Determinants of imminent fracture risk in postmenopausal women with osteoporosis.

In elderly women with osteoporosis, prior fracture, low BMD, impaired physical functioning, poorer general health, and recent falls were all direct predictors of imminent (in next year) fracture risk. Prior fracture, older age, worse health, impaired cognitive functioning, and recent falls indirectly increased imminent risk by reducing physical functioning/general health. INTRODUCTION: This study was designed to examine determinants of imminent risk of osteoporotic fracture (i.e., next 1-2 years) in postmenopausal women. METHODS: This retrospective cohort study used data from Caucasian women age 65 or older with osteoporosis who participated in the observational Study of Osteoporotic Fractures (SOF). We examined potential direct and indirect predictors of hip and nonvertebral fractures in 1-year follow-up intervals including anthropometric measures, bone mineral density (T-score), fracture since age 50, physical function, cognition, medical conditions, recent (past year) falls, and lifestyle factors. Clinically related variables were grouped into constructs via factor analysis. These constructs and selected individual variables were incorporated into a theoretical structural equation model to evaluate factors that influence imminent risk. RESULTS: Among 2261 patients, 19.4% had a nonvertebral fracture and 5.5% had a hip fracture within 1 year of a study visit between 1992 and 2008. Prior fracture, lower T-scores, lower physical functioning, and recent falls all directly increased 1-year risk of nonvertebral fracture. For both nonvertebral and hip fractures, prior fracture and recent falls influenced risk indirectly through general health, while cognition influenced risk via physical functioning. Age influenced both physical functioning and general health. CONCLUSIONS: Several established risk factors for 10-year fracture risk also played a role in predicting imminent risk of fracture (e.g., T-scores, prior fracture), as did falls, cognition, physical functioning, and general health. Fracture risk assessments should also consider falls and fall risk factors as well as established bone-related risk factors in assessing imminent fracture risk.

Predictors of near-term fracture in osteoporotic women aged ≥65 years, based on data from the study of osteoporotic fractures.

Using data from the Study of Osteoporotic Fractures (SOF), several clinical characteristics predictive of near-term (1-year) risk of hip and non-vertebral fracture among elderly osteoporotic women were identified, and a subset of those for hip fracture was incorporated into a risk assessment tool. Additional research is needed to validate study findings. INTRODUCTION: While several risk factors are known to contribute to long-term fracture risk in women with osteoporosis, factors predicting fracture risk over a shorter time horizon, such as over a 1-year period, are less well-established. METHODS: We utilized a repeated-observations design and data from the Study of Osteoporotic Fractures to identify factors contributing to near-term risk of hip fracture and any non-vertebral fracture, respectively, among osteoporotic women aged ≥65 years. Potential predictors of hip fracture and any non-vertebral fracture over the 1-year period subsequent to each qualifying SOF exam were examined using multivariable frailty models. Because the discriminative ability of the hip fracture model was acceptable, a corresponding risk-prediction tool was also developed. RESULTS: Study population included 2499 women with osteoporosis, who contributed 6811 observations. Incidence of fracture in the 1-year period subsequent to each exam was 2.2% for hip fracture and 6.6% for any non-vertebral fracture. Independent predictors of hip fracture included low total hip T-score, prior fracture, and risk factors for falls (multivariable model c-statistic = 0.71 (95% CI 0.67-0.76)). Independent predictors of any non-vertebral fracture included age, total hip T-score, prior falls, prior fracture, walking speed, Parkinson's disease or stroke, and smoking (multivariable model c-statistic = 0.62 (0.59-0.65)). CONCLUSIONS: Several clinical characteristics predictive of hip and non-vertebral fracture within a 1-year follow-up period among elderly women with osteoporosis were identified, and a subset of those for hip fracture was incorporated into a risk assessment tool. Assessment of these risk factors may help guide osteoporosis treatment choices by identifying patients in whom there is urgency to treat. Additional research is needed to validate the findings of this study and the accuracy of the risk assessment tool.

Adherence with bisphosphonate therapy and change in bone mineral density among women with osteoporosis or osteopenia in clinical practice.

