Safety assessment of an anti-obesity drug (sibutramine): a retrospective cohort study.

BACKGROUND: Obesity is a serious and rapidly growing health problem worldwide. Few therapies are available beyond diet, exercise and bariatric surgery. A previously approved medication, sibutramine, has been withdrawn from the market due to concerns over the potential of increased risk of cardiovascular (CV) events, based on a phase IV clinical trial that included only individuals at high risk for CV events. OBJECTIVE: The aim of the study was to compare sibutramine users and matched non-users on rates of CV events, both overall and stratified by whether the patient qualified for on-label sibutramine use, using data from real-life clinical practice. METHODS: A retrospective cohort was constructed from electronic medical record data from physician office practices (mostly primary care) in the UK and Germany, using the LifeLink™ database from IMS Health Incorporated. For patients with at least one physician visit in which sibutramine was prescribed between 1 April 1999 and 31 October 2008, the date of their first such prescription was their index date. Users and non-users were matched 1 : 1 on index date (within 30 days), sex, age group (six categories), Charlson Comorbidity Index and evidence of obesity (high body mass index [BMI] or, if BMI was missing, diagnosis of obesity or very high weight relative to height). The resultant total samples analysed were 6186 in Germany and 7264 in the UK. User and non-user cohorts in the samples were compared according to the ratio of their crude incidence rates of acute myocardial infarction (AMI), stroke and either AMI or stroke per 1000 patient-years of follow-up. Cox regression analysis was used to compare the risk of CV events as a hazard ratio (HR) with 95% confidence intervals (CIs) between sibutramine user and non-user cohorts, controlling for label status and/or history of prior CV disease at baseline. RESULTS: The risk of AMI, stroke and either AMI or stroke was not higher among sibutramine users than comparable non-users of sibutramine in both Germany and the UK [Germany: HR 0.47 (95% CI 0.17, 1.26), 0.43 (0.23, 0.81) and 0.44 (0.26, 0.75), respectively; UK: HR 0.44 (0.15, 1.31), 0.63 (0.25, 1.60) and 0.54 (0.27, 1.10), respectively]. Regardless of whether or not the model controlled for prior CV disease (CVD), the direction and statistical significance of the differences did not change. In the sensitivity analyses including only those without a history of CVD in the 365 days prior to the index date there was no increased risk of CV events in either Germany or the UK. CONCLUSION: This study offers a framework for the safety assessment of anti-obesity drugs using an observational epidemiological study design. Large electronic health databases were used to construct retrospective cohorts to examine the risk in a population using one specific anti-obesity drug. Use of sibutramine in general practice settings was not found to increase the risk of acute CV events.

Patterns of treatment with chemotherapy and monoclonal antibodies for metastatic colorectal cancer in Western Europe.

BACKGROUND AND OBJECTIVES: Treatment outcomes improved in metastatic colorectal cancer (mCRC) due to the introduction of new chemotherapies and monoclonal antibodies. This study describes current patterns of pharmacological treatment for mCRC in clinical practice in four European countries. METHODS: This cohort study used physician-survey data from the LifeLink Oncology Analyzer Database for mCRC patients in France, Germany, Italy and Spain. All patients aged ≥21 years at mCRC diagnosis and with data collected during 2009 were included. Treatment patterns were examined descriptively by lines of therapy. RESULTS: The study sample included 2682 mCRC patients. In first-line, more patients received FOLFOX (infusional 5-fluorouracil/leucovorin and oxaliplatin)- than FOLFIRI (infusional 5-fluorouracil/leucovorin and irinotecan)-, containing regimens in Germany (42 vs. 30%) and Spain (25 vs. 16%), while in Italy and France the reverse was true (Italy: 34% FOLFIRI vs.29% FOLFOX; France: 26 vs. 19%). In second-line, FOLFIRI-containing regimens were more commonly used than FOLFOX-containing regimens in Germany (36 vs. 18%), Italy (29 vs. 14%), and Spain (34 vs. 6%), while similar proportions of FOLFOX and FOLFIRI were used in France (18 vs. 15%). As part of first-line treatment, bevacizumab use ranged from 44% of patients in Italy to 30% in Spain, with slightly lower rates in second-line. Cetuximab first-line use ranged from 14% of patients in Spain to 7% in Italy, increasing in second-line to 30% in Spain, 26% in Italy, 20% in Germany, and 17% in France. LIMITATIONS: This analysis focused on description of treatment patterns, however, the actual clinical benefits of these treatment regimens on survival or quality of life were not addressed due to lack of relevant information in the data source. Some country differences in treatment patterns were observed. These differences might be partly explained by differences in local treatment guidelines, physician prescribing behaviours, reimbursement policies, and response to various regimens due to genetic differences. CONCLUSIONS: In clinical practice in four European countries, FOLFOX- and FOLFIRI-based regimens are common standard of care chemotherapies for mCRC (FOLFOX and bevacizumab + FOLFIRI are the most common regimens), and monoclonal antibodies are often combined with these chemotherapies.

