Network meta-analysis of pembrolizumab as monotherapy and in combination with chemotherapy for first-line treatment of recurrent or metastatic head and neck squamous cell carcinoma / Metanálise em rede comparativa de pembrolizumabe como monoterapia e em combinação com quimioterapia para tratamento de primeira linha de carcinoma de células escamosas da cabeça e pescoço recorrente ou metastático

Pembrolizumab monotherapy or in combination with chemotherapy is approved as first-line treatment in recurrent/metastatic head and neck squamous cell carcinoma (R/M HNSCC) based on improved overall survival (OS) versus EXTREME regimen in the KEYNOTE-048 trial. The clinical outcomes of pembrolizumab were compared with other recommended first-line treatments in R/M HNSCC in this study through a Bayesian network meta-analysis. A systematic literature review was conducted in July 2022, from which six trials that matched the KEYNOTE-048 patient eligibility criteria were included in the network. The OS and progression-free survival (PFS) outcomes were compared in the approved pembrolizumab indication (i.e., total population for pembrolizumab in combination with chemotherapy and combined positive score [CPS] ≥ 1 population for pembrolizumab monotherapy). A significant OS improvement was observed for pembrolizumab in combination with chemotherapy and pembrolizumab monotherapy versus EXTREME regimen (hazard ratio, 95% credible interval: 0.72, 0.60-0.86; 0.73, 0.60-0.88), platinum+5- FU (0.58, 0.43-0.76; 0.58, 0.44-0.78), and platinum+paclitaxel (0.53, 0.35-0.79; 0.53, 0.35-0.81), respectively. A non-significant numeric trend in OS improvement was observed versus the TPEx regimen. PFS was comparable with most first-line treatments and was improved versus platinum+5-FU (0.48, 0.36-0.64; 0.59, 0.45-0.79). Additional analyses in higher CPS subgroups also showed consistent results. Overall, our study results showed an improvement in OS outcomes versus alternative first-line treatments, consistent with the findings of the KEYNOTE-048 trial. These data support using pembrolizumab as a suitable firstline treatment option in R/M HNSCC.

Pembrolizumabe em monoterapia ou em combinação com quimioterapia é aprovado como tratamento de primeira linha em carcinoma de células escamosas recorrente/metastático de cabeça e pescoço (CECCP R/M) com base na melhora da sobrevida global (OS), em comparação com o esquema EXTREME no estudo KEYNOTE-048. Esse estudo comparou os resultados clínicos de pembrolizumabe com outros tratamentos recomendados de primeira linha em CECCP R/M por meio de uma metanálise de rede bayesiana. Uma revisão sistemática da literatura foi conduzida em julho de 2022, a partir da qual seis ensaios clínicos que atendiam aos critérios de elegibilidade de pacientes do KEYNOTE-048 foram incluídos na rede. Os desfechos de OS e sobrevida livre de progressão (PFS) foram comparados na indicação de pembrolizumabe (população total para pembrolizumabe em combinação com quimioterapia e população com escore positivo combinado [CPS] ≥ 1 em monoterapia com pembrolizumabe). Foi observada melhora significativa na OS para pembrolizumabe em combinação com quimioterapia e monoterapia com pembrolizumabe versus o esquema EXTREME (razão de risco, intervalo de confiança de 95%: 0,72, 0,60-0,86; 0,73, 0,60-0,88), platina+5-FU (0,58, 0,43-0,76; 0,58, 0,44-0,78) e platina+paclitaxel (0,53, 0,35-0,79; 0,53, 0,35-0,81), respectivamente. Uma tendência numérica não significativa de melhoria na OS foi observada em relação ao esquema TPEx. A PFS foi comparável com a maioria dos tratamentos de primeira linha e melhor em relação à platina+5-FU (0,48, 0,36-0,64; 0,59, 0,45-0,79). Análises adicionais em subgrupos com CPS mais elevado também mostraram resultados consistentes. No geral, os resultados de nosso estudo mostraram melhora nos desfechos de OS em comparação aos tratamentos de primeira linha alternativos, consistentes com os achados do estudo KEYNOTE-048. Esses dados apoiam o uso de pembrolizumabe como opção de tratamento em primeira linha em pacientes com CECCP R/M.

