Levosimendan in patients with reduced left ventricular function undergoing isolated coronary or valve surgery.

OBJECTIVE: In the Levosimendan in Patients with Left Ventricular Systolic Dysfunction Undergoing Cardiac Surgery Requiring Cardiopulmonary Bypass (LEVO-CTS) trial, no differences in clinical outcomes were observed between levosimendan and placebo in a broad population of patients undergoing cardiac surgery. In previous studies, the benefits of levosimendan were most clearly evident in patients undergoing isolated coronary artery bypass grafting (CABG) surgery. In a prespecified analysis of LEVO-CTS, we compared treatment-related outcomes and costs across types of cardiac surgical procedures. METHODS: Overall, 563 (66.4%) patients underwent isolated CABG, 97 (11.4%) isolated valve, and 188 (22.2%) combined CABG/valve surgery. Outcomes included the co-primary 4-component composite (30-day mortality, 30-day renal replacement, 5-day myocardial infarction, or 5-day mechanical circulatory support), the 2-component composite (30-day mortality or 5-day mechanical circulatory support), 90-day mortality, low cardiac output syndrome (LCOS), and 30-day medical costs. RESULTS: The 4- and 2-component outcomes were not significantly different with levosimendan and placebo in patients undergoing CABG (15.2% vs 19.3% and 7.8% vs 10.4%), valve (49.0% vs 33.3% and 22.4% vs 2.1%), or combined procedures (39.6% vs 35.9% and 24.0% vs 19.6%). Ninety-day mortality was lower with levosimendan in isolated CABG (2.1% vs 7.9%; hazard ratio [HR], 0.26; 95% confidence interval [CI], 0.11-0.64), but not significantly different in valve (8.3% vs 2.0%; HR, 4.10; 95% CI, 0.46-36.72) or combined procedures (10.4% vs 7.6%; HR, 1.39; 95% CI, 0.53-3.64; interaction P = .011). LCOS (12.0% vs 22.1%; odds ratio, 0.48; 95% CI, 0.30-0.76; interaction P = .118) was significantly lower in levosimendan-treated patients undergoing isolated CABG. Excluding study drug costs, median and mean 30-day costs were $53,707 and $65,852 for levosimendan and $54,636 and $67,122 for placebo, with a 30-day mean difference (levosimendan - placebo) of -$1270 (bootstrap 95% CI, -$8722 to $6165). CONCLUSIONS: Levosimendan was associated with lower 90-day mortality and LCOS in patients undergoing isolated CABG, but not in those undergoing isolated valve or combined CABG/valve procedures.

Acute and 1-Year Hospitalization Costs for Acute Myocardial Infarction Treated With Percutaneous Coronary Intervention: Results From the TRANSLATE-ACS Registry.

Background Hospitalization for acute myocardial infarction (MI) in the United States is both common and expensive, but those features alone provide little insight into cost-saving opportunities. Methods and Results To understand the cost drivers during hospitalization for acute MI and in the following year, we prospectively studied 11 969 patients with acute MI undergoing percutaneous coronary intervention at 233 US hospitals (2010-2013) from the TRANSLATE-ACS (Treatment With ADP Receptor Inhibitors: Longitudinal Assessment of Treatment Patterns and Events After Acute Coronary Syndrome) registry. Baseline costs were collected in a random subset (n=4619 patients, 54% ST-segment-elevation MI [STEMI]), while follow-up costs out to 1 year were collected for all patients. The mean index length of stay was 3.1 days (for both STEMI and non-STEMI) and mean intensive care unit length of stay was 1.2 days (1.4 days for STEMI and 1.0 days for non-STEMI). Index hospital costs averaged $18 931 ($19 327 for STEMI, $18 465 for non-STEMI), with 45% catheterization laboratory-related and 20% attributable to postprocedure hospital stay. Patient factors, including severity of illness and extent of coronary disease, and hospital characteristics, including for profit status and geographic region, identified significant variations in cost. Intensive care was used for 53% of non-STEMI and increased costs by $3282. Postdischarge 1-year costs averaged $8037, and 48% of patients were rehospitalized (half within 2 months and 57% with a cardiovascular diagnosis). Conclusions While much of the cost of patients with acute MI treated with percutaneous coronary intervention is probably not modifiable by the care team, cost reductions are still possible through quality-preserving practice efficiencies, such as need-based use rather than routine use of intensive care unit for patients with stable non-STEMI. Clinical Trial Registration URL: https://www.clinicaltrials.gov . Unique identifier: NCT00097591.

Economic and Quality-of-Life Outcomes of Natriuretic Peptide-Guided Therapy for Heart Failure.

