Benefit and Risks of Aspirin in Addition to Ticagrelor in Acute Coronary Syndromes:A Post Hoc Analysis of the Randomized GLOBAL LEADERS Trial

Key PointsQuestionWhat are the benefits and risks of continuing aspirin in addition to P2Y12 receptor inhibition with ticagrelor among patients with acute coronary syndrome between 1 month and 12 months after percutaneous coronary intervention? FindingsIn this nonprespecified, post hoc analysis of the GLOBAL LEADERS randomized clinical trial, beyond 1 month after percutaneous coronary intervention in acute coronary syndrome, aspirin was associated with increased bleeding risk and appeared not to add to the benefit of ticagrelor on ischemic events. MeaningThe findings of this hypothesis-generating analysis pave the way for further trials evaluating aspirin-free antiplatelet strategies after percutaneous coronary intervention. ImportanceThe role of aspirin as part of antiplatelet regimens in acute coronary syndromes (ACS) needs to be clarified in the context of newer potent P2Y12 antagonists. ObjectiveTo evaluate the benefit and risks of aspirin in addition to ticagrelor among patients with ACS beyond 1 month after percutaneous coronary intervention (PCI). Design, Setting, and ParticipantsThis is a nonprespecified, post hoc analysis of GLOBAL LEADERS, a randomized, open-label superiority trial comparing 2 antiplatelet treatment strategies after PCI. The trial included 130 secondary/tertiary care hospitals in different countries, with 15991 unselected patients with stable coronary artery disease or ACS undergoing PCI. Patients had outpatient visits at 1, 3, 6, 12, 18, and 24 months after index procedure. InterventionsThe experimental group received aspirin plus ticagrelor for 1 month followed by 23-month ticagrelor monotherapy; the reference group received aspirin plus either clopidogrel (stable coronary artery disease) or ticagrelor (ACS) for 12 months, followed by 12-month aspirin monotherapy. In this analysis, we examined the clinical outcomes occurring between 31 days and 365 days after randomization, specifically in patients with ACS who, within this time frame, were assigned to receive either ticagrelor alone or ticagrelor and aspirin. Main Outcomes and MeasuresThe primary outcome was the composite of all-cause death or new Q-wave myocardial infarction. ResultsOf 15968 participants, there were 7487 patients with ACS enrolled; 3750 patients were assigned to the experimental group and 3737 patients to the reference group. Between 31 and 365 days after randomization, the primary outcome occurred in 55 patients (1.5%) in the experimental group and in 75 patients (2.0%) in the reference group (hazard ratio [HR], 0.73; 95% CI, 0.51-1.03; P=.07); investigator-reported Bleeding Academic Research Consortium-defined bleeding type 3 or 5 occurred in 28 patients (0.8%) in the experimental group and in 54 patients (1.5%) in the reference arm (HR, 0.52; 95% CI, 0.33-0.81; P=.004). Conclusions and RelevanceBetween 1 month and 12 months after PCI in ACS, aspirin was associated with increased bleeding risk and appeared not to add to the benefit of ticagrelor on ischemic events. These findings should be interpreted as exploratory and hypothesis generating; however, they pave the way for further trials evaluating aspirin-free antiplatelet strategies after PCI. Trial RegistrationClinicalTrials.gov identifier: NCT01813435. This secondary analysis of the GLOBAL LEADERS randomized clinical trial evaluates the benefit and risks of aspirin in addition to ticagrelor among patients with acute coronary syndrome beyond 1 month after percutaneous coronary intervention

Real world impact of added FFR-CT to coronary CT angiography on clinical decision-making and patient prognosis – IMPACT FFR study

