Use of platelet glycoprotein IIb / IIIa inhibitors in primary percutaneous coronary intervention : 10-year experience in Brazil

Background: Individualized use of glycoprotein IIb/IIIa inhibitors during primary percutaneous coronary intervention in scenarios with high thrombotic load or occurrence of coronary flow abnormalities may be considered, despite scarce scientific evidence. Our objective was to compare patients undergoing primary percutaneous coronary intervention treated or not with glycoprotein IIb/IIIa inhibitors during the procedure. Methods: A national, multicenter, retrospective study that included consecutive patients undergoing primary percutaneous coronary intervention, treated or not with glycoprotein IIb/IIIa inhibitors, between June 2006 and March 2016, using the database of the Central Nacional de Intervenções Cardiovasculares (CENIC). Results: We enrolled 18,690 patients, of which 3,032 (16.2%) received glycoprotein IIb/IIIa inhibitors. The mean age was 61.5±12.4 years, 69.5% were men, and 19.9% had diabetes mellitus. The group receiving glycoprotein IIb/IIIa inhibitors had a higher prevalence of long, thrombotic, bifurcation lesions, occlusions or TIMI flow grade <2. This group showed higher mortality (3.7% vs. 4.8%; p=0.0046), reinfarction (0.5% vs. 1.1%; p<0.0001) and major adverse cardiac event rates (4.0% vs. 5.7%; p<0.0001). In the univariate analysis, the use of glycoprotein IIb/IIIa inhibitors was associated with a higher chance of death (RR 1.31; 95%CI 1.09-1.58; p=0.0048), but was not confirmed as an independent predictor in the multivariate analysis. Conclusion: Among patients undergoing primary percutaneous coronary intervention, the group treated with glycoprotein IIb/IIIa inhibitors had greater clinical severity and anatomical complexity, and worse in-hospital clinical outcomes.


INtrodUctIoN
Adjunctive platelet glycoprotein (GP) IIb/IIIa inhibitors in acute coronary syndrome (ACS) aims to reduce thrombus load and restore coronary perfusion.6][7][8] In Brazil, only tirofiban and abciximab are commercially available. 9n combination with current antithrombotic therapies, routine use of GP IIb/IIIa inhibitors is not beneficial, and can lead to higher rates of severe bleeding. 10Individualized use may be considered in specific situations, such as high thrombotic load, slow/no reflow phenomenon, coronary dissections, or other thrombotic complications. 11,12his study aimed to compare the profile and in-hospital outcomes of patients subjected to primary PCI, trea ted or not with adjunctive GP IIb/IIIa inhibitors, in addition to verifying the influence of variables of interest on mortality.

MetHods
A national, multicenter, retrospective study of all consecutive patients subjected to primary PCI, between June 2006 and March 2016, comparing patients treated or not with GP IIb/IIIa inhibitors during the pro cedure.Data were collected from the database of the Central Nacional de Intervenções Cardiovasculares (CENIC; http://www.corehemo.net/).
Patients were characterized by clinical, angiographic, procedure-related and MACE criteria during the hospital phase, including the occurrence of death, non-fatal infarction or urgent coronary artery bypass surgery (CABG).This study follows the recommendations of the Declaration of Helsinki and Resolution 466/12 of the National Health Council and has been approved by the local ethics committee under protocol 2.992.506(CAAE: 01989218.2.0000.5485).