Major surgery in patients with metastatic colorectal cancer in Western europe.

PURPOSE: Given the potential interference between treatment for metastatic colorectal cancer (mCRC) and surgical procedures, we sought to determine the prevalence of major surgery following mCRC diagnosis in clinical practice. METHODS: This cohort study used physician-surveyed data from the LifeLink™ Oncology Analyzer database for mCRC patients in five European countries (France, Germany, Italy, Spain, and the United Kingdom [UK]). All patients aged ≥21 years at mCRC diagnosis and with data collected during 2009 were included. Major surgical procedures were examined descriptively by the purpose and location of surgery. RESULTS: The study sample included 3,249 mCRC patients; 515, 862, 656, 649, and 567 were from France, Germany, Italy, Spain, and the UK, respectively. Following mCRC diagnosis, at least one major surgical procedure for any purpose was seen in 30.5% (UK), 35.2% (Germany), 35.6% (Spain), 36.3% (France), and 38.4% (Italy) of patients, with a mean of 1.3 (UK) to 1.6 (France) procedures. The rate of major surgery for curative purposes was the highest in Italy (13.4%), followed by France (12.8%), Spain (10.3%), and Germany (9.2%); the lowest was in the UK (7.2%). Major surgery performed on the primary tumor (12.4-27.1% of patients, depending on the country) and metastasis (6.4-14.6%) made up the majority of all surgical procedures. CONCLUSIONS: Major surgery is highly prevalent following mCRC diagnosis, suggesting an important role in meeting the goals of mCRC treatment. The role of pharmacological treatment options and their potential to interfere with both surgery use and surgical outcomes should be considered when evaluating mCRC treatment strategies.

One-year treatment persistence and potential adverse events among patients with atrial fibrillation treated with amiodarone or sotalol: a retrospective claims database analysis.

BACKGROUND: The risk-benefit profile of antiarrhythmic drugs (AADs) affects the choice of pharmacotherapy for maintenance of sinus rhythm. Adverse events (AEs) associated with AADs may influence patient compliance and compromise the management of atrial fibrillation (AF). There are limited data on the incidence of AEs or persistence with AADs outside the clinical trial environment. OBJECTIVE: This study provides treatment persistence and AE data for patients with AF receiving treatment with amiodarone or sotalol, 2 of the most widely used AADs in the United States. METHODS: In this retrospective cohort study, patients satisfying the following criteria were identified from the US MarketScan claims databases: (1) age ≥18 years with a pharmacy claim for oral amiodarone or sotalol between 2004 and 2007; (2) ≥1 inpatient/outpatient medical claim with an AF diagnosis <90 days before the earliest (index) pharmacy claim; and (3) ≥12 months' continuous enrollment before and after the index pharmacy claim. Prespecified AE rates were compared between treatment cohorts during active treatment. RESULTS: Among 77,093 AF patients with ≥1 claim for amiodarone or sotalol, 3459 met all inclusion criteria (mean age, 70.8 years; 61.6% male; mean Charlson Comorbidity Index [CCI], 1.58), of whom 2392 received amiodarone (mean age, 72.2 years; 62.5% male; mean CCI, 1.8) and 1067 received sotalol (mean age, 67.5 years; 59.7% male; mean CCI, 1.1). Persistence was higher among the sotalol cohort than the amiodarone cohort (53.2% vs 30.6% at 12 months; P < 0.001). Postindex versus preindex comparisons revealed increases in cardiovascular AE rates in both cohorts. Intercohort comparisons showed higher rates of cardiovascular AEs (594 vs 339 patients/1000 patient-years; P < 0.001) and pulmonary AEs (128 vs 61 patients/1000 patient-years; P < 0.001) during active amiodarone treatment. CONCLUSIONS: Among the population analyzed, patients with AF receiving amiodarone versus sotalol therapy had differing clinical characteristics. Patients experienced frequent AEs (particularly cardiovascular events) with amiodarone and sotalol, and many discontinued treatment during the first year.

