1.0002-1.0054, P = 0.04), intra-aortic balloon pump (hazard ratio 5.88, 95% CI 12.33-14.85, P = 0.0002) and the presence of eptifibatide (hazard ratio 1.85, 95% CI 1.04-3.29, P = 0.04) were significant risk factors whereas thrombolysis by tenecteplase (hazard ratio 0.19, 95% CI 0.05-0.69, P = 0.01) was a significant protector. Interestingly, eptifibatide versus tirofiban efficacy was explained based on pre-PCI values of CK-MB. CONCLUSION: Head-to-head comparison between eptifibatide and tirofiban in patients undergoing PCI while on double AAD showed that eptifibatide had a lower efficacy on the incidence of composite ischemic events within 1 year, which might be explained by a reduced action on CK-MB pre-PCI.

GPIIb/IIIa Receptor Antagonism Using Small Molecules Provides no Additive Long-Term Protection after Percutaneous Coronary Intervention as Compared to Clopidogrel Plus Aspirin.

BACKGROUND: There is some controversy as to whether tirofiban or eptifibatide, two small anti-aggregating drugs (AAD), may reduce the incidence of composite ischemic events within one year in patients undergoing percutaneous coronary intervention (PCI) in the real clinical world. METHODS: We compared consecutive patients on oral double AAD (with clopidogrel and aspirin) who underwent PCI (n=207) and patients who were on single AAD and received a second AAD, just prior to PCI, and either high-dose tirofiban or double-bolus eptifibatide (double AAD plus small molecules group, n=666). The primary end point (incidence of composite ischemic events within one year) included death, acute myocardial infarction, unstable angina, stent thrombosis or repeat PCI or coronary bypass surgery (related to the target vessel PCI failure) and was modelled by Cox's regression. RESULTS: There were 89 composite ischemic events: 24 (11.6%) in double AAD alone and 65 (9.8%) in double AAD plus small molecules groups (log-rank test: p=0.36). Incidences by type of ischemic events were similar between the 2 groups. Based on 21 potential covariates fitted simultaneously, adjusted hazard ratios (HR and 95% confidence intervals) showed that age (HR 1.03, 1.01-1.06, p=0.01), diabetes (HR 1.68, 1.01-2.79, p=0.05) and intra aortic balloon pump (HR 5.12, 2.36-11.10, p=0.0001) were significant risk factors whereas thrombolysis by tenecteplase (HR 0.35, 0.13-0.98, p=0.05) and having had hypertension or anti-hypertensive treatment (HR 0.58, 0.36-0.93, p=0.03) were significant protectors for events. Whether small molecules were present provided a non significant additional benefit as compared to double AAD alone (HR 0.83, 0.51-1.36, p=0.46). Pre-PCI CK-MB were not useful to predict events (HR 1.01, 0.99-1.01, p=0.17). CONCLUSIONS: In clinical world patients undergoing PCI (rescue plus primary <13%) while on double AAD, based on clopidogrel plus aspirin, small molecules (tirofiban or eptifibatide) provided no additive long-term protection against the occurrence of composite ischemic events whereas thrombolysis by tenecteplase did.

Safety of downstream high-dose tirofiban bolus among 1578 patients undergoing percutaneous coronary intervention: the Sant'ANna TIrofiban Safety study.

BACKGROUND: The Sant'ANna TIrofiban Safety study (SANTISS) is an open-label investigator-initiated single-centre registry launched to assess the combination of bleeding and access site in-hospital complications (primary end-point) in patients undergoing percutaneous coronary intervention (PCI) by femoral approach only. METHODS: We compared patients who were on oral single antiaggregating drug (AAD) and received, just prior to PCI, high-dose tirofiban and a second oral antiplatelet agent (triple AAD: group 1, n = 970) with those who were already on an oral double AAD regimen and did not receive tirofiban (double AAD: group 2, n = 608). RESULTS: Group 2 patients were slightly older, presented less frequently with unstable angina and had chronic renal failure more frequently. They were more than twice as frequently on rescue PCI, being more than three-fold less frequently on primary PCI (all: 0.01>P < 0.001). Overall, there were 87 in-hospital (average 4.7 days of stay) complications: 51 (5.3%) in group 1 and 36 (5.9%) in group 2 (not significant). Haemotransfusions were needed in 34 patients: 21 (2.2%) in group 1 and 13 (2.1%) in group 2 (not significant). Of the 16 hospital deaths, eight (0.8%) were seen in group 1 and eight (1.3%) in group 2 (not significant). Multivariate prediction showed a high predictive accuracy (areas under the curve >0.700) of female sex, rescue PCI and chronic renal failure to index complications, with highly significant odds ratios. The presence of high-dose tirofiban did not increase complication risk. CONCLUSION: In the real world, high-dose tirofiban is well tolerated by patients on elective, primary or rescue PCI, and the in-hospital complication rate, including major bleeding, is low. This may have pharmacoeconomic consequences.