Abstract
Objective
We aimed to carry out a “real world” comparison of bivalirudin plus unfractionated heparin (UFH) versus abciximab plus UFH in patients undergoing primary percutaneous coronary intervention (PPCI) for ST elevation myocardial infarction (STEMI).
Methods
We included patients who had abciximab or bivalirudin during their PPCI in our unit between Sept 2009 and Nov 2011.
Results
The study included 516 and 484 patients in the bivalirudin and abciximab group respectively. There were more women in the bivalirudin group (29% vs 20%, p 0.001), while cardiogenic shock (6.4% vs 10.1%, p 0.04) and thrombectomy device use (76.6% vs 82%, p 0.04) were lower in the bivalirudin group.
The primary composite end point of 30-day mortality, 30-day definite stent thrombosis or non-CABG major bleeding was similar between the bivalirudin and abciximab groups (7.8% vs 9.5%, OR 0.8, 95% CI 0.5 to 1.2, p 0.4). There was also no difference in in-hospital mortality (4.1% vs 4.3%, p 0.9), 30-day mortality (5.2% vs 6.4%, p 0.5), 1-year mortality (9.1% vs 9.9%, p 0.7), 30-day stent thrombosis (1% vs 0.4%, p 0.5) and non-CABG bleeding (2.7 vs 3.7%, p 0.4) between the bivalirudin and abciximab group respectively. On Cox proportional hazard analysis after adjusting for all the co-variates, the use of bivalirudin was not a predictor of 30-day mortality (HR 1.13, 95% CI 0.7–1.9, p 0.7).
Conclusion
In this “real-world” observational study, there was no significant difference in the clinical outcome of PPCI for patients who had abciximab or bivalirudin after initial pre-treatment with UFH.
Summary for annotated table of contents
This study included 516 and 484 patients in the bivalirudin and abciximab group undergoing PPCI for STEMI. The primary composite end point of 30-day mortality, 30-day definite stent thrombosis or non-CABG major bleeding was similar between the bivalirudin and abciximab groups. In this “real-world” observational study, there was no significant difference in the clinical outcome of PPCI for patients who had abciximab or bivalirudin after initial pre-treatment with UFH.
1
Introduction
Primary percutaneous coronary intervention (PPCI) has been established as a standard therapy for ST elevation myocardial infarction (STEMI). In addition to thrombectomy and unfractionated heparin (UFH), thrombus burden in STEMI may require the use of more potent antithrombotic agents. The latest ESC guidelines for myocardial revascularization have class IIa recommendation for using abciximab and class I recommendation for using bivalirudin in STEMI . In the HORIZONS AMI trial, bivalirudin was shown to have a similar major adverse cardiovascular event (MACE) rate when compared to UFH plus glycoprotein IIb/IIIa inhibitor (GPI), but with reduced bleeding risk at 30 days . On further analysis of the same study, patients who had UFH prior to having bivalirudin (switch group) also had similar MACE outcomes to the GPI group (control group), but with significantly lower cardiac mortality at 30 days and also at 2 years . There was significantly lower major bleeding in the switch group suggesting that adding UFH to bivalirudin did not increase the risk of bleeding. Pre-randomization heparin has been shown as an independent predictor of reducing acute stent thrombosis in both arms of this study . As with most other large randomised trials, important patient subgroups are often excluded. In addition, the use of certain procedural techniques, adjunctive medications and devices often differs between randomised trials and the “real world” experience. Therefore, we aimed to carry out an observational study of primary PCI patients in our centre, to confirm that bivalirudin is truly non-inferior to abciximab in an unselected group of patients.
