Securing the Future for a Major Academic Cardiovascular Program: Hardwiring a Referral Network and Preparing for a Transition to Value-Based Reimbursement.

The University of Kentucky College of Medicine and Albert B. Chandler Hospital opened over 50 years ago to serve Kentucky. After initial growth and expansion, both were struggling clinically, academically, and financially in the early 2000s. Difficulties were apparent in cardiovascular (CV) services, which captured only 11% of the regional patients hospitalized for cardiac disease. Over the next 15 years, CV services dynamically transformed to become the leading provider with a large network of regional partners, garnering 42% of market share. This article describes strategic plans and initiatives leading to clinical and academic growth. Future value-based initiatives are also described.

Tailoring Antiplatelet Therapy Intensity to Ischemic and Bleeding Risk.

BACKGROUND: Balancing ischemic and bleeding risk is an evolving framework. METHODS AND RESULTS: Our objectives were to simulate changes in risks for adverse events and event-driven costs with use of ticagrelor or prasugrel versus clopidogrel according to varying levels of ischemic and bleeding risk. Using the validated PARIS risk functions, we estimated 1-year ischemic (myocardial infarction or stent thrombosis) and bleeding (Bleeding Academic Research Consortium types 3 or 5) event rates among PARIS study participants who underwent percutaneous coronary intervention with drug-eluting stent implantation for an acute coronary syndrome and were discharged with aspirin and clopidogrel (n=1497). Simulated changes in adverse events with ticagrelor or prasugrel were calculated by applying treatment effects from randomized trials for a 1-year time horizon. Event costs were estimated using National Inpatient Sample data. Net costs were calculated between antiplatelet therapy groups according to level of ischemic and bleeding risk. After weighting events for quality-of-life impact, we calculated event rates and costs for risk-tailored treatment versus clopidogrel under multiple drug pricing assumptions. One-year rates (per 1000 person-years) for ischemic events were 12.6, 24.1, and 66.1, respectively, among those at low (n=630), intermediate (n=536), and high (n=331) ischemic risk. Analogous bleeding rates were 11.0, 23.9, and 66.2, respectively, among low (n=728), intermediate (n=634), and high (n=135) bleeding risk patients. Mean per event costs were $22 174 (ischemic) and $12 203 (bleeding). When risks for ischemia matched or exceeded bleeding, simulated utility-weighted event rates favored ticagrelor/prasugrel, whereas clopidogrel reduced utility-weighted events when bleeding exceeded ischemic risk. One-year costs were sensitive to drug pricing assumptions, and risk-tailored treatment with either agent progressed from cost incurring to cost saving with increasing generic market share. CONCLUSIONS: Tailoring antiplatelet therapy intensity to patient risk may improve health utility and could produce cost savings in the first year after percutaneous coronary intervention. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov . Unique identifier: NCT00998127.

Lack of Concordance Between Local Investigators, Angiographic Core Laboratory, and Clinical Event Committee in the Assessment of Stent Thrombosis: Results From the TRACER Angiographic Substudy.

BACKGROUND: Stent thrombosis (ST) is an important end point in cardiovascular clinical trials. Adjudication is traditionally based on clinical event committee (CEC) review of case report forms and source documentation rather than angiograms. However, the degree to which this method of adjudication is concordant with the review of independent angiographic core laboratories (ACLs) has not been studied. This report represents the first assessment of variability between local investigators (LIs), a CEC, and an ACL. METHODS AND RESULTS: Serial angiograms of 329 patients with acute coronary syndrome without ST-segment-elevation who underwent percutaneous coronary intervention at entry in the Trial to Assess the Effects of Vorapaxar in Preventing Heart Attack and Stroke in Particpants With Acute Coronary Syndrome (TRACER) and who met criteria for possible ST subsequent to the index event were reviewed by an ACL. The ACL was blinded to the assessment by both LIs and the CEC regarding the presence or absence of ST. CEC adjudication was based on Academic Research Consortium definitions of ST, using case report form data and source documents, including catheterization laboratory reports. The ACL, CEC, and LIs agreed on the presence or absence of ST in 52.9% events (κ=0.32; 95% confidence interval, 0.26-0.39). The ACL and CEC agreed on 82.7% of events (κ=0.57; 95% confidence interval, 0.47-0.67); the ACL and LIs agreed on 61.1% of events (κ=0.25; 95% confidence interval, 0.16-0.34); and the CEC and LIs agreed on 62% of events (κ=0.28; 95% confidence interval, 0.21-0.36). CONCLUSIONS: ST reporting by an ACL, a CEC, and LIs is discordant. The assessment of ST is more often detected by direct review of angiograms by an ACL. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00527943.