Human growth hormone treatment: synthesis of literature on product delivery systems and administration practices.

PURPOSE: To synthesize current literature on recombinant human growth hormone (rhGH) use and to identify areas of research that have received little to no attention in light of administration practice and patient perception/behavior. DESIGN AND METHODS: Relevant articles for a systematic review were identified through PubMed. RESULTS: A total of 43 articles were identified: 9 (15.9%) studies on product administration practices and 34 (84.1%) on patient behavior patterns. Patients primarily preferred simple, convenient, and easy-to-use delivery devices. However, literature addressing the effect of convenient product administration practices on treatment outcomes using real-world patient/caregiver data is lacking. PRACTICE IMPLICATIONS: Better understanding of real-world product administration practices will help nurses identify areas of improvement in patient education and training.

Subacute lack of asthma control and acute asthma exacerbation history as predictors of subsequent acute asthma exacerbations: evidence from managed care data.

BACKGROUND: Monitoring indicators of subacute lack of asthma control (SALAC) may help to reduce asthma morbidity. OBJECTIVE: To determine whether SALAC, independent of current asthma exacerbations, is associated with subsequent acute asthma exacerbations. METHODS: Administrative claims data from PharMetrics/IMS Health were used to identify patients 12 years or older continuously enrolled in a participating U.S. health plan from 2001 to 2004 with >or=1 asthma claim (International Classification of Diseases, Ninth Revision, Clinical Modification code 493.x), no chronic obstructive pulmonary disease or cystic fibrosis claims, and >or=1 prescription for an asthma medication during 2001-2004. SALAC was defined as more than 4 asthma-related physician visits (or >or=2/quarter) or more than 5 short-acting beta((2))-adrenergic agonist prescriptions during 2001. Effect of asthma control category (Exacerbation Only [EO], SALAC Only [SO], Both Exacerbation and SALAC [Both], Neither Exacerbation nor SALAC [Neither]) in 2001 on acute asthma exacerbations (hospitalization, emergency department visit, or short-term oral corticosteroid use) during 2002-2004 was assessed using logistic regression, adjusting for gender, age, health plan type, and region. RESULTS: Of 11,779 patients, 8% were assigned to the EO group, 26% to SO, 12% to Both, and 54% to Neither in 2001. The incidence of exacerbations in 2002-2004 was higher for Both (61.8%) versus EO (55.0%) and for SO (37.3%) versus Neither (31.9%). The risk of exacerbation in 2002-2004 was increased significantly (p < .0001) for Both (3.394; 95% confidence interval [CI] = 3.009, 3.827), EO (2.503; 95% CI = 2.176, 2.879), and SO (1.277; 95% CI = 1.166, 1.399) versus Neither. CONCLUSION: In this study, the risk of subsequent exacerbation was greatest in patients with both SALAC and acute asthma exacerbations, followed by those with exacerbations only and those with SALAC only. SO identified an additional 26% of asthma patients at increased risk for subsequent exacerbation. The results from this study demonstrate that SALAC indicators and a history of acute asthma exacerbations are independent predictors of future acute asthma exacerbations and highlight the important role of subacute asthma worsening in predicting and preventing future asthma exacerbations.

Patterns and predictors of discontinuation of rhythm-control drug therapy in patients with newly diagnosed atrial fibrillation.