statistical analysis
Descriptive statistics were presented for clinical, angiographic and procedure-related characteristics, in-hospital clinical outcomes, and procedural success in patients eligible for the analysis.For continuous variables, mean and standard deviation was presented and, for categorical variables, contingency tables were presented with absolute and percentage frequencies.
Comparative analysis of categorical variables was performed using the Chi-square test and, when necessary, the likelihood ratio.Continuous variables were compared using the Student's t test.For multiple comparisons, we used the Bonferroni correction.
To assess the influence of variables of interest on mortality, the simple logistic regression model was used.The independent variables in the univariate regression model were tested with the forward selection method and included in the multivariate analysis.Variables with high loss of information (e.g.ventricular dysfunction and collateral circulation) were disregarded in the multiple analysis.For all analyses, the level of significance was set as p<0.05.
Regarding in-hospital clinical outcomes, mortality was higher (4.8% vs. 3.7%; p=0.0046) in the group treated with GP IIb/IIIa inhibitors, as well as the incidence of MACE (5.7% vs. 4.0%; p<0.0001) and reinfarction (1.1% vs. 0.5%; p<0.0001) (Table 4).In the univariate analysis,    the use of GP IIb/IIIa inhibitors was associated with a greater chance of death (RR 1.31; 95%CI: 1.09-1.58;p=0.0048), but it was not confirmed as an independent predictor in the multivariate analysis.In the latter, the variables that best correlated with mortality were age, female gender, hypertension, dyslipidemia, diabetes mellitus, prior infarction, Killip class, and extent of the coronary artery disease (Table 5).

dIscUssIoN
This study analyzed 18,690 patients subjected to primary PCI, of which 3,032 (16.2%) received GP IIb/IIIa inhibitors as adjunct therapy, amounting to a sizeable national case series.This group had greater clinical severity and anatomical complexity, and worse in-hospital outcomes.
Routine use of GP IIb/IIIa inhibitors did not show any benefits as an add-on therapy to PCI. 10,12 However, in non-ST-segment elevation ACS, a meta-analysis demonstrated a discrete reduction in 30-day mortality and acute myocardial infarction rates in patients categorized as high risk (positive for myocardial necrosis mar kers, high thrombus load or complex lesions). 11In addition, a meta-regression analysis showed that the use of GP IIb/IIIa inhibitors led to an isolated reduction of 30-day mortality rates in patients aged over 65 years, hemodynamically unstable, with diabetes mellitus or prior acute myocardial infarction. 12hen compared to intracoronary and intravenous administration of GP IIb/IIIa inhibitors, the meta-analysis showed a significant reduction in 30-day mortality and target-vessel revascularization rates, at the expense of higher rates of severe bleeding, favoring the former; 13 however, this finding was not further confirmed by randomized clinical trials. 14The meta-analysis by Elbadawi et al., in turn, showed a higher rate of final TIMI flow grade 3, myocardial blush grade II or III, and resolution of the ST-segment elevation, favoring the intracoronary administration without, however, any decrease in mortality, reinfarction or severe bleeding rates when compared with intravenous infusion. 15In our study, we were not able to perform any similar investigation due to missing information on the electronic data collection form.
In the more recent era of dual antiplatelet therapy with acetylsalicylic acid and P 2 Y12 receptor blockers, as well as the relatively frequent concomitant use of oral anticoagulants, the incidence of hemorrhagic complications in acute scenarios is not negligible.Therefore, when considering the use of GP IIb/IIIa inhibitors, one must pay attention to the increased incidence of bleeding and its prognostic impact on morbidity and mortality. 9Following an ACS, the efficacy, rapid onset of action, reversibility, influence of renal function, genetic variability and cost must be factored in when trying to predict the benefits of administering GP IIb/IIIa inhibitors, considering the risk of ischemia vs. hemorrhage on an individual basis. 16he limitations of this study were its retrospective nature, incomplete information on data collection forms, the non-adjudication of events, and a follow-up restricted to the hospital phase.The CENIC database is voluntarily fed by members of the Sociedade Brasileira de Hemodinâmica e Cardiologia Intervencionista (SBHCI) and subject to subnotifications and, therefore, may not be representative of the national reality, but rather a reflection of the practice in centers that regularly contribute to the system.coNcLUsIoN Among patients with acute myocardial infarction subjected to primary percutaneous coronary intervention, the group treated with glycoprotein IIb/IIIa inhibitors had greater clinical severity, anatomical complexity, and worse in-hospital outcomes.

Table 3 .
Procedure characteristics Results expressed as mean ± standard deviation and n (%).TIMI: Thrombolysis in Myocardium Infarction.

Table 4 .
In-hospital clinical outcomes