Comparing the cost-effectiveness of four novel risk markers for screening asymptomatic individuals to prevent cardiovascular disease (CVD) in the US population.

BACKGROUND: High sensitivity CRP (hsCRP), coronary artery calcification on CT (CT calcium), carotid artery intima media thickness on ultrasound (cIMT) and ankle-brachial index (ABI) improve prediction of cardiovascular disease (CVD) risk, but the benefit of screening with these novel risk markers in the U.S. population is unclear. METHODS AND RESULTS: A microsimulation model evaluating lifelong cost-effectiveness for individuals aged 40-85 at intermediate risk of CVD, using 2003-2004 NHANES-III (N=3736), Framingham Heart Study, U.S. Vital Statistics, meta-analyses of independent predictive effects of the four novel risk markers and treatment effects was constructed. Using both an intention-to-treat (assumes adherence <100% and incorporates disutility from taking daily medications) and an as-treated (100% adherence and no disutility) analysis, quality adjusted life years (QALYs), lifetime costs (2014 US $), and incremental cost-effectiveness ratios (ICER in $/QALY gained) of screening with hsCRP, CT coronary calcium, cIMT and ABI were established compared with current practice, full adherence to current guidelines, and ubiquitous statin therapy. In the intention-to-treat analysis in men, screening with CT calcium was cost effective ($32,900/QALY) compared with current practice. In women, screening with hsCRP was cost effective ($32,467/QALY). In the as-treated analysis, statin therapy was both more effective and less costly than all other strategies for both men and women. CONCLUSIONS: When a substantial disutility from taking daily medication is assumed, screening men with CT coronary calcium is likely to be cost-effective whereas screening with hsCRP has value in women. The individual perceived disutility for taking daily medication should play a key role in the decision.

The potential cost-effectiveness of the Diamondback 360® Coronary Orbital Atherectomy System for treating de novo, severely calcified coronary lesions: an economic modeling approach.

BACKGROUND: Patients who undergo percutaneous coronary intervention (PCI) for severely calcified coronary lesions have long been known to have worse clinical and economic outcomes than patients with no or mildly calcified lesions. We sought to assess the likely cost-effectiveness of using the Diamondback 360(®) Orbital Atherectomy System (OAS) in the treatment of de novo, severely calcified lesions from a health-system perspective. METHODS AND RESULTS: In the absence of a head-to-head trial and long-term follow up, cost-effectiveness was based on a modeled synthesis of clinical and economic data. A cost-effectiveness model was used to project the likely economic impact. To estimate the net cost impact, the cost of using the OAS technology in elderly (⩾ 65 years) Medicare patients with de novo severely calcified lesions was compared with cost offsets. Elderly OAS patients from the ORBIT II trial (Evaluate the Safety and Efficacy of OAS in Treating Severely Calcified Coronary Lesions) [ClinicalTrials.gov identifier: NCT01092426] were indirectly compared with similar patients using observational data. For the index procedure, the comparison was with Medicare data, and for both revascularization and cardiac death in the following year, the comparison was with a pooled analysis of the Harmonizing Outcomes with Revascularization and Stents in Acute Myocardial Infarction (HORIZONS-AMI)/Acute Catheterization and Urgent Intervention Triage Strategy (ACUITY) trials. After adjusting for differences in age, gender, and comorbidities, the ORBIT II mean index procedure costs were 17% (p < 0.001) lower, approximately US$2700. Estimated mean revascularization costs were lower by US$1240 in the base case. These cost offsets in the first year, on average, fully cover the cost of the device with an additional 1.2% cost savings. Even in the low-value scenario, the use of the OAS is cost-effective with a cost per life-year gained of US$11,895. CONCLUSIONS: Based on economic modeling, the recently approved coronary OAS device is projected to be highly cost-effective for patients who undergo PCI for severely calcified lesions.

Outcomes after coronary artery calcium and other cardiovascular biomarker testing among asymptomatic medicare beneficiaries.