STUDY OBJECTIVE: To assess patterns and predictors of discontinuation of rhythm-control drug therapy in managed care patients with newly diagnosed atrial fibrillation and the direct medical costs of atrial fibrillation in these patients. DESIGN: Retrospective cohort study. DATA SOURCE: PharMetrics Patient-Centric Database. PATIENTS: A total of 3549 adults with a new diagnosis of atrial fibrillation between April 1, 2002, and March 31, 2006, and who had at least one claim for rhythm-control drug therapy within 6 months of the initial diagnosis. MEASUREMENTS AND MAIN RESULTS: Discontinuation (defined as a gap in rhythm-control drug therapy coverage [days' supply] > or = 30 days) was assessed after the initiation of rhythm-control therapy. Among the 3549 patients included in the analysis, 2688 (75.7%) discontinued initial rhythm-control therapy in the first 12 months, with a median time to discontinuation of 89 days. Significant predictors of rhythm-control therapy discontinuation included cardiac arrest (odds ratio [OR] 2.24, 95% confidence interval [CI] 1.04-4.83), history of coronary artery bypass graft surgery (OR 2.03, 95% CI 1.02-4.05), valvular heart disease (OR 1.67, 95% CI 1.33-2.09), ischemic heart disease (OR 1.44, 95% CI 1.13-1.82), and severity of illness (Charlson Comorbidity Index score; OR 1.09, 95% CI 1.01-1.17). Over 12 months, 661 (18.6%) of the 3549 patients had a hospital stay and 285 (8.0%) had an emergency department visit that were related to atrial fibrillation. Total annual atrial fibrillation-related costs/patient were $6165: $3872 for inpatient costs, $1503 for outpatient costs, and $790 for pharmacy costs. CONCLUSION: Initial rhythm-control drug therapy is associated with a high rate of discontinuation, especially early in therapy. Such rates of discontinuation will likely have an impact on the effectiveness of disease management and the quality of care in patients with atrial fibrillation.

Cost-effectiveness of Roux-en-Y gastric bypass in type 2 diabetes patients.

OBJECTIVE: To assess the cost-effectiveness of Roux-en-Y gastric bypass for treating type 2 diabetes mellitus (T2DM) in the United States compared with standard medical management, using clinical data from a prospective observational study conducted at an academic medical center. STUDY DESIGN: Our study used a predictive health economic model (the CORE Diabetes Model) to project the long-term costs and clinical effectiveness of Roux-en-Y gastric bypass as a treatment for T2DM using the prospective observational study as the basis for our clinical effectiveness assumptions. METHODS: The CORE Diabetes Model used Monte Carlo simulation with tracker variables to estimate the lifetime costs and clinical outcomes of Roux-en-Y gastric bypass compared with standard medical management of obese T2DM patients. Sensitivity analyses were performed on key clinical assumptions, discount rates, and shorter time horizons. RESULTS: The base-case scenario yielded an incremental cost-effectiveness ratio (ICER) of $21,973 per quality-adjusted life-year (QALY) gained. In sensitivity analyses, shortening the time horizon to 5 and 10 years and excluding the negative impact of increased body mass index on the patient's quality of life had the greatest adverse impact on the ICERs (ie, higher cost per QALY). CONCLUSIONS: Under base-case assumptions, Roux-en-Y gastric bypass is cost-effective in the treatment of T2DM in the United States with an ICER below $50,000 per QALY gained. Sensitivity analyses indicated that bariatric surgery is not cost-effective over shorter time horizons, or if the negative quality-of-life impact of increased body mass index is ignored.

Cost of hospital admission for antiarrhythmic drug initiation in atrial fibrillation.