BACKGROUND: The GUIDE-IT (GUIDing Evidence Based Therapy Using Biomarker Intensified Treatment in Heart Failure) trial prospectively compared the efficacy of an N-terminal pro-B-type natriuretic peptide (NT-proBNP)-guided heart failure treatment strategy (target NT-proBNP level <1,000 pg/ml) with optimal medical therapy alone in high-risk patients with heart failure and reduced ejection fraction. When the study was stopped for futility, 894 patients had been enrolled. OBJECTIVES: The purpose of this study was to assess treatment-related quality-of-life (QOL) and economic outcomes in the GUIDE-IT trial. METHODS: The authors prospectively collected a battery of QOL instruments at baseline and 3, 6, 12, and 24 months post-randomization (collection rates 90% to 99% of those eligible). The principal pre-specified QOL measures were the Kansas City Cardiomyopathy Questionnaire (KCCQ) Overall Summary Score and the Duke Activity Status Index (DASI). Cost data were collected for 735 (97%) U.S. RESULTS: Baseline variables were well balanced in the 446 patients randomized to the NT-proBNP-guided therapy and 448 to usual care. Both the KCCQ and the DASI improved over the first 6 months, but no evidence was found for a strategy-related difference (mean difference [biomarker-guided - usual care] at 24 months of follow-up 2.0 for DASI [95% confidence interval (CI): -1.3 to 5.3] and 1.1 for KCCQ [95% CI: -3.7 to 5.9]). Total winsorized costs averaged $5,919 higher in the biomarker-guided strategy (95% CI: -$1,795, +$13,602) over 15-month median follow-up. CONCLUSIONS: A strategy of NT-proBNP-guided HF therapy had higher total costs and was not more effective than usual care in improving QOL outcomes in patients with heart failure and a reduced ejection fraction. (Guiding Evidence Based Therapy Using Biomarker Intensified Treatment [GUIDE-IT]; NCT01685840).

Economic Outcomes With Anatomical Versus Functional Diagnostic Testing for Coronary Artery Disease.

BACKGROUND: PROMISE (PROspective Multicenter Imaging Study for Evaluation of Chest Pain) found that initial use of at least 64-slice multidetector computed tomography angiography (CTA) versus functional diagnostic testing strategies did not improve clinical outcomes in stable symptomatic patients with suspected coronary artery disease (CAD) requiring noninvasive testing. OBJECTIVE: To conduct an economic analysis for PROMISE (a major secondary aim of the study). DESIGN: Prospective economic study from the U.S. perspective. Comparisons were made according to the intention-to-treat principle, and CIs were calculated using bootstrap methods. (ClinicalTrials.gov: NCT01174550). SETTING: 190 U.S. centers. PATIENTS: 9649 U.S. patients enrolled in PROMISE between July 2010 and September 2013. Median follow-up was 25 months. MEASUREMENTS: Technical costs of the initial (outpatient) testing strategy were estimated from Premier Research Database data. Hospital-based costs were estimated using hospital bills and Medicare cost-charge ratios. Physician fees were taken from the Medicare Physician Fee Schedule. Costs were expressed in 2014 U.S. dollars, discounted at 3% annually, and estimated out to 3 years using inverse probability weighting methods. RESULTS: The mean initial testing costs were $174 for exercise electrocardiography; $404 for CTA; $501 to $514 for pharmacologic and exercise stress echocardiography, respectively; and $946 to $1132 for exercise and pharmacologic stress nuclear testing, respectively. Mean costs at 90 days were $2494 for the CTA strategy versus $2240 for the functional strategy (mean difference, $254 [95% CI, -$634 to $906]). The difference was associated with more revascularizations and catheterizations (4.25 per 100 patients) with CTA use. After 90 days, the mean cost difference between the groups out to 3 years remained small. LIMITATION: Cost weights for test strategies were obtained from sources outside PROMISE. CONCLUSION: Computed tomography angiography and functional diagnostic testing strategies in patients with suspected CAD have similar costs through 3 years of follow-up. PRIMARY FUNDING SOURCE: National Heart, Lung, and Blood Institute.

How Reliable are Patient-Reported Rehospitalizations? Implications for the Design of Future Practical Clinical Studies.

BACKGROUND: Longitudinal clinical investigations often rely on patient reports to screen for postdischarge adverse outcomes events, yet few studies have examined the accuracy of such patient reports. METHODS AND RESULTS: Patients with acute myocardial infarction (MI) in the TRANSLATE-ACS study were asked during structured interviews at 6 weeks, 6 months, and 12 months postdischarge to report any rehospitalizations. The accuracy of patient-reported rehospitalizations within 1 year of postdischarge was determined using claims-based medical bill validation as the reference standard. The cumulative incidence of rehospitalizations was compared when identified by patient report versus medical bills. Patients were categorized by the accuracy in reporting events (accurate, under-, or over- reporters) and characteristics were compared between groups. Among 10 643 MI patients, 4565 (43%) reported 7734 rehospitalizations. The sensitivity and positive predictive value of patient-reported rehospitalizations were low at 67% and 59%, respectively. A higher cumulative incidence of rehospitalization was observed when identified by patient report versus medical bills (43% vs 37%; P<0.001). Overall, 18% of patients over-reported and 10% under-reported the number of hospitalizations. Compared with accurate reporters, under-reporters were more likely to be older, female, African American, unemployed, or a non-high-school graduate, and had greater prevalence of clinical comorbidities such as diabetes and past cardiovascular disease. CONCLUSIONS: The accuracy of patient-reported rehospitalizations was low with patients both under- and over-reporting events. Longitudinal clinical research studies need additional mechanisms beyond patient report to accurately identify rehospitalization events. CLINICAL TRIAL REGISTRATION: URL: https://clinicaltrials.gov. Unique identifier: NCT01088503.

