Faculty Bibliography

BACKGROUND: The optimal revascularization strategy in patients with acute coronary syndrome (ACS) and proximal left anterior descending (pLAD) coronary artery lesions is not well defined. The aim of this study was to compare the outcomes of ACS patients with pLAD culprit lesions receiving percutaneous coronary intervention (PCI) vs coronary artery bypass graft (CABG). METHODS: The ACUITY trial was a multicenter, prospective trial of patients with ACS treated with an early invasive strategy. Major adverse cardiac event (MACE; defined as death, myocardial infarction [MI], and repeat revascularization) and stroke were compared at 30 days and 1 year between PCI and CABG in patients with significant stenosis of the pLAD undergoing revascularization. Postprocedural major bleeding was evaluated at 30 days. RESULTS: Among patients with a significant pLAD stenosis (n = 842), a total of 562 (66.7%) underwent PCI and 280 (33.3%) underwent CABG. Baseline characteristics, including age, sex, diabetes, and TIMI risk score, were well matched between groups; however, patients undergoing PCI were more likely to have had previous CABG (21.9% vs 6.4%; P<.001). Death, MI, MACE, and stroke rates did not differ between groups at 1 year. PCI patients had lower bleeding rates (8.1% vs 52.4%; P<.001) and blood product transfusion at 30 days (4.5% vs 41.3%; P<.001), but higher rates of unplanned revascularization at 1 year (12.7% vs 5.2%; P<.01). These results were consistent in patients with single vs multivessel disease and in diabetics vs non-diabetics. CONCLUSIONS: Among ACS patients with pLAD culprit lesions, an initial revascularization strategy of PCI compared with CABG yields similar 1-year death, MI, and MACE rates, although unplanned revascularization is more common after PCI.

BACKGROUND: The preferred revascularization strategy for diabetic patients with acute coronary syndromes and multivessel coronary artery disease is uncertain. We evaluated the outcomes of diabetic patients with moderate and high-risk acute coronary syndrome and multivessel disease managed with percutaneous coronary intervention (PCI) versus coronary artery bypass grafting (CABG). METHODS AND RESULTS: Among 13 819 moderate and high-risk acute coronary syndrome patients enrolled in the Acute Catheterization and Early Intervention Triage Strategy (ACUITY) trial, 1772 diabetic patients had multivessel disease with left anterior descending artery involvement and were managed by PCI (n=1349) or CABG (n=423). Propensity scoring was applied to adjust for differences in baseline clinical and angiographic characteristics, yielding a total of 326 matched patients (163 managed by PCI and 163 managed by CABG). At 30 days, treatment with PCI compared with CABG was associated with lower rates of major bleeding (15.3% versus 55.6%; P<0.0001), blood transfusions (9.2% versus 43.2%; P<0.0001), and acute kidney injury (13.4% versus 33.6%; P<0.0001), but more unplanned revascularization procedures (6.9% versus 1.9%; P=0.03). At 1 year PCI was associated with higher rates of repeat revascularization procedures (19.5% versus 5.2%; P=0.0001), with nonsignificantly different rates of myocardial infarction, stroke, and death at either 30 days or 1 year. CONCLUSIONS: In the large-scale ACUITY trial, diabetic patients with acute coronary syndrome and multivessel disease treated with PCI rather than CABG had less bleeding and acute kidney injury, greater need for repeat revascularization procedures, and comparable rates of myocardial infarction, stroke, and death through 1-year follow-up. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00093158.