BACKGROUND: Initiation of some rhythm-control therapies for atrial fibrillation (AF) requires an inpatient hospital stay and telemetry monitoring, adding to the cost burden of AF. However, specific cost data for inpatient initiation of AF therapies are lacking. OBJECTIVE: To examine costs associated with initiating sotalol or dofetilide in the inpatient setting in the US. METHODS: This retrospective cohort study used data from billing/discharge records in the Premier Perspective Database for adults with a primary diagnosis of AF, hospitalized between January 2002 and September 2007. Patients had to have received 4 or more sotalol doses or 5 or more dofetilide doses starting within 2 days of admission (with >/=1 dose within 3 days of discharge). Patients admitted solely for AF drug initiation were identified by excluding patients who were admitted on an emergency basis, received care in the emergency department, or underwent major surgical procedures. The primary outcome was direct medical costs for in-hospital services during the stay. RESULTS: Among 7290 patients included in the analysis (4847 sotalol, 2443 dofetilide), mean total inpatient costs per patient were $3278 in the sotalol group and $3610 in the dofetilide group. The greatest costs were for room/board ($1874 sotalol, $1985 dofetilide) and cardiology/electrocardiograms ($394 sotalol, $443 dofetilide). Pharmacy costs were $230 and $201 per patient in the sotalol and dofetilide groups, respectively. CONCLUSIONS: The admission of patients for in-hospital initiation of AF rhythm-control therapy represents a high cost burden in the US.

Differences in annual medication costs and rates of dosage increase between tumor necrosis factor-antagonist therapies for rheumatoid arthritis in a managed care population.

BACKGROUND: Tumor necrosis factor (TNF) antagonists are commonly used to treat rheumatoid arthritis (RA). Differences in the dosage and mode of administration of these agents may result in differential rates of dosage adjustment and costs of care. OBJECTIVE: This study compared dosing patterns and annual costs associated with the use of the subcutaneous TNF antagonists adalimumab and etanercept, and the intravenous TNF antagonist infliximab. METHODS: A large managed care database (PharMetrics) was used to identify patients with RA who newly initiated TNF-antagonist therapy with adalimumab, etanercept, or infliximab on or after January 1, 2003, and had at least 6 months of continuous health plan enrollment before initiation of therapy and 12 months of continuous enrollment after initiation. The patients were followed over 12 months of enrollment. Annual pharmacy, inpatient, and outpatient costs were estimated based on plan reimbursements and were compared between cohorts. The average daily dosage (ADD) between prescription refills was used to compare the percentages of patients with greater-than-expected dosing (GTED), defined as 2 consecutive increases in ADD relative to the patient's established maintenance dosage. RESULTS: A total of 2382 patients (568 adalimumab, 1181 etanercept, 633 infliximab) were included in the analysis. Significantly more patients had GTED with infliximab compared with adalimumab and etanercept (32.1%, 8.5%, and 4.7%, respectively; both comparisons, P < 0.05). For patients with a dosage increase, the mean time to the first GTED was significantly shorter for infliximab compared with adalimu-mab and etanercept (154.5, 173.3, and 167.9 days; both, P < 0.05). The mean annual costs of anti-TNF therapy, adjusted for baseline differences, were significantly greater for infliximab compared with adalimumab and etanercept ($15,617, $12,200, and $12,146; both, P < 0.05). There were also significant differences between infliximab relative to adalimumab and etanercept in total RA-related medication costs ($16,280, $12,989, and $12,794; P < 0.05) and total pharmacy costs ($17,854, $14,805, and $14,398; P < 0.05). CONCLUSION: Patients initiating TNF-antagonist treatment for RA with infliximab incurred annual medication costs that were nearly 30% greater than costs in those initiating therapy with adalimumab or etanercept, in part because of the significantly greater rate of GTED in infliximab recipients.

Economic burden of transformed migraine: results from the American Migraine Prevalence and Prevention (AMPP) Study.