UNLABELLED: In clinical practice, adherence with bisphosphonate therapy varies greatly among women with osteoporosis or osteopenia. Our study suggests that better adherence with bisphosphonates confers tangible benefits in terms of graded increases in bone mineral density. Interventions to improve drug adherence should be an important component of disease management. INTRODUCTION: In clinical trials, bisphosphonates have been found to increase bone mineral density (BMD) in women with osteoporosis or osteopenia. In clinical practice, where drug adherence is more variable, change in BMD with bisphosphonate therapy-overall and by level of adherence-is largely unknown. METHODS: A retrospective cohort study was conducted at Henry Ford Health System (Detroit, MI, USA). Study subjects were women who had low BMD at the left total hip (T-score<-1.0), began oral bisphosphonate therapy, and had ≥1 BMD measurements at the left total hip≥6 months following treatment initiation. Change in BMD was calculated between the most recent pretreatment scan and the first follow-up scan. Adherence (i.e., medication possession ratio (MPR)) was measured from therapy initiation to the first follow-up scan. RESULTS: Among 644 subjects, mean age was 66 years, pretreatment BMD was 0.73 g/cm2, and pretreatment T-score was -1.8. Over a mean follow-up of 27.1 months, mean MPR was 0.57 (95% CI, 0.54 and 0.59), and mean percentage change in BMD was 1.5% (1.1 and 1.9%). Within the MPR strata (five consecutive equi-intervals, from low (0-0.19) to high (0.80-1.0)), mean change in BMD was -0.8% (-1.6 and 0.1%), 0.7% (-0.3 and 1.7%), 2.1% (1.1 and 3.0%), 2.1% (1.4 and 2.9%), and 2.9% (2.3 and 3.5%), respectively. In adjusted analyses, percentage change in BMD was higher (by 1.4-3.4%, p<0.05 for all) in the highest four MPR intervals, respectively, versus MPR 0-0.19. CONCLUSIONS: Among women with osteoporosis or osteopenia in clinical practice, better adherence with bisphosphonates appears to confer tangible benefits in terms of increases in BMD.

[Generalized anxiety disorder in primary care. Patterns of healthcare utilization in Germany]. / Generalisierte Angststörung in der primärärztlichen Versorgung. Eine Analyse administrativ-epidemiologischer Daten zu Inanspruchnahme und Versorgungsmerkmalen.

BACKGROUND: Generalized Anxiety Disorder (GAD) has been described in community studies as a frequent and costly high utilizer group in the primary care sector. Administrative data supporting this observation are lacking so far. METHODS: This paper reports utilization and prescription data of a nationally representative sample of over 900 primary care physicians, over 75 million prescriptions and 12-month utilization and prescription patterns of n = 3,340 GAD patients.These are compared to a matched control group without GAD, and without any anxiety or depressive disorder (n = 3,340). RESULTS: GAD patients in comparison to the matched controls revealed: (1) 2-fold increased primary care, (2) almost 3-fold specialist referrals, (3) almost 2-fold increased overall prescription rates, and (4) 3.5-fold increased sick certificates. However, only 58.3% of GAD patients were treated with any psychotropic medication. DISCUSSION: The data of this administrative-epidemiological cohort study support strongly the view that GAD ranks among the most costly high utilizer patient group in primary care in Germany. However, they are rarely treated according to evidence-based guidelines. The paper discusses these findings by suggesting that comorbid conditions might be a barrier for primary care physicians to initiate existing, more appropriate state of the art treatments.

Treatment of new-onset ulcerative colitis and ulcerative proctitis: a retrospective study.

BACKGROUND: Although guidelines recommend use of oral 5-aminosalicylates (5-ASAs) as first-line therapy in patients with mild to moderate ulcerative colitis (UC) and ulcerative proctitis (UP) and steroids with or without 5-ASAs in those more severely ill, little is known about how UC and UP are actually treated. AIM: To document treatment of new-onset UC and UP in routine clinical practice. METHODS: Using a large US health insurance database, we identified all persons with new-onset UC or UP between 1 January 2005 and 31 December 2007, based on: (i) initial receipt of an oral 5-ASA, mesalazine (mesalamine) suppository, 5-ASA enema, steroid, antimetabolite, budesonide or TNF inhibitor; (ii) sigmoidoscopy/colonoscopy in prior 30 days resulting in a new diagnosis of UC or UP and (iii) no prior encounters for Crohn's disease. We examined patterns of pharmacotherapy over 1 year. RESULTS: We identified 1516 UC patients and 636 UP patients who met study entry criteria. In UC, initial therapies most frequently used were oral 5-ASAs (53% of patients), oral 5-ASAs and systemic steroids (12%), systemic steroids (8%) and mesalazine suppositories (6%); in UP, mesalazine suppositories (42%) and oral 5-ASAs (19%) were most often used, followed by combination therapy (14%), mesalazine enema (11%) and rectal steroids (10%). Few patients received maintenance therapy, and there was limited use of antimetabolites and biological agents. CONCLUSIONS: Oral 5-ASAs and systemic steroids are the mainstay of treatment in patients with new-onset ulcerative colitis; in those with new-onset ulcerative proctitis, it is mesalazine suppositories. Care of these patients appears consistent with treatment guidelines.