A randomized two-by-two comparison of high-dose bolus tirofiban versus abciximab and unfractionated heparin versus bivalirudin during percutaneous coronary revascularization and stent placement: the tirofiban evaluation of novel dosing versus abciximab with clopidogrel and inhibition of thrombin (TENACITY) study trial.

BACKGROUND: In the absence of high-dose thienopyridines, placebo-controlled trials have demonstrated a reduction in ischemic events with intravenous glycoprotein IIb/IIIa antagonists during percutaneous coronary intervention (PCI). One head-to-head trial comparing abciximab and tirofiban among PCI patients found tirofiban to be inferior, and laboratory evidence confirmed that the bolus dose of tirofiban tested in that trial to be less effective than abciximab. Whether a higher bolus dose of tirofiban would be as efficacious as abciximab during PCI is uncertain. METHODS AND RESULTS: Patients undergoing PCI were randomized equally to abciximab or to tirofiban, given as high-dose bolus (25 µg/kg) plus 12-hr infusion (0.15 µg/kg/min). All patients received aspirin and clopidogrel and were additionally randomized to unfractionated heparin or bivalirudin. Approximately 8,000 patients were to be studied, but after 383 were enrolled, the study sponsor discontinued the trial for financial reasons. The primary endpoint of 30-day death, myocardial infarction, or urgent target vessel revascularization occurred in 8.8% of patients randomized to abciximab and 6.9% of those randomized to tirofiban. The respective rates of major bleeding were 1.5 and 1.6%. Additionally, the primary endpoint occurred in 8.1% of patients randomized to unfractionated heparin and 7.6% of those randomized to bivalirudin. The respective rates of major bleeding were 2.5% and 0.5%. CONCLUSION: With limited assessment, this direct comparison of high-dose bolus tirofiban versus abciximab produced encouraging results and suggests that further study of this tirofiban dose regimen is warranted. The limited assessments comparing heparin and bivalirudin are consistent with prior observations.

Is there an association between external cardioversions and long-term mortality and morbidity? Insights from the Atrial Fibrillation Follow-up Investigation of Rhythm Management study.

BACKGROUND: Cardiac electric therapies effectively terminate tachyarrhythmias. Recent data suggest a possible increase in long-term mortality associated with implantable cardioverter-defibrillator shocks. Little is known about the association between external cardioversion episodes (ECVe) and long-term mortality. We sought to assess the safety of repeated ECVe with regard to cardiovascular mortality and morbidity. METHODS AND RESULTS: We analyzed the data of the 4060 patients from the AFFIRM (Atrial Fibrillation Follow-up Investigation of Rhythm Management) trial. In particular, associations of ECVe with all-cause mortality, cardiovascular mortality, and hospitalizations after ECVe were studied. Over an average follow-up of 3.5 years, 660 (16.3%) patients died, 331 (8.2%) from cardiovascular causes. A total of 207 (5.1%) and 1697 (41.8%) patients had low ejection fraction and nonparoxysmal atrial fibrillation, respectively; 2460 patients received no ECVe, whereas 1600 experienced ≥ 1 ECVe. Death occurred in 412 (16.7%), 196 (16.5%), 39 (13.5%), and 13 (10.4%) of patients with 0, 1, 2, and ≥ 3 ECVe, respectively. There was no significant association between ECVe and mortality within any of the 4 subgroups defined by ejection fraction and atrial fibrillation type, although myocardial infarction, coronary artery bypass graft, and digoxin were significantly associated with death (estimated hazard ratios, 1.65, 1.59, and 1.62, respectively; P < 0.0001). ECVe were associated with increased cardiac hospitalization reported at the next follow-up visit (39.3% versus 5.8%; estimated odds ratio, 1.39; P < 0.0001). CONCLUSIONS: In the AFFIRM study, there was no significant association between ECVe and long-term mortality, even though ECVe were associated with increased hospitalizations from cardiac causes. Digoxin, myocardial infarction, and coronary artery bypass graft were significantly associated with mortality.