OBJECTIVE: To evaluate the impact of incident transformed migraine on health care resource utilization, medication use, and productivity loss. In addition, the study estimates the total direct and indirect costs associated with transformed migraine. BACKGROUND: Emerging evidence indicates that migraine may be a chronic progressive disorder characterized by escalating frequency of headache attacks, often termed transformed migraine. Little is known about the economic impact of transformed migraine. METHODS: AMPP is a 5-year, national, longitudinal survey study of headache in the US. The study utilized data from the 2006 follow-up survey based on an initial sample of 14,544 adults identified as having migraine in either the 2004 screening or 2005 baseline survey. A diagnosis of migraine was assigned based on criteria proposed by the International Classification of Headache Disorders, 2nd Edition. Participants completed self-administered, validated questionnaires on headache features, frequency, impairment, resource use, medication use, and productivity loss. Direct and indirect headache-related costs were estimated using unit cost assumptions from the PharMetrics Patient-Centric database, wholesale acquisition costs (Red Book), and wage data from the US Bureau of Labor Statistics. Those who developed transformed migraine were compared with those who did not develop transformed migraine in the 1-2 year interval between screening/baseline and follow-up. RESULTS: A total of 7796 (54%) identified migraine cases completed the 2006 follow-up survey. Of those cases, 359 (4.6%) developed transformed migraine. Participants who developed transformed migraine reported significantly more primary care visits, neurologist or headache specialist visits, pain clinic visits, and emergency room visits compared with participants whose migraine remained episodic. Hospital nights and urgent care visits did not reach statistical significance. Transformed migraine participants reported significantly more time missed at work or school because of headaches and more time where work or school productivity was reduced by >50% in the previous 3 months because of headaches. Average per-person annual total costs, including direct and indirect costs, were 4.4-fold greater for those who developed transformed migraine ($7750) compared with those who remained episodic ($1757). CONCLUSION: Transformed migraine exacts a significantly higher economic toll on patients and health care systems compared with other forms of migraine. Our findings support the need to prevent migraine progression and to provide appropriate management and treatment of transformed migraine.

Estimated prevalence of uncontrolled hypertension and multiple cardiovascular risk factors and their associated risk of coronary heart disease in the United States.

This study determined the prevalence of primary prevention patients aged 40 to 79 years with uncontrolled hypertension (HTN) and low/moderate cholesterol levels, and the clinical and economic consequences of their cardiovascular risk levels stratified by additional cardiovascular risk factors. Prevalence was estimated from the 1999 to 2002 National Health and Nutrition Examination Survey (NHANES) datasets. Framingham risk equations were used to calculate the 4-year risk of coronary heart disease (CHD). HTN and cholesterol levels were then statistically "controlled" to ideal levels and risks were recalculated. Prevalence of uncontrolled hypertension was 15.2 million cases (13.7%). Of those, 12.9 million (84.8%) had low/moderate cholesterol levels, and 2.2 million (16.7%) had >/=3 additional risk factors with no history of CHD. Nearly 200,000 coronary events are expected to occur within 4 years, incurring over $2.5 billion in direct medical costs. Statistical estimation suggests that 64% of 4-year risk was attributable to uncontrolled blood pressure and lipids. The large number and high cost of CHD events expected to occur within the next 4 years in primary prevention patients with uncontrolled hypertension and >/=3 additional risk factors justifies aggressive screening to ensure that these patients are identified and properly managed.

Predictors of bipolar disorder risk among patients currently treated for major depression.

OBJECTIVE: The primary objective of this study was to assess the rate of bipolar disorder (BPD) risk among patients unsuccessfully treated for major depression and to identify predictors of bipolarity. PATIENTS, DESIGN, AND SETTING: Psychiatrists from community and private practice settings sequentially selected patients with unipolar depression who exhibited nonresponse to at least 1 antidepressant (AD) trial. MAIN OUTCOME MEASURES: Patients self-reported their demographics, family history, comorbid health status, and legal problems. Current depression symptoms were assessed via the Centers for Epidemiologic Studies--Depression (CES-D) scale. Bipolar screening was performed using the Mood Disorder Questionnaire (MDQ). A psychiatrist recorded patient history and current and prior AD medication use. RESULTS: Of 602 patients enrolled, 18.6% screened positive on the MDQ. This rate was not affected by the number of prior AD failures or patient demographics. A prior history of BPD was reported by 12.3% of patients of which the psychiatrist was not aware or did not report, and 41.2% of these patients were MDQ+. Stepwise logistic regression identified 5 variables associated with bipolar disorder risk: the CES-D item "people were unfriendly," comorbid anxiety, initial depression diagnosis within 5 years, family history of BPD, and legal problems. In the subset of patients with complete data for the 5 variables (n = 483), 41.3% of the patients endorsing any 3 or more risk factors (n = 109) were MDQ+. CONCLUSIONS: Almost 20% of patients with AD nonresponsive unipolar depression screened positive for BPD and the number of past medication trials had no effect on bipolarity. This suggests that clinicians should carefully screen for BPD in patients who have failed at least 1 antidepressant. Comorbid anxiety, feelings of people being unfriendly, recent depression diagnosis, BPD family history, and legal problems may prove useful indicators of BPD risk among patients who have failed at least 1 antidepressant. Future studies are needed to confirm that these risk factors are useful clinical variables to screen for bipolarity.