BACKGROUND: COURAGE and BARI-2D have questioned the utility of routine revascularization for the prevention of cardiovascular events in patients with stable ischemic heart disease (SIHD). On the other end of the spectrum, a routine invasive strategy in patients with acute coronary syndrome (ACS) is superior to a conservative strategy. The impact of the above trials on the trend in percutaneous coronary intervention (PCI) volume for SIHD and ACS is not known. METHODS: Data from the 2001-2011 Nationwide Inpatient Sample for discharges with PCI were used. The trend in PCI volume over time was analyzed, especially in relation to the COURAGE (2007) and the BARI-2D (2009) trials. Age and gender adjusted PCI rates were calculated using direct standardization method. RESULTS: Among the 8,150,764 PCI procedures, there was a steady increase in PCI volumes until the publication of the COURAGE/BARI-2D trials after which the volume decreased. Compared to the peak volume of 909,331 in 2006, PCI volume declined by 38% to 562,036 in 2011 (P<0.0001); driven by a 60% decrease in PCI for SIHD from 409,199 in 2006 to 160,707 in 2011 (P<0.0001). Moreover, there was a 20% decrease in PCI for ACS from 500,132 in 2006 to 401,330 in 2011 (P<0.0001) driven by a significant decrease in PCI for unstable angina. Results were similar in diabetics with a decline in the volume after BARI-2D trial, although the decline was less dramatic. CONCLUSION: The 11-year trend indicates a substantial impact of COURAGE/BARI-2D on SIHD PCI volumes with an unintended consequence of lower PCI volumes for ACS.

There are limited data on the impact of anemia on clinical outcomes in unstable angina and non-ST-segment elevation myocardial infarction treated with an early invasive strategy. We sought to determine the short- and long-term clinical events among patients with and without anemia enrolled in the Acute Catheterization and Urgent Intervention Triage Strategy (ACUITY) trial. Anemia was defined as baseline hemoglobin of <13 g/dl for men and <12 g/dl for women. The primary end points were composite ischemia (death, myocardial infarction, or unplanned revascularization for ischemia) and major bleeding assessed in-hospital, at 1 month, and at 1 year. Among the 13,819 patients in the ACUITY trial, information regarding anemia was available in 13,032 (94.3%), 2,199 of whom (16.9%) had anemia. Patients with anemia compared with those without anemia had significantly increased adverse event rates in-hospital (composite ischemia 6.6% vs 4.8%, p = 0.0004; major bleeding 7.3% vs 3.3%, p <0.0001), at 1 month (composite ischemia 10% vs 7.2%, p <0.0001, major bleeding 8.8% vs 3.9%, p <0.0001), and 1 year (composite ischemia 21.7% vs 15.3%, p <0.0001). Anemia was an independent predictor of death at 1 year (hazard ratio 1.77, 95% confidence interval [CI] 1.29 to 2.44, p = 0.0005). Composite ischemia was significantly more common among patients who developed in-hospital non-coronary artery bypass surgery major bleeding compared with those who did not (anemic patients 1-year relative risk 2.19, 95% CI 1.67 to 2.88, p <0.0001; nonanemic patients relative risk 2.16, 95% CI 1.76 to 2.65, p <0.0001). In conclusion, in the ACUITY trial, baseline anemia was strongly associated with adverse early and late clinical events, especially in those who developed major bleeding.

Although lesion complexity is predictive of outcomes after balloon angioplasty, it is unclear whether complex lesions continue to portend a worse prognosis in patients with acute coronary syndrome (ACS) undergoing percutaneous coronary intervention (PCI) with contemporary interventional therapies. We sought to assess the impact of angiographic lesion complexity, defined by the modified American College of Cardiology/American Heart Association classification, on clinical outcomes after PCI in patients with ACS and to determine whether an interaction exists between lesion complexity and antithrombin regimen outcomes after PCI. Among the 3,661 patients who underwent PCI in the Acute Catheterization and Urgent Intervention Triage strategy study, patients with type C lesions (n = 1,654 [45%]) had higher 30-day rates of mortality (1.2% vs 0.6%, p = 0.049), myocardial infarction (9.2% vs 6.3%, p = 0.0006), and unplanned revascularization (4.3% vs 3.1%, p = 0.04) compared with those without type C lesions. In multivariate analysis, type C lesions were independently associated with myocardial infarction (odds ratio [95% confidence interval] = 1.37 [1.04 to 1.80], p = 0.02) and composite ischemia (odds ratio [95% confidence interval] = 1.49 [1.17 to 1.88], p = 0.001) at 30 days. Bivalirudin monotherapy compared with heparin plus a glycoprotein IIb/IIIa inhibitor reduced major bleeding complications with similar rates of composite ischemic events, regardless of the presence of type C lesions. There were no interactions between antithrombotic regimens and lesion complexity in terms of composite ischemia and major bleeding (p [interaction] = 0.91 and 0.80, respectively). In conclusion, patients with ACS with type C lesion characteristics undergoing PCI have an adverse short-term prognosis. Treatment with bivalirudin monotherapy reduces major hemorrhagic complications irrespective of lesion complexity with comparable suppression of adverse ischemic events as heparin plus glycoprotein IIb/IIIa inhibitor.

