Results
Patients
A total of 2198 patients (1089 in the bivalirudin group and 1109 in the control group) provided formal informed consent and comprised the ITT population. A breakdown of GPI use by treatment arm is presented in Figure 1. In the control arm, 649 (58.5%) patients received routine GPI and 460 (41.5%) did not. In the routine GPI group, GPI treatment was initiated in the ambulance in 68% and during coronary angiography in 32% of patients. Of the 460 patients who did not receive routine use of a GPI, 117 (25.4%) patients received it as bailout during PCI and most frequently due to the presence of giant thrombus. In the bivalirudin group, 1047 (96%) patients did not receive a routine GPI, while 42 (3.9%) patients did, despite the fact that this was a deviation from the protocol. Of the 1047 patients who did not receive routine GPI, 83 (7.9%) received it as bailout also more commonly due to the presence of giant thrombus.
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Figure 1.
GPI use by randomized treatment group. GPI, glycoprotein IIb/IIIa inhibitor; ITT, intent-to-treat; LMWH, low-molecular-weight heparin; UFH, unfractionated heparin.
The baseline characteristics of patients in the three groups were generally well matched between the groups, although there was a higher rate of hypertension and lower rates of Killip class II–IV and creatinine clearance ≤60 mL/min in the heparins with routine GPI use treatment group compared with the heparins with bailout GPI use group (Table 1).
Procedures and Treatments
Study medications and procedural details are presented in Table 2. Enoxaparin was used in 51/649 (8%) and 43/460 (9%) of patients treated with routine or with bailout GPI, respectively. A similar percentage of patients in each group received a loading dose of a P2Y12 inhibitor, with clopidogrel as the most frequently given agent. A significantly higher percentage of patients in the heparins plus bailout GPI group received prasugrel compared with the heparins plus routine GPI group. Conversely, ticagrelor was more commonly given to patients in the heparins plus routine GPI compared with heparins with bailout GPI group.
Femoral artery access, drug-eluting stent use, and the presence of single-vessel disease were all more common in the heparins plus routine GPI group, while pre-PCI TIMI flow of 0 or 1 was more frequent among the heparins with bailout GPI patients.
Outcomes
Comparisons of unadjusted event rates between the three treatment groups are shown in Table 3. Among patients treated with heparins, there were no significant differences observed in the rates of either the primary or key secondary outcomes according to the use of GPI. The composite of ischaemic events (MACE), however, was significantly lower in patients treated with heparins plus routine GPI compared with patients treated with heparin and bailout GPI (4.3 vs. 7.2%, P = 0.04). In the comparison between bivalirudin and either of the heparins arms the results were consistent with the overall results of the main trial. Specifically, bivalirudin resulted in significantly lower rates of the primary outcome and protocol major bleeding (Table 3, Figure 2), as well as a higher rate of stent thrombosis. After adjustment, the benefit of bivalirudin over heparins with bailout GPI for the primary outcome, major bleeding, and NACE was maintained (Figures 3 and 4).
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Figure 2.
Kaplan–Meier curves of the primary composite endpoint. GPI, glycoprotein IIb/IIIa inhibitor.
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Figure 3.
Unadjusted outcomes of bivalirudin vs. heparins + bailout GPI. ARC, Academic Research Consortium; GPI, glycoprotein IIb/IIIa inhibitor; IDR, ischaemia-driven revascularization; MACE, major adverse cardiac events; MI, myocardial infarction; NACE, net adverse clinical events.
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Figure 4.
Adjusted ORs of bivalirudin vs. heparin + bailout GPI. GPI, glycoprotein IIb/IIIa inhibitor; IDR, ischaemia-driven revascularization; MACE, major adverse cardiac events; MI, myocardial infarction; NACE, net adverse clinical events.
A total of 94 patients in the control group received enoxaparin, 62 (66%) of the latter were treated with routine GPI. The rates of the primary endpoint were not different between the patients treated with enoxaparin and UFH (9.6 vs. 8.2%, odds ratio 1.16, 95% CI 0.60–2.24, P-value) (see Supplementary material online, Table S1http://eurheartj.oxfordjournals.org/content/35/36/2460/suppl/DC1).