Cost-effectiveness of rosuvastatin compared with other statins from a managed care perspective.

OBJECTIVE: The objective of this study was to identify the most cost-effective statin or combination of statins, from the perspective of a managed care payer. METHODS: A decision-analytic model compared the cost-effectiveness of titration to goal with atorvastatin, fluvastatin, lovastatin, pravastatin, rosuvastatin, and simvastatin in patients with elevated low-density lipoprotein cholesterol (LDL-C). Effectiveness measures included the percentage change from baseline LDL-C and high-density lipoprotein cholesterol (HDL-C), and the percentage of patients achieving National Cholesterol Education Program (NCEP) Second Adult Treatment Panel (ATP II) LDL-C goals. Direct medical costs were calculated based on drug, physician, and laboratory resource use, multiplied by wholesale acquisition costs for drugs and the 2005 Medicare reimbursement rates for services. A Monte Carlo simulation tested the sensitivity of results to model efficacy inputs. RESULTS: In the base-case analysis, rosuvastatin dominated atorvastatin, pravastatin, and simvastatin. Generic lovastatin dominated fluvastatin. The incremental (absolute) reduction in LDL-C, increase in HDL-C, and increase in patients to goal with rosuvastatin compared with lovastatin were 16%, 3%, and 27%, respectively. Incremental costs per additional 1% reduction in LDL-C, 1% increase in HDL-C, and patient to goal with rosuvastatin versus lovastatin were $8, $41, and $436, respectively. A wide variety of assumptions were assessed and Monte Carlo sensitivity analyses were conducted. Findings were most sensitive to the cost of lovastatin. CONCLUSION: Rosuvastatin dominates atorvastatin, pravastatin, and simvastatin because it is more effective and less costly, and it may be considered cost-effective compared with generic lovastatin. The most cost-effective two-statin formulary contained lovastatin and rosuvastatin.

Gauging the treatment gap in dyslipidemia: findings from the 1999-2000 National Health and Nutrition Examination Survey.

BACKGROUND: Despite published guidelines and availability of many effective lipid-altering therapies, dyslipidemia in the United States remains largely underdiagnosed and undertreated. METHODS: This study used data from the 1999-2000 National Health and Nutrition Examination Survey to assess the current state of dyslipidemia management in the US adult population compared with guidelines issued by the Third Adult Treatment Panel of the National Cholesterol Education Program. Percentages were weighted to reflect population estimates, computed using SUDAAN (Research Triangle Institution, Cary, NC). RESULTS: Among 1,425 respondents aged > or = 20 years with complete data, 29.5% were eligible for therapeutic lifestyle changes (TLCs, 16.0%) or lipid-lowering drug therapy (LDT, 13.4%). Among high-risk adults, 79.3% were eligible for either TLC (35.7%) or LDT (43.6%). Only 43.7% of treatment-eligible adults reported ever being diagnosed with dyslipidemia. Of those diagnosed, 77.4% reported being told to undertake TLC, and 34.2% reported being told to take LDT. Of adults eligible for drug therapy, the average percentage reduction in low-density lipoprotein cholesterol (LDL-C) required to reach goal was 28.0% (standard error [SE] 1.1), and 41.9% required a reduction of > 30% in LDL-C to reach goal. Of high-risk adults eligible for drug therapy, the average required reduction was 36.9% (SE 1.4), and 76.3% required a reduction of > 30% in LDL-C. CONCLUSIONS: Despite advances in dyslipidemia therapy and changes in guidelines over the last decade, LDL-C continues to be inadequately managed among US adults. Of particular concern is the undertreatment of high-risk patients and failure of many treated patients to achieve LDL-C goal.