Incidence of Acute Neurological Events in Neonates and Infants Undergoing Cardiac Surgery Using a High-Hematocrit/ High-Flow Bypass Strategy.

Background: The incidence of new acute neurological injury occurring in neonates and infants during cardiac surgery utilizing cardiopulmonary bypass is reportedly 3% to 5%. In 2013, we adopted a high flow rate, and high hematocrit bypass strategy, and sought to assess the incidence of early neurological injuries associated with this strategy. Methods: Neonates and infants undergoing cardiopulmonary bypass between January 2013 and December 2019 (n = 714) comprise the study. Adverse neurological events (ANEs) were defined as any abnormality of pupils, delayed awakening, seizures, focal neurological deficits, concerns prompting neurological consultation, or any abnormality on neurological imaging in the postoperative period. Our bypass strategy included a high flow rate (150-200 mL/kg/min), without reduction of flow rates during cooling and maintaining a target hematocrit on bypass > 32% with a terminal hematocrit of > 42%. Results: Median weight at the time of the procedure was 4.6 kg (IQR 3.6-6.1 kg) with the smallest patient weighing 1.36 kg. There were 46 premature patients (6.4%). There were 149 patients (20.9%) patients who underwent deep hypothermic circulatory arrest with a median time of 26 min (IQR 21-41 min). Hospital mortality was 3.5% (24/714, 95% CI: 2.28-5.13). The incidence of neurological events as defined above was 0.84% (6/714, 95% CI: 0.31-1.82). Neurological imaging identified ischemic injury in 4 patients and intraventricular hemorrhage in 2. Conclusions: High flow/high hematocrit bypass strategy was associated with a low incidence of ANE in this vulnerable population.

Cost-effectiveness of pembrolizumab for the first-line treatment of recurrent or metastatic head and neck squamous cell carcinoma in the United States.

AIMS: Pembrolizumab, as monotherapy in first-line recurrent or metastatic (R/M) head and neck squamous cell carcinoma (HNSCC) with a combined positive score (CPS) ≥1 and in combination with platinum and 5-fluorouracil (5-FU) in the overall R/M HNSCC population, received US FDA approval based on the KEYNOTE-048 trial. Using public drug prices, from a US payer perspective, we evaluated the cost-effectiveness of each pembrolizumab regimen vs. cetuximab + platinum+5-FU (EXTREME regimen, trial comparator), cisplatin + docetaxel + cetuximab (TPEx regimen), cisplatin + paclitaxel, and platinum+5-FU. METHODS: A three-state partitioned-survival model was used to project costs and outcomes over 20 years with 3% annual discounting. Progression-free and overall survival were modeled using long-term extrapolation of KEYNOTE-048 data and, for alternative comparators, data from a network meta-analysis was used. Time-on-treatment was derived from KEYNOTE-048 or approximated using network meta-analysis progression-free survival estimates. Costs included first-line and subsequent treatments, disease management, adverse events, and terminal care costs. Utilities were derived from the KEYNOTE-048 Euro-QoL five-dimension data and using a US algorithm. RESULTS: In the CPS ≥1 R/M HNSCC population, pembrolizumab monotherapy was dominant vs. EXTREME and TPEx regimens, and cost-effective (at $100,000/QALY threshold) vs. platinum+5-FU ($86,827/QALY) and cisplatin + paclitaxel ($81,473/QALY). Pembrolizumab combination therapy in the overall R/M HNSCC population was dominant vs. TPEx regimen, and cost-effective vs. EXTREME regimen ($1769/QALY), platinum+5-FU ($81,989/QALY), and cisplatin + paclitaxel ($89,505/QALY). Sensitivity analyses showed a high cost-effectiveness probability for pembrolizumab at the $100,000/QALY threshold. CONCLUSIONS: First-line pembrolizumab monotherapy in patients with CPS ≥1, and pembrolizumab combination therapy in the overall R/M HNSCC population is cost-effective from the perspective of the US payers.