BACKGROUND: Biomarkers improve cardiovascular disease (CVD) risk prediction, but their comparative effectiveness in clinical practice is not known. We sought to compare the use, spending, and clinical outcomes in asymptomatic Medicare beneficiaries evaluated for CVD with coronary artery calcium (CAC) or other cardiovascular risk markers. METHODS AND RESULTS: We used a 20% sample of 2005 to 2011 Medicare claims to identify fee-for-service beneficiaries aged ≥65.5 years with no CVD claims in the previous 6 months. We matched patients with CAC with patients who received high-sensitivity C-reactive protein (hs-CRP; n=8358) or lipid screening (n=6250) using propensity-score methods. CAC was associated with increased noninvasive cardiac testing within 180 days (hazard ratio, 2.22, 95% confidence interval, 1.68-2.93, P<0.001, versus hs-CRP; hazard ratio, 4.30, 95% confidence interval, 3.04-6.06, P<0.001, versus lipid screening) and increased coronary angiography and revascularization. During 3-year follow-up, CAC was associated with higher CVD-related spending ($6525 versus $4432 for hs-CRP, P<0.001; and $6500 versus $3073 for lipid screening, P<0.001) and fewer CVD-related events when compared with hs-CRP (hazard ratio, 0.74, 95% confidence interval, 0.58-0.94, P=0.017) but not compared with lipid screening (hazard ratio, 0.84, 95% confidence interval, 0.64-1.11, P=0.23). CONCLUSIONS: CAC testing among asymptomatic Medicare beneficiaries was associated with increased use of cardiac tests and procedures, higher spending, and slightly improved clinical outcomes when compared with hs-CRP testing.

Diagnosis of breast lesions: fine-needle aspiration cytology or core needle biopsy? A review.

Diagnosis of breast lesions is routinely performed by the triple assessment of a specialised surgeon, radiologist and pathologist. In this setting, fine-needle aspiration cytology (FNAC) and core needle biopsy (CNB) are the current methods of choice for pathological diagnosis, both with their specific advantages and limitations. Evidence-based literature discussing which of both modalities is preferable in breast lesion diagnosis is sparse and there is no consensus among different specialised breast cancer centres. This study reviews FNAC and CNB for diagnosing breast lesions, comparing methodological issues, diagnostic performance indices, possibilities for additional prognostic and predictive tests and cost effectiveness. Overall, CNB achieved better sensitivity and specificity especially in those lesions that were not definitively benign or malignant, non-palpable and/or calcified lesions. Although FNAC is easier to perform, interpretation requires vast experience and even then, it is more often inconclusive requiring additional CNB. The authors conclude that overall CNB is to be preferred as a diagnostic method.

Long-period pancreatic stenting for painful chronic calcified pancreatitis required higher medical costs and frequent hospitalizations compared with surgery.

OBJECTIVES: The aim of this study was to compare the benefits between endoscopic drainage and surgical drainage of the pancreatic duct for patients with chronic calcified pancreatitis. METHODS: A total of 68 patients were classified into endoscopic (n = 34) or surgical (n = 34) treatment groups. Patients receiving endoscopic treatment were further divided into 2 subgroups: a short-period group, patients who could discontinue serial pancreatic stenting within 1 year (n = 19); and a long-period group, patients who needed pancreatic drainage by serial endoscopic stenting for more than 1 year (n = 15). The medical records of these patients were retrospectively analyzed. RESULTS: Hospital stays, frequency of hospitalizations, and medical expense were similar between the short-period endoscopic treatment group and surgery group. On the other hand, patients in the long-period endoscopic treatment group required significantly longer hospital stays, more frequent hospitalizations, and had higher medical expenses than the short-period endoscopic treatment group as well as than the surgery group. CONCLUSIONS: Patients who underwent serial endoscopic stenting for more than 1 year showed no benefit compared with surgical treatment in terms of the frequency of hospital stays and medical costs.

Coronary artery calcium to predict all-cause mortality in elderly men and women.