1
Introduction
Primary percutaneous coronary intervention (PPCI) has been established as a standard therapy for ST elevation myocardial infarction (STEMI). In addition to thrombectomy and unfractionated heparin (UFH), thrombus burden in STEMI may require the use of more potent antithrombotic agents. The latest ESC guidelines for myocardial revascularization have class IIa recommendation for using abciximab and class I recommendation for using bivalirudin in STEMI . In the HORIZONS AMI trial, bivalirudin was shown to have a similar major adverse cardiovascular event (MACE) rate when compared to UFH plus glycoprotein IIb/IIIa inhibitor (GPI), but with reduced bleeding risk at 30 days . On further analysis of the same study, patients who had UFH prior to having bivalirudin (switch group) also had similar MACE outcomes to the GPI group (control group), but with significantly lower cardiac mortality at 30 days and also at 2 years . There was significantly lower major bleeding in the switch group suggesting that adding UFH to bivalirudin did not increase the risk of bleeding. Pre-randomization heparin has been shown as an independent predictor of reducing acute stent thrombosis in both arms of this study . As with most other large randomised trials, important patient subgroups are often excluded. In addition, the use of certain procedural techniques, adjunctive medications and devices often differs between randomised trials and the “real world” experience. Therefore, we aimed to carry out an observational study of primary PCI patients in our centre, to confirm that bivalirudin is truly non-inferior to abciximab in an unselected group of patients.
2
Methods
Primary PCI for STEMI in our unit started in September 2009 and we included all patients who underwent PPCI between September 2009 and November 2011 (inclusive). Our primary PCI service is a full time service with a catchment population of 1.6 million in United Kingdom, led by 10 consultant cardiologists. All PPCI operators are high volume operators performing more than 200 PCI procedures a year. Baseline characteristics and procedural data of all patients were entered prospectively at the time of procedure by qualified cardiac catheterisation laboratory personnel and doctors, into our dedicated cardiac service database system (Phillips CVIS system). For those patients who had more than one PPCI procedure during the study period, only their index procedure details were included for analysis. PCI was done by standard techniques; all patients undergoing PCI were loaded with 600 mg of Clopidogrel and 300 mg of Aspirin prior to the procedure. Use of thrombectomy devices, access site and the type of stent implanted were at the discretion of the operator. All patients received a bolus dose of unfractionated heparin (UFH) immediately after angiography, which is a standard practice in our unit. The dose (70–100 IU/kg with a minimum of 5000 IU) was at the discretion of the operator. Abciximab was the only additional anti-thrombotic agent available in our unit between September 2009 and May 2010; from June 2010, Bivalirudin was also available. In those patients who had abciximab or bivalirudin, the bolus doses were given intravenously in the lab after establishing coronary flow. The selection of either abciximab (0.25 mg/kg bolus followed by 12 h infusion of 0.125 μg/kg/min) or bivalirudin (0.75 mg/kg bolus and 1.75 mg/kg/h infusion for 4 h) was also decided by the operator on a case by case basis. All patients were maintained on aspirin 75 mg/day and clopidogrel 75 mg/day for a minimum period of one year. Other secondary preventative medications were prescribed at the discretion of the operator. The investigation conforms with the principles outlined in the Declaration of Helsinki.
3
Definitions
Hypertension: This includes all patients who were known to have hypertension prior to the index admission, irrespective of whether they were on medication or not.
Diabetes: This includes patient who were known to have Type I or Type II diabetes mellitus and those who were diagnosed with diabetes during the index admission.
Smoker: This includes all patients who were current or ex smokers who stopped smoking within the last year.
Cardiogenic shock: Cardiogenic shock is defined as anyone who is cold and clammy with systolic BP of < 100 mmHg and heart rate of > 100/min.
CTB time: defined as time from the call for help made by the patient/family (paramedic call or attendance to Accident and Emergency department) to the use of first balloon or thrombectomy device or stent.
DTB time: Time interval from the arrival to our unit (PPCI unit) to the use of first balloon or thrombectomy device or stent.
Procedural success was defined as having a thrombectomy device or balloon catheter/stent across the culprit lesion with at-least Thrombolysis in Myocardial Infarction (TIMI) grade 2 flow at the end of procedure.