Clinical and Economic Outcomes in Patients with Persistent Asthma Who Attain Healthcare Effectiveness and Data Information Set Measures.

BACKGROUND: Attainment of asthma-specific US Healthcare Effectiveness Data and Information Set (HEDIS) quality measures may be associated with improved clinical outcomes and reduced economic burden. OBJECTIVE: We examined the relationship between the attainment of HEDIS measures asthma medication ratio (AMR) and medication management for people with asthma (MMA) on clinical and economic outcomes. METHODS: This retrospective claims database analysis linked to ambulatory electronic medical records enrolled US patients aged ≥5 years with persistent asthma between May 2015 and April 2017. The attainment of AMR ≥0.5 and MMA ≥75% was determined over a 1-year premeasurement period. Asthma exacerbations and asthma-related health care costs were evaluated during the subsequent 12-month measurement period, comparing patients attaining 1 or both measures with those not attaining either. RESULTS: In total, 32,748 patients were included, 75.2% of whom attained AMR (n = 24,388) and/or MMA (n = 12,042) during the premeasurement period. Fewer attainers of 1 or more HEDIS measures had ≥1 asthma-related hospitalizations, emergency department visit, corticosteroid burst, or exacerbation (4.9% vs 7.3%; 9.6% vs 18.2%; 43.8% vs 51.6%; 14.3% vs 23.3%, respectively; all P < .001) compared with nonattainers. In adjusted analyses, HEDIS attainment was associated with a lower likelihood of exacerbations (odds ratio: 0.63, [95% confidence interval: 0.60-0.67]; P < .001). The attainment of ≥1 HEDIS measures lowered total and asthma-related costs, and asthma exacerbation-related health care costs per patient relative to nonattainers (cost ratio: 0.87, P < .001; 0.96, P = .02; and 0.59, P < .001, respectively). Overall and asthma-specific costs were lower for patients attaining AMR, but not MMA. CONCLUSIONS: HEDIS attainment was associated with significantly improved asthma outcomes and lower asthma-specific costs.

Asthma control is associated with economic outcomes, work productivity and health-related quality of life in patients with asthma.

BACKGROUND: The objective of this analysis was to examine the association between asthma control (based on Asthma Control Test (ACT) responses) and healthcare resource utilisation (HRU), work productivity and health-related quality of life (HRQoL) among a nationwide sample of US adults with a self-reported diagnosis of asthma and without comorbid chronic obstructive pulmonary disease. METHODS: Data were obtained from the 2015 and 2016 self-administered, internet-based National Health and Wellness Surveys. Patients were grouped by ACT score (≤15: poorly controlled; 16-19: partly controlled; 20-25: well-controlled asthma). Study outcomes included HRU (patient-reported healthcare provider visits, emergency department visits and hospitalisations during the previous 6 months); work productivity, measured using the Work Productivity and Activity Impairment-General Health Scale; HRU-associated costs and work productivity loss and HRQoL, measured using EuroQoL-5 Dimensions-5 Levels (EQ-5D-5L) and the Short Form Health Survey-36V.2 (SF-36V.2). Incremental differences in outcomes between groups were assessed using generalised linear models adjusted for covariates. RESULTS: Of 7820 eligible adults, 17.4% had poorly controlled, 20.1% partly controlled and 62.5% well-controlled asthma. Well-controlled asthma was associated with significantly lower HRU (p<0.001) and lower mean direct costs ($6012 vs $8554 and $15 262, respectively; p<0.001); well-controlled asthma was also associated with significantly lower mean scores for work absenteeism, work presenteeism, overall work impairment and activity impairment (all p<0.001), and lower mean indirect costs ($6353 vs $10 448 and $14 764, respectively; p<0.001). Clinically meaningful differences favouring well-controlled asthma were seen for all HRQoL measures, with statistically significantly higher adjusted mean EQ-5D-5L index and