Quality of life and economic outcomes with surgical ventricular reconstruction in ischemic heart failure: results from the Surgical Treatment for Ischemic Heart Failure trial.

BACKGROUND: Surgical ventricular reconstruction (SVR) is used in conjunction with coronary artery bypass graft surgery (CABG) to improve left ventricular function and clinical outcomes in selected patients with ischemic heart failure. The impact of SVR on quality of life (QOL) and medical costs is unknown. METHODS: We compared CABG plus SVR with CABG alone in 1,000 patients with ischemic heart failure, an anterior wall scar, and a left ventricular ejection fraction or=92% complete. Cost data were collected on 196 (98%) of 200 patients enrolled in the United States. RESULTS: Heart-failure-related QOL outcomes did not differ between the 2 treatment strategies out to 3 years (median Kansas City Cardiomyopathy Questionnaire scores for CABG alone and CABG plus SVR, respectively: baseline 53 versus 54, P = .53; 3 years 85 versus 84, P = .89). There were no treatment-related differences in other QOL measures. In the US patients, total index hospitalization costs averaged over $14,500 higher for CABG plus SVR (P = .004) due primarily to 4.2 extra postoperative, high-intensity care days in the hospital. CONCLUSIONS: Addition of SVR to CABG in patients with ischemic heart failure did not improve QOL but significantly increased health care costs.

Long-term economic outcomes associated with intensive versus moderate lipid-lowering therapy in coronary artery disease: results from the Treating to New Targets (TNT) Trial.

BACKGROUND: In 10,001 patients with stable coronary artery disease (CAD) enrolled in the Treating to New Targets (TNT) trial, 80 mg/d of atorvastatin (high-dose regimen) reduced the composite primary end point of death from CAD, nonfatal myocardial infarction, resuscitation from cardiac arrest, or stroke by 22% relative to 10 mg/d (low-dose regimen). METHODS: We performed an economic analysis of this trial from the US perspective using hospital bills and Medicare physician fees to estimate costs for cardiovascular hospitalizations in all US patients (n = 5,308). Atorvastatin costs were assigned using a discounted average wholesale price. Cost-effectiveness was calculated as the within-trial incremental cost required to prevent one primary end point event with high-dose atorvastatin. RESULTS: During a mean 4.9-year follow-up, the high-dose arm had fewer potential end point cardiovascular hospitalizations (35% vs 41%, P < .001) and revascularization procedures (16% vs 22%, P < .001). The high-dose regimen was $1 per day more expensive. At the end of 5 years, cumulative incremental cost for the high-dose arm was $252 (95% CI-$722 to +$1,276). With an absolute reduction in the primary end point of 2.8 per 100 treated with the high-dose regimen, the cost to prevent one additional primary end point event was $8,964. CONCLUSION: High-dose atorvastatin treatment of 5 years had only a small net incremental cost because of reduced complications and procedures. The cost to prevent one additional primary end point event with high-dose therapy was similar to that for drug-eluting stents versus bare metal stents in stable CAD and for early invasive versus early conservative therapy in acute coronary syndromes.

Development and validation of a simple model to predict severe coronary artery disease after myocardial infarction: potential impact on cardiac catheterization use in the United States and Canada.

BACKGROUND: Improved patient selection may optimize the efficiency of cardiac catheterization in both high- and low-rate regions. The purpose of this study was to develop and validate a clinical model for predicting high-risk coronary artery disease (CAD) after myocardial infarction (MI) and to examine the model's potential impact on the use rate of both US and Canadian catheterization practices. METHODS AND RESULTS: By the use of baseline clinical variables from 1122 patients in the angiographic substudy of the Global Use of Strategies to Open Occluded Arteries in Acute Coronary Syndromes (GUSTO-1) trial, we developed a model that was predictive of severe CAD (left main or triple-vessel disease). The final model, which included prior MI, age, sex, hyperlipidemia, and decreased left ventricular ejection fraction (C-index = 0.70), was externally validated in 781 patients in the GUSTO IIb trial. Although the probability of severe CAD predicted 5-year survival, the frequency of catheterization in both Canada and the United States bore no relationship to severe CAD risk in the GUSTO-1 trial. By use of the model, we estimated that as much as 15% of US catheterizations from both GUSTO-1 and GUSTO IIb might have been avoided, without significantly compromising the number of patients with severe CAD who were identified (sensitivity = 0.94). By applying the model to Canadian practices, an additional 30 cases of severe CAD might have been identified per every 1000 catheterizations performed, without increasing the catheterization rate. CONCLUSIONS: The likelihood of severe CAD after ST-elevation MI may be predicted from simple baseline clinical variables. The use of a severe CAD predictive model to guide patient selection might enhance the cost-effectiveness of both aggressive and conservative catheterization practices.