Non-coronary artery bypass surgery (CABG) major bleeding was defined as having at least one unit of red cell transfusion due to bleeding from any site (including access site) with a haemoglobin drop of at least 2 g/dl. Access related bleed was defined as having at least one unit of red cell transfusion due to bleeding from either radial or femoral site with a haemoglobin drop of at least 2 g/dl. Definite stent thrombosis was defined according to the Academic Research Consortium (ARC) criteria .
3.1
Follow up data and study end points
Mortality data were obtained from National Health Service (NHS) spine Summary Care record (SCR) database, which is a centralised database that gets updated on a weekly basis. This was obtained using automatic flagging for date of death with the unique NHS number available for individual patients. The primary end point was a composite of 30-day mortality, 30-day definite stent thrombosis or non-CABG major bleeding. The secondary end points were procedural success, in- hospital mortality, 30-day mortality, 1-year mortality, 30-day stent thrombosis, non-CABG major bleeding and access related bleeding.
3.2
Statistics
Continuous data are presented as mean ± standard deviation or median with interquartile ranges (IQR) and categorical outcomes are presented as percentages. Categorical outcomes were compared by means of Fisher’s exact test and permutation unpaired t test was used to compare continuous variable between two groups. A p value of < 0.05 was considered to be statistically significant.
Kaplan–Meier methods were used to assess the survival at follow-up; comparisons were made with the log-rank test. A simple binary logistic regression analysis was used initially to identify predictors of mortality. Cox proportional hazards survival analysis was then used to identify the predictors of 30-day mortality via stepwise regression. The following covariates were used in the model: (1) baseline variables — age (years) at operation, sex, diabetes, hypertension, smoker, previous MI, previous CABG, previous PCI, admission time in-hours, and admission time out-of-hours,(2) procedural variables — call to balloon time (min), door to balloon time (min), cardiogenic shock, single vessel PCI, LAD PCI, pre-procedure TIMI flow, drug eluting stents use, femoral access, and thrombectomy device use. The same set of predictors used for the binary logistic regression was offered to the procedure, which searched for models with a small Akaike Information Criterion (AIC). This was achieved using the step AIC function from the statistical package “R” MASS.
4
Results
Of the 1875 patients admitted with suspected STEMI to our unit during the study period, 1471 (78.5%) underwent PPCI. After excluding patients who had both abciximab and bivalirudin during the same procedure (n = 28), we included those who had abciximab (n = 484) or bivalirudin (n = 516) as additional anti-thrombotic agent during PPCI. The remaining 443 patients had neither abciximab nor bivalirudin during their PPCI and were also excluded. Patient demographics for both groups are given in Table 1 . Apart from fewer women in the abciximab group when compared to the bivalirudin group, there were no statistically significant differences in the baseline characteristics between the two groups ( Table 1 ). Patients with cardiogenic shock and thrombectomy device use were also higher in the abciximab group compared to bivalirudin group ( Table 2 ).
| n (%) | Bivalirudin + UFH (n = 516) | Abciximab + UFH (n = 484) | P value |
|---|---|---|---|
| Age in years | |||
| (mean ± SD) | 64 ± 13.9 | 65 ± 13.4 | 0.4 |
| Age > 75 years | 124 (24) | 104 (21.5) | 0.37 |
| Male | 365 (71) | 386 (80) | 0.001 |
| Diabetes | 47 (9) | 61 (13) | 0.08 |
| Hypertension | 192 (37) | 184 (38) | 0.8 |
| Smoking | 340 (66) | 311 (64) | 0.6 |
| Previous MI | 44 (9) | 55 (11) | 0.14 |
| Previous CABG | 5 (1) | 11 (2) | 0.13 |
| Previous PCI | 32 (6) | 36(7) | 0.45 |
| Admission Time | |||
| In hours (8 am to 6 pm) | 225 (44) | 192 (40) | 0.22 |
| Out of hours (6 pm to 8 am) | 136 (26) | 128 (26) | 1.0 |
| Weekends + BHs | 155 (30) | 164 (34) | 0.2 |
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