Contribution of angiographic and electrocardiographic parameters of reperfusion to prediction of mortality and morbidity after acute ST-elevation myocardial infarction: Insights from the Assessment of Pexelizumab in Acute Myocardial Infarction trial.

BACKGROUND: Reperfusion with primary percutaneous intervention (PCI) in ST-segment elevation myocardial infarction leads to improved clinical outcomes. The contribution angiographic vs electrocardiographic reperfusion parameters confer on prognosis is unclear. METHODS: A prespecified subset of the APEX-AMI trial patients was analyzed by independent angiographic and electrocardiographic core laboratories (n = 1,018). Angiographic reperfusion after PCI and electrocardiogram 30 minutes post-PCI were assessed. RESULTS: Of the 941 patients in the angiographic substudy, 796 (85%) attained post-PCI Thrombolysis In Myocardial Infarction (TIMI) flow 3 and 852 (91%) had TIMI Myocardial Perfusion Grade (TMPG) 2/3. There were 664 (71%) patients with residual ST elevation (ST-E) <2 mm. Ninety-day mortality and death/CHF/shock were lower in patients with TIMI flow 3 vs <3 (1.9% vs 6.2%, P = .002; 5.8% vs 10.4%, P = .044) and those with TMPG 2/3 vs 0/1 (2.0% vs 7.9%, P = .001; 6.0% vs 11.9%, P = .028). Patients with residual ST-E <2 mm had similar rates of mortality as those with > or =2 mm (2.3% vs 3.3%, P = .374) but lower rates of death/CHF/shock (5.2% vs 9.6%, P = .013). After multivariable adjustment, only post-PCI TMPG 2/3 was significantly associated with survival (P = .001), whereas residual ST-E (P = .606) and post-PCI TIMI flow grade (P = .086) were not. Conversely, residual ST-E > or =2 mm (P = .012) rather than angiographic reperfusion was associated with the composite of death/CHF/shock events. CONCLUSION: Angiographic and electrocardiographic estimates of reperfusion with primary PCI in ST-segment elevation myocardial infarction provide different and complementary predictions of morbidity and mortality.

Non-invasive assessment of plaque morphology and remodeling in mildly stenotic coronary segments: comparison of 16-slice computed tomography and intravascular ultrasound.

BACKGROUND: Non-invasive identification and characterization of mildly stenotic atherosclerotic lesions is an increasingly important focus of coronary imaging. DESIGN: We examined the accuracy of multi (16)-slice computed tomography (MSCT) for imaging of these lesions in comparison with intravascular ultrasound (IVUS). MATERIALS: Mildly stenotic segments of the left coronary artery were identified by coronary angiography and analyzed using IVUS and contrast-enhanced MSCT. Independent reviewers evaluated the accuracy of MSCT for presence, composition and distribution of atherosclerotic plaque and remodeling response in comparison to IVUS using receiver operating characteristic (ROC) data analysis. RESULTS: Of 46 segments in 14 patients, diagnostic characterization by MSCT was possible in 37 (80.4%) segments. In these segments the accuracy of MSCT for identifying plaque presence, calcification, distribution and positive remodeling was consistently greater than 0.90 (reader 1) and 0.87 (reader 2). CONCLUSION: State-of-the-art MSCT can accurately identify mildly stenotic coronary atherosclerosis and provide an assessment of morphology and remodeling response.