Cost-effectiveness of abatacept in patients with moderately to severely active rheumatoid arthritis and inadequate response to methotrexate.

OBJECTIVE: To assess cost-effectiveness of abatacept in patients with moderately to severely active RA and inadequate response to MTX. METHODS: We developed a simulation model to depict progression of disability [in terms of the HAQ Disability Index (HAQ-DI)] in women aged 55-64 yrs with moderately to severely active RA and inadequate response to MTX. At model entry, patients were assumed to receive either only MTX or MTX plus abatacept. Patients were then tracked from model entry until death. Future health-state utilities and medical-care costs (except study therapy) were estimated based on predicted values of the HAQ-DI. The model was estimated using data from a Phase III clinical trial of abatacept plus various secondary sources. Cost-effectiveness was expressed in terms of incremental cost (2006 US$) per quality-adjusted life-year (QALY) gained over alternatively 10 yrs and a lifetime. Costs and health effects were both discounted at 3% annually. RESULTS: Over 10 yrs, abatacept would yield 1.2 additional QALYs (undiscounted) per patient (4.6 vs 3.4 for MTX) at an incremental (discounted) cost of $51,426 ($103,601 vs $52,175, respectively); over a lifetime, corresponding figures were 2.0 QALYS (6.8 vs 4.8) and $67,757 ($147,853 vs $80,096). Cost-effectiveness was [mean (95% CI)] $47,910 ($44,641, $52,136) per QALY gained over 10 yrs and $43,041 ($39,070, $46,725) per QALY gained over a lifetime. Findings were robust in sensitivity analyses. CONCLUSION: Abatacept is cost-effective by current standards of medical practice in patients with moderately to severely active RA and inadequate response to MTX.

Cost of neutropenic complications of chemotherapy.

BACKGROUND: Cost of neutropenic complications of myelosuppressive chemotherapy has been reported to be substantial. Prior research, however, has focused on initial hospitalization only and has failed to account for follow-on care. PATIENTS AND METHODS: Using a US health-care claims database, all adult cancer patients who received a course of chemotherapy were identified. For each such patient, each unique cycle of chemotherapy within the course and each occurrence of neutropenic complications within these cycles were characterized. Patients developing neutropenic complications in a given cycle (neutropenia patients), starting with the first, were matched (1:1) to those who did not develop neutropenic complications in that cycle (comparison patients), and health-care costs (i.e. expenditures) were tallied for each matched pair. RESULTS: Neutropenia patients (n = 373) and comparison patients were similar in terms of baseline characteristics. Costs of neutropenia-related care were $12,397 (95% confidence interval $10,274-$14,754) higher for neutropenia versus comparison patients [$14,407 ($12,357-$16,743) versus $2010 ($1490-$2553)]. Among neutropenia patients, mean cost of initial hospitalization for neutropenic complications was $7813 ($6537-$9379); cost of all subsequent neutropenia-related care averaged $6594 ($5217-$8272). CONCLUSIONS: Neutropenic complications of myelosuppressive chemotherapy are costly. Prior research focusing on initial hospitalization only may have underestimated the cost of these complications by as much as 40%.

Risk of chronic kidney disease in hypertensive patients with other metabolic conditions.

Using a retrospective cohort design and electronic medical records, we examined chronic kidney disease (CKD) risk over a 6-year period among hypertensive patients in relation to the presence of diabetes, hyperlipidaemia and/or high body mass index. After adjusting for age, sex, smoking status and baseline glomerular filtration rate (GFR), hypertensive patients without other metabolic risk factors had a relative risk of CKD (versus normotensive patients) of 2.0 (95% CI 1.8-2.2); hypertensive patients with other metabolic conditions had adjusted relative risks ranging from 2.4 to 2.6 for those without comorbid diabetes, and from 3.3 to 5.5 for those with comorbid diabetes. Our study thus confirms prior research demonstrating elevated CKD risk in hypertensive patients, and suggests that this risk varies substantially in relation to other metabolic conditions, especially diabetes.

Characteristics and healthcare costs of patients with fibromyalgia syndrome.