OBJECTIVES: We sought to study the prognostic utility of coronary artery calcium (CAC) in the elderly. BACKGROUND: The prognostic significance of CAC in the elderly is not well known. METHODS: All-cause mortality was assessed in 35,388 patients (3,570 were >or=70 years old at screening, and 50% were women) after a mean follow-up of 5.8 +/- 3 years. RESULTS: In older patients, risk factors and CAC were more prevalent. Overall survival was 97.9% at the end of follow-up. Mortality increased with each age decile with a relative hazard of 1.09 (95% confidence interval: 1.08 to 1.10, p < 0.0001), and rates were greater for men than women (hazard ratio: 1.53; 95% confidence interval: 1.32 to 1.77, p < 0.0001). Increasing CAC scores were associated with decreasing survival across all age deciles (p < 0.0001). Survival for a <40-year and >or=80-year-old man with a CAC score >or=400 was 88% and 19% (95% and 44% for a woman, p < 0.0001), respectively. Among the 20,562 patients with no CAC, annual mortality rates ranged from 0.3% to 2.2% for patients age 40 to 49 years or >or=70 years (p < 0.0001). The use of CAC allowed us to reclassify more than 40% of the patients >or=70 years old more often by excluding risk (i.e., CAC <400) in those with >3 risk factors. CONCLUSIONS: Despite their limited life expectancy, the use of CAC discriminates mortality risk in the elderly. Furthermore, the use of CAC allows physicians to reclassify risk in the elderly.

Cost effectiveness of coronary angiography and calcium scoring using CT and stress MRI for diagnosis of coronary artery disease.

We compared the cost effectiveness of recent approaches [coronary angiography and calcium scoring using computed tomography (CT) and stress magnetic resonance imaging (MRI)] to the diagnosis of coronary artery disease (CAD) with those of the traditional diagnostic modalities [conventional angiography (CATH), exercise ECG, and stress echocardiography] using a decision tree model. For patients with a 10% to 50% pretest likelihood of coronary artery disease, non-invasive coronary angiography using CT was the most cost effective approach, with costs per correctly identified CAD patient of euro4,435 (10% likelihood) to euro1,469 (50% likelihood). Only for a pretest likelihood of 30% to 40% was calcium scoring using CT more cost effective than any of the traditional diagnostic modalities, while MRI was not cost effective for any pretest likelihood. At a pretest likelihood of 60%, CT coronary angiography and CATH were equally effective, while CATH was most cost effective for a pretest likelihood of at least 70%. In conclusion, up to a pretest likelihood for coronary artery disease of 50%, CT coronary angiography is the most cost-effective procedure, being superior to the other new modalities and the most commonly used traditional diagnostic modalities. With a very high likelihood for disease (above 60%), CATH is the most effective procedure from the perspective of society.

Treatment for painful calcified chronic pancreatitis: extracorporeal shock wave lithotripsy versus endoscopic treatment: a randomised controlled trial.

BACKGROUND: In chronic pancreatitis, obstruction of the main pancreatic duct (MPD) may contribute to the pathogenesis of pain. Pilot studies suggest that extracorporeal shock wave lithotripsy (ESWL) alone relieves pain in calcified chronic pancreatitis. AIM: To compare ESWL alone with ESWL and endoscopic drainage of the MPD for treatment of pain in chronic pancreatitis. SUBJECTS: Patients with uncomplicated painful chronic pancreatitis and calcifications obstructing the MPD. METHODS: 55 patients were randomised to ESWL alone (n = 26) or ESWL combined with endoscopy (n = 29). RESULTS: 2 years after trial intervention, 10 (38%) and 13 (45%) patients of the ESWL alone and ESWL combined with endoscopy group, respectively, had presented pain relapse (primary outcome) (OR 0.77; 95% CI 0.23 to 2.57). In both groups, a similar decrease was seen after treatment in the MPD diameter (mean decrease 1.7 mm; 95% CI 0.9 to 2.6; p<0.001), and in the number of pain episodes/year (mean decrease, 3.7; 95% CI 2.6 to 4.9; p<0.001). Treatment costs per patient were three times higher in the ESWL combined with endoscopy group compared with the ESWL alone group (p = 0.001). The median delay between the onset of chronic pancreatitis and persistent pain relief for both groups was 1.1 year (95% CI 0.7 to 1.6), as compared with 4 years (95% CI 3 to 4) for the natural history of chronic pancreatitis in a reference cohort (p<0.001). CONCLUSIONS: ESWL is a safe and effective preferred treatment for selected patients with painful calcified chronic pancreatitis. Combining systematic endoscopy with ESWL adds to the cost of patient care, without improving the outcome of pancreatic pain.

Health and economic consequences of sevelamer use for hyperphosphatemia in patients on hemodialysis.