OBJECTIVES: To investigate the relative benefits of unfractionated heparin, low molecular weight heparin(LMWH), fondaparinux, and bivalirudin as treatment options for patients with ST segment elevation myocardial infarction undergoing percutaneous coronary intervention (PCI). DESIGN: Mixed treatment comparison and direct comparison meta-analysis of randomized trials in the era of stents and P2Y12 inhibitors. DATA SOURCES AND STUDY SELECTION: A search of Medline, Embase, Cochrane Central Register of Controlled Trials (CENTRAL) for randomized trials comparing unfractionated heparin plus glycoprotein IIb/IIIa inhibitor(GpIIb/IIIa inhibitor), unfractionated heparin, bivalirudin, fondaparinux, or LMWH plus GpIIb/IIIa inhibitor for patients undergoing primary PCI. OUTCOMES: The primary efficacy outcome was short term (in hospital or within 30 days) major adverse cardiovascular event; the primary safety outcome was short term major bleeding. RESULTS: We identified 22 randomized trials that enrolled 22 434 patients. In the mixed treatment comparison models, when compared with unfractionated heparin plus GpIIb/IIIa inhibitor, unfractionated heparin was associated with a higher risk of major adverse cardiovascular events (relative risk 1.49 (95% confidence interval 1.21 to 1.84), as were bivalirudin (relative risk 1.34 (1.01 to 1.78)) and fondaparinux (1.78 (1.01 to 3.14)). LMWH plus GpIIb/IIIa inhibitor showed highest treatment efficacy, followed (in order) by unfractionated heparin plus GpIIb/IIIa inhibitor, bivalirudin, unfractionated heparin, and fondaparinux. Bivalirudin was associated with lower major bleeding risk compared with unfractionated heparin plus GpIIb/IIIa inhibitor (relative risk 0.47 (0.30 to 0.74)) or unfractionated heparin (0.58 (0.37 to 0.90)). Bivalirudin, followed by unfractionated heparin, LMWH plus GpIIb/IIIa inhibitor, unfractionated heparin plus GpIIb/IIIa inhibitor, and fondaparinux were the hierarchy for treatment safety. Results were similar in direct comparison meta-analyses: bivalirudin was associated with a 39%, 44%, and 65% higher risk of myocardial infarction, urgent revascularization, and stent thrombosis respectively when compared with unfractionated heparin with or without GpIIb/IIIa inhibitor. However, bivalirudin was associated with a 48% lower risk of major bleeding compared with unfractionated heparin plus GpIIb/IIIa inhibitor and 32% lower compared with unfractionated heparin alone. CONCLUSIONS: In patients undergoing primary PCI, unfractionated heparin plus GpIIb/IIIa inhibitor and LMWH plus GpIIb/IIIa inhibitor were most efficacious, with the lowest rate of major adverse cardiovascular events, whereas bivalirudin was safest, with the lowest bleeding. These relationships should be considered in selecting anticoagulant therapies in patients undergoing primary PCI.