PURPOSE: To examine the characteristics and healthcare costs of fibromyalgia syndrome (FMS) patients in clinical practice. MATERIALS AND METHODS: Using a US health-insurance database, we identified all patients, aged > or = 18 years, with any healthcare encounters for FMS (ICD-9-CM diagnosis code 729.1) in each year of the 3-year period, 1 July 2002 to 30 June 2005. A comparison group was then constituted, consisting of randomly selected patients without any healthcare encounters for FMS during this 3-year period. Comparison group patients were matched to FMS patients based on age and sex. Characteristics and healthcare costs of FMS patients and comparison group patients were then examined over the 1-year period, 1 July 2004 to 30 June 2005 (the most recent year for which data were available at the time of the study). RESULTS: The study sample consisted of 33,176 FMS patients and an identical number in the comparison group. Mean age was 46 years, and 75% were women. FMS patients were more likely to have various comorbidities, including painful neuropathies (23% vs. 3% for comparison group), anxiety (5% vs. 1%), and depression (12% vs. 3%) (all p < 0.001); they also were more likely to have used pain-related pharmacotherapy (65% vs. 34% for comparison group; p < 0.001). Mean (SD) total healthcare costs over 12 months were about three times higher among FMS patients [$9573 ($20,135) vs. $3291 ($13,643); p < 0.001]; median costs were fivefold higher ($4247 vs. $822; p < 0.001). CONCLUSIONS: Patients with FMS have comparatively high levels of comorbidities and high levels of healthcare utilization and cost.

Risk of diabetes in a real-world setting among patients initiating antihypertensive therapy with valsartan or amlodipine.

In the Valsartan Antihypertensive Long-Term Use Evaluation (VALUE) trial, the risk of new-onset diabetes was reported to be 23% lower among patients initiating therapy with valsartan versus amlodipine. The objective of our study was to examine whether this finding is generalizable to 'real-world' clinical practice. A retrospective cohort design and a large US health insurance database were employed for analyses. Study subjects included all hypertensive patients, aged >or=35 years, who were free from diabetes and who initiated treatment with valsartan (n=9999) or amlodipine (n=18 698) between January 1999 and March 2005. Unadjusted absolute risks of diabetes were 21.4 (95% confidence interval (CI) 18.9-24.3) and 26.3 (95% CI 24.3-28.3) per 1000 patient-years for valsartan and amlodipine, respectively; the corresponding relative risk (RR) for valsartan was 0.82 (95% CI 0.70-0.94). Multivariate analyses - controlling for age, sex, presence of hypercholesterolemia, cardiovascular disease and kidney disease, and pretreatment medical care expenditures - yielded similar results (RR=0.79, 95% CI 0.68-0.92). Our study thus corroborates the finding from VALUE that diabetes risk is lower for patients who receive valsartan versus amlodipine, and extends this finding to a 'real-world' setting.

Compliance with osteoporosis drug therapy and risk of fracture.

INTRODUCTION: Patient compliance with osteoporosis drug therapy is often poor in clinical practice and may be associated with higher risk of fracture. METHODS: A nested case-control study was undertaken using a US health insurance claims database. The source population included all women aged >or=45 years who began drug therapy for osteoporosis. Cases consisted of those who experienced an osteoporosis-related fracture; they were matched to controls without osteoporosis-related fracture. Compliance with osteoporosis drug treatment was assessed in terms of the number of therapy-days received and medication possession ratio (MPR). Conditional logistic regression was employed to examine the relationship between compliance and fracture risk. RESULTS: A total of 453 women with osteoporosis-related fracture were identified and matched to 2,160 controls. Fracture risk was significantly lower for patients with >180 days of therapy [181-360 days: odds ratio (OR) = 0.70, 95% CI = 0.49-0.99; >360 days: OR = 0.65, 95% CI = 0.43-0.99) versus those with or=90% (OR = 0.70, 95% CI = 0.52-0.93) versus those with MPR <30%. Fracture risk decreased as compliance increased (p(trend) < 0.05). CONCLUSION: Among women initiating drug therapy for osteoporosis, better compliance is associated with reduced risk of fracture.

Compliance with drug therapy for postmenopausal osteoporosis.