OBJECTIVES: The safety and efficacy of sevelamer hydrochloride in binding phosphate in patients with end-stage renal disease and its ability to attenuate the progression of cardiac calcification have been well documented but not the longer-term health and economic implications. Thus, a model of the predicted long-term consequences of sevelamer compared with calcium-based binders (acetate and carbonate) was developed. METHODS: Long-term cardiovascular implications of 1 year of treatment with phosphate binders in patients on hemodialysis are estimated based on the patient's demographics, comorbidities, and physiologic and renal parameters. The initial calcification score and expected changes over 1 year are derived using regression equations developed from the Treat-to-Goal study and translated to cardiovascular disease risk based on equations developed from a long-term cohort study. In this article, the implications of cardiovascular disease for life expectancy and medical costs are accounted for from a US payer perspective. RESULTS: The cardioprotective effect of sevelamer over 1 year is estimated to result in a 12% reduction in cardiovascular events compared with calcium acetate. In a population of 100 patients, the savings of 205,600 dollars accrued due to avoiding nine cardiovascular events with sevelamer, largely offset the increased binder costs, leading to a favorable cost-effectiveness ratio of about 2200 dollars per (discounted) life-year gained. CONCLUSIONS: Although both binders provide equivalent phosphate binding capacity, the results indicate that the advantage of 1 year of treatment with sevelamer in attenuating the progression of calcification has important clinical and economic consequences, suggesting that this provides good value for money.

Cost effectiveness of screening for cardiovascular disease with measures of coronary calcium.

Cardiovascular disease is the leading cause of morbidity and mortality with annual costs of care exceeding 300 billion US dollars. Although screening tools are advocated for many cancers, the use of subclinical disease tests for cardiovascular disease are considered controversial. Health care payers and many governmental agencies apply cost-effectiveness analysis for the evaluation of new technology being considered for routine application in the US and Europe. Cost-effectiveness analysis by definition provides a comparative analysis of clinical and economic outcome data when evaluating new technology in relation to existing modalities. The current report provides a description of the framework upon methods applied in cost-effectiveness analysis as well as available data on the subject of cardiovascular screening, most notably using the evaluation of coronary calcium screening with electron beam tomography. The current report will also present several decision analytic models on the cost of atherosclerotic imaging including the evaluation of serial monitoring for disease progression and the development of cost-effectiveness models employing intermediate outcomes. Based on this review, there is an unfolding body of evidence that explores both the clinical and economic consequences of screening for atherosclerotic diseases. Although further evidence is required from prospectively designed randomized controlled trials, it appears that the current evidence from small series and decision analytic models supports cardiovascular screening of asymptomatic individuals and that the current results reveal enhanced cost effectiveness when compared with the routine evaluation using a Framingham risk assessment.

[Economic aspects of using electron beam computerized tomography]. / Okonomische Aspekte bei der Anwendung der Elektronenstrahlcomputertomographie.

Electron beam computed tomography (EBCT) allows visualization and quantification of calcium in the coronary arteries. This has been demonstrated to correlate well with the overall plaque burden in the coronary arteries. EBCT is, therefore, well suited for the detection of early stages of coronary atherosclerosis. Especially in asymptomatic patients with several risk factors, staging coronary artery disease by coronary calcium, scanning may allow prognostic assessment and guide preventive and therapeutic interventions. To date, only scant data are available regarding the cost effectiveness and the economic impact of this imaging technique. In this manuscript we compare various methods for the diagnosis of coronary artery disease using a theoretical model and review the results of a prospective trial in our emergency room of coronary calcium scanning in patients with acute chest pain. Using Framingham data and prognostic data from long-term follow-up, we discuss the impact of coronary calcification scanning on primary preventive measures and its economical consequences. EBCT is a promising technique which has created a lot of attention due to its ease of application. It is currently undergoing critical appraisal in the medical literature. Further randomized prospective trials are needed (and underway, i.e., MESA, EDIC, CARDIA II) to better define its value and limitations in the clinical arena.

Cost effectiveness of coronary calcification scanning using electron beam tomography in intermediate and high risk asymptomatic individuals.

Pharmaceutical therapy of hyperlipidemia is clearly beneficial. In the patient without established heart disease however, conventional risk assessment is imprecise and determining which patients are at highest versus lowest risk is a common clinical conundrum. It is well established that the most powerful determinant to risk is the overall extent/severity of coronary disease. Electron beam tomography (EBT) and quantification of coronary artery calcium has been shown to provide a valid non-invasive surrogate to atherosclerotic plaque burden. Screening patients who are considered to be at traditional intermediate to high risk by first using EBT can refine the broad-based population risk to a more individual basis. Data that is based upon a model developed for application of EBT are presented, which discuss its potential as a cost effective application to guide statin therapy in intermediate and high-risk sub-groups.