Objectives: The addition of CT-derived fractional flow reserve (FFR-CT) increases the diagnostic accuracy of coronary CT angiography (CCTA). We assessed the impact of FFR-CT in routine clinical practice on clinical decision-making and patient prognosis in patients suspected of stable coronary artery disease (CAD). Methods: This retrospective, single-center study compared a cohort that received CCTA with FFR-CT to a historical cohort that received CCTA before FFR-CT was available. We assessed the clinical management decisions after FFR-CT and CCTA and the rate of major adverse cardiac events (MACEs) during the 1-year follow-up using chi-square tests for independence. Kaplan–Meier curves were used to visualize the occurrence of safety outcomes over time. Results: A total of 360 patients at low to intermediate risk of CAD were included, 224 in the CCTA only group, and 136 in the FFR-CT group. During follow-up, 13 MACE occurred in 12 patients, 9 (4.0%) in the CCTA group, and three (2.2%) in the FFR-CT group. Clinical management decisions differed significantly between both groups. After CCTA, 60 patients (26.5%) received optimal medical therapy (OMT) only, 115 (51.3%) invasive coronary angiography (ICA), and 49 (21.9%) single positron emission CT (SPECT). After FFR-CT, 106 patients (77.9%) received OMT only, 27 (19.9%) ICA, and three (2.2%) SPECT (p < 0.001 for all three options). The revascularization rate after ICA was similar between groups (p = 0.15). However, patients in the CCTA group more often underwent revascularization (p = 0.007). Conclusion: Addition of FFR-CT to CCTA led to a reduction in (invasive) diagnostic testing and less revascularizations without observed difference in outcomes after 1 year. Key Points: • Previous studies have shown that computed tomography–derived fractional flow reserve improves the accuracy of coronary computed tomography angiography without changes in acquisition protocols. • This study shows that use of computed tomography-derived fractional flow reserve as gatekeeper to invasive coronary angiography in patients suspected of stable coronary artery disease leads to less invasive testing and revascularization without observed difference in outcomes after 1 year. • This could lead to a significant reduction in costs, complications and (retrospectively unnecessary) usage of diagnostic testing capacity, and a significant increase in patient satisfaction

Association between post-percutaneous coronary intervention bivalirudin infusion and net adverse clinical events: a post hoc analysis of the GLOBAL LEADERS study

AIMS The efficacy and safety of continued bivalirudin infusion after percutaneous coronary intervention (PCI) remains uncertain. We sought to investigate the association between post-PCI bivalirudin infusion and the risk of net adverse clinical events (NACE) at 30 days. METHODS AND RESULTS In the GLOBAL LEADERS study, all patients who received bivalirudin during PCI were categorized according to the use of bivalirudin infusion after the procedure. The primary endpoint of the present analysis was NACE [a composite of all-cause death, any stroke, any myocardial infarction, all revascularization, and bleeding assessed according to the Bleeding Academic Research Consortium (BARC) criteria Type 3 or 5] at 30 days. The key safety endpoint was BARC Type 3 or 5 bleeding and definite stent thrombosis. Of 15 968 patients, 13 870 underwent PCI with the use of bivalirudin. In total, 7148 patients received continued bivalirudin infusion after procedure, while 6722 patients received standard care. After propensity score covariate adjustment, the risk of NACE did not significantly differ between two treatments after PCI [continued bivalirudin infusion vs. no bivalirudin infusion: 3.2% vs. 3.1%, adjusted hazard ratio (aHR) 1.35, 95% confidence interval (CI) 0.99-1.84, P = 0.06] nor the BARC Type 3 or 5 bleeding (0.7% vs. 0.7%, aHR 0.89, 95% CI 0.44-1.79; P = 0.743) and definite stent thrombosis (0.5% vs. 0.3%, aHR 1.71, 95% CI 0.77-3.81, P = 0.189). However, continued bivalirudin infusion was associated with an increased risk of NACE and definite stent thrombosis in ST-elevation myocardial infarction (STEMI) patients. CONCLUSION In an all-comers population undergoing PCI, there was no significant difference in the risk of NACE at 30 days between continued bivalirudin infusion vs. no bivalirudin infusion after procedure but continued bivalirudin infusion was associated with a higher risk of NACE in STEMI patients when compared with no infusion