INTRODUCTION: Patient compliance with pharmacotherapy for osteoporosis is typically poor in clinical practice; less frequent dosing with bisphosphonates may improve compliance. METHODS: Using data from 49 US health plans, we identified all women aged >/=45 years with osteoporosis who initiated therapy with a bisphosphonate, calcitonin, estrogen, or raloxifene. Compliance was examined alternatively in terms of incidence of adherence failure (medication days <80% of possible) and persistence failure (gap in therapy >/=90 days), and was compared across treatment groups using Kaplan-Meier methods and Cox proportional hazards models. RESULTS: The study population included 18,822 women, 48% of whom initiated weekly bisphosphonate therapy. Overall risk of adherence failure was 47% at 3 months, 70% at 1 year, and 84% at 3 years. Risk of persistence failure was 47% at 1 year, and 77% at 3 years. In multivariate analyses, risk of adherence failure was higher for calcitonin (hazard ratio=2.7 vs weekly bisphosphonate therapy, p<0.01), but comparable for all other therapies. Relative risks of persistence failure were generally similar. CONCLUSIONS: Approximately three-quarters of women who initiate osteoporosis drug therapy are non-adherent with treatment within 12 months, and almost 50% have discontinued such therapy by this time. Compliance with weekly bisphosphonate therapy is generally no better than that with osteoporosis medications requiring more frequent dosing.

Use of antiepileptics and tricyclic antidepressants in cancer patients with neuropathic pain.

Using a large US health insurance claims database, we identified all persons aged > or =18 years with > or =2 medical encounters with diagnoses of cancer and > or =2 medical encounters with diagnoses of painful neuropathies in calendar year (CY) 2000; persons with seizure disorders or depression were excluded. We then examined the use of antiepileptics (AEDs), tricyclic antidepressants (TCAs) and other pain-related pharmacotherapy among these selected persons, as proxied by pharmacy dispenses. A total of 956 persons were identified who met all entry criteria; 17% received AEDs in CY2000 and 14% received TCAs. Gabapentin was the most widely used AED (92% of all AED patients); amitriptyline was the most widely used TCA (79% of all TCA patients). Patients who received AEDs and/or TCAs were similar in age, gender and the presence of metastases to those who had not received these medications; they were more likely to have received other pain-related therapies, however, including short-acting opioids (73% vs. 53%; P < 0.01) and long-acting opioids (23% vs. 8%; P < 0.01). Use of AEDs and TCAs appears to be relatively low among cancer patients with painful neuropathies. Further research is needed to better understand reasons for this finding, as well as its potential implications for pain management in this patient population.

Effects of weight gain on medical care costs.

OBJECTIVE: To examine in middle-aged adults the effect of medical care costs of large, rapid weight gain compared to weight maintenance. DESIGN: : Retrospective cohort study for a 3-y time period. SETTING AND PARTICIPANTS: Population-based sample (N=15174) of men and women members of a large managed care organization, aged 35-65 y, with a body mass index (BMI) >25 kg/m(2) at baseline. Health-care utilization and costs were measured at baseline and over the 3-y follow-up period. RESULTS: Mean age at baseline was 49.7 y and mean BMI was 31.5 kg/m(2). During the 3-y follow-up period, 40.8% were classified as weight maintainers (+/-4 pounds), 45.3% gained 5-19 pounds, and 13.9% gained >/=20 pounds. A weight gain of >/=20 pounds was significantly associated with increased total medical care costs in all subgroups evaluated. Among all subjects, for those who gained >/=20 pounds compared to those who maintained weight, the adjusted 3-y increase in costs was 561 dollars. Among the subgroup with baseline comorbidities, the adjusted 3-y change in total medical care costs was 711 dollars. Multivariate analyses showed no significant differences between those who gained 5-19 pounds and those who maintained weight. Baseline BMI and comorbidities were also significant predictors of change in medical care costs, independent of weight gain. CONCLUSION: A large 3-y weight gain (>/=20 lb) in middle-aged overweight and obese adults is associated with a correspondingly larger increase in total medical care costs compared to weight maintainers. The prevention of large weight gains holds promise for significantly reducing future medical care costs. Future studies should examine the causes of rapid weight gain and evaluate approaches to prevent and reverse such weight gain.

Development and validation of a measure of disease-specific quality of life in young children with haemophilia.