Techniques and results of direct-access minimally invasive mitral valve surgery: a paradigm for the future.

OBJECTIVES: Our objective was to determine whether direct-access minimally invasive mitral valve surgery can improve recovery and cost while maintaining the efficacy of conventional surgery. METHODS: Minimally invasive mitral valve operations were performed on 106 patients, 58% male, average age 58.1 years, with good ventricular function. Ninety underwent repair of a regurgitant, myxomatous valve, and 16 underwent mitral valvuloplasty for prematurely calcified mitral stenosis. The valve was approached with standard instruments through a 5- to 8-cm right parasternal incision. Eighty-five had open femoral artery-femoral vein cannulation, but this technique has recently been replaced by direct cannulation of the aorta and percutaneous cannulation of the femoral vein for most patients. RESULTS: There were no operative deaths. The mean mitral regurgitation score (0-4) decreased from 3.7 to 0.7 after the operation. Although ischemic and bypass times were increased, postoperative recovery was accelerated. Ventilatory support time, intensive care unit stay, hospital stay, need for rehabilitation, and return to "normal activities" all improved. Hospital charges, pain medications, and blood transfusions were also reduced. New atrial fibrillation contributed significantly to increased length of stay and charges. There were no deep wound infections. Other complications included re-exploration for bleeding (n = 1), transient ischemic attacks (n = 2), stroke (n = 1), femoral artery injury (n = 5), pseudoaneurysm (n = 2), and antegrade dissection of the ascending aorta (n = 1). Two patients died and 1 required reoperation during a mean follow-up of 8.8 months. CONCLUSIONS: Direct-access minimally invasive mitral valve surgery can accelerate recovery, decrease charges, and decrease pain, while maintaining overall surgical efficacy. It has become our standard approach for isolated primary mitral valve operations.

[Electron beam tomography in cost effective diagnosis of coronary heart disease]. / Die Elektronenstrahltomographie in der kosteneffizienten Diagnostik der koronaren Herzkrankheit.

BACKGROUND: Electron beam CT (EBCT) can acquire rapid, multiple thin-section tomograms of the beating heart in synchrony with the electrocardiogram and quantity coronary calcification without intravenous contrast. Coronary calcification is an active process exclusively associated with atherosclerotic plaque formation and regulated in a manner similar to the calcification of bone. Clinical studies have demonstrated that EBCT coronary calcification (1) follows a pattern similar to the epidemiology of coronary artery disease (CAD), (2) has a high sensitivity (90-95%) for coronary plaque and significant angiographic coronary stenoses, and (3) has the potential to assess the prognosis of patients with coronary atherosclerotic disease. Coronary calcium area or "score" correlates best with overall plaque burden within the coronary system. However, coronary calcium is of limited value in distinguishing coronary stenosis on a segment-by-segment basis. EBCT AND CAD: Due to spiraling health care costs, there is a need for cost-efficient strategies in the diagnosis and stratification of patients with known or suspected CAD. There are two major patient groups in which EBCT calcium scanning has a potential for cost-efficient application: (1) in asymptomatic, high-risk patients, identification of significant plaque burden may direct judicious use of long-term drug therapy or further investigation to those individuals most likely to benefit from an aggressive risk factor modification and medical program; (2) in patients with chest pain syndromes but no prior CAD, EBCT calcium scanning compares favorably with conventional diagnostic methods. In particular, using receiver operating characteristic analysis, the sensitivity and specificity of an EBCT calcium score of 80 in detecting obstructive CAD are both about 85%. Using a theoretical model, EBCT calcium scanning was found to be the most cost-effective approach to diagnosis in populations with a low-to-moderate likelihood of obstructive CAD when compared with treadmill exercise, stress thallium, and stress echocardiography. CONCLUSIONS: EBCT calcium scanning is not a substitute for coronary angiography, but it has clear advantages over other more traditional diagnostic methods for CAD. In particular, it can be performed conveniently and inexpensively in most patients. Additionally, the site and extent of calcification are intimately related to the atherosclerotic plaque burden. The analyses presented suggest that it may also provide a cost-effective clinical alternative in specific subsets of the population.