No disease-specific tool for measuring health-related quality of life (HRQL), an important outcome when assessing medical treatment, has been developed for children with haemophilia. The goal of this study was to develop a parent-administered questionnaire for evaluating quality of life (QOL) in paediatric haemophilia patients between 2 and 6 years of age. After interviewing physicians (5), nurses (5) and parents (10) of children with haemophilia aged between 2 and 6 years, 92 questions were developed and pilot-tested with parents (44) of children with haemophilia to create a 39-question instrument that assessed somatic symptoms, physical functioning, sleep disturbance, stigma, social functioning, fear/resentment, mood/behaviour, restrictions, treatment upset, haemophilia concern and energy level. Reliability and validity were evaluated with 103 parents of children with haemophilia and parents of 249 age- and gender-matched healthy children. Estimates of scale reliability (internal consistency) for eight multi-item scales ranged from 0.73 to 0.94. Results showed construct validity (correlations with age, severity of haemophilia, treatment type, days absent and days confined to bed) and correlated with two general, paediatric quality-of-life instruments (Impact on Family Scale and Functional Status II). Discriminant validity was demonstrated by comparing scores between patients receiving/not receiving prophylactic therapy and between haemophilia patients and healthy controls. This disease-specific HRQL measure should be of use in clinical trials and general practice to better understand disease and treatment impacts in young children with haemophilia.

Pattern formation and traveling waves in myxobacteria: theory and modeling.

Recent experiments have provided new quantitative measurements of the rippling phenomenon in fields of developing myxobacteria cells. These measurements have enabled us to develop a mathematical model for the ripple phenomenon on the basis of the biochemistry of the C-signaling system, whereby individuals signal by direct cell contact. The model quantitatively reproduces all of the experimental observations and illustrates how intracellular dynamics, contact-mediated intercellular communication, and cell motility can coordinate to produce collective behavior. This pattern of waves is qualitatively different from that observed in other social organisms, especially Dictyostelium discoideum, which depend on diffusible morphogens.

Venous thromboembolism following major orthopedic surgery: review of epidemiology and economics.

The epidemiology and economics of venous thromboembolism (VTE) associated with hip and knee arthroplasty and surgical repair of hip fracture are reviewed. In the 1960s and 1970s, prior to the widespread use of prophylaxis, the risk of VTE following major orthopedic surgery was substantial. The risk of fatal pulmonary embolism (PE) following hip fracture repair may have been as high as 7.5%. With improvements in surgical and anesthetic techniques and the use of anticoagulant prophylaxis, these risks have decreased significantly for most patients. Current risks after hip and knee arthroplasty appear to be about 2.5% for deep vein thrombosis, 1% for nonfatal PE, and a few tenths of 1% for fatal PE over a three-month period following surgery. Because of the traumatic nature of the injury, delays in getting to surgery, and their more advanced age and poorer overall health, hip fracture patients appear to have a greater risk of postoperative VTE, but data are lacking for a reliable estimate of current risk. The cost of VTE after major orthopedic surgery includes initial therapy (the chief component), follow-up care, and the expected costs of major hemorrhage (due to anticoagulation), recurrent VTE, and postthrombotic syndrome. The total cost per patient of such care is approximately $11,600. The risk of VTE after surgery to replace hip and knee joints and repair hip fracture is far lower today than in the 1960s and 1970s, but the cost of treating VTE remains high: an estimated $11,600 per patient, including hospitalization costs.

Cost-effectiveness results from the US Carvedilol Heart Failure Trials Program.

OBJECTIVE: To evaluate the cost-effectiveness of carvedilol, a beta-blocker that is approved for use in the US for the treatment of heart failure, based on data from Phase III clinical trials. METHODS: We conducted an economic evaluation alongside the US Carvedilol Heart Failure Trials Program, which consisted of four concurrent, randomized, double-blind, placebo-controlled clinical trials; the mean duration of follow-up across these four trials was 6.5 months (the program was terminated prematurely based on a finding of a 65% mortality benefit). Using data from these trials, we examined the cost-effectiveness of carvedilol in terms of the estimated cost per death averted among patients randomized to such therapy versus those receiving placebo. Attention was focused on the cost of carvediol therapy plus the cost of cardiovascular-related inpatient care. Costs of care were estimated by combining infomation on healthcare utilization from the clinical trials with secondary sources of cost data. RESULTS: Patients randomized to receive carvedilol had lower mean +/- SD estimated costs of cardiovascular-related inpatient care over 6.5 months compared with those receiving placebo ($1912 +/- $7595 vs. $4463 +/- $20,565, respectively). As mortality alsowas lower among carvedilol patients, the estimated cost per death averted was negative. The probability that carvedilol would both increase survival and decrease costs of cardiovascular-related care over a 6.5-month period was estimated to be 0.98. CONCLUSIONS: Data from the US Carvedilol Heart Failure Trials Program indicate that carvedilol reduces mortality in patients with heart failure; our study suggests that it also may be cost-saving over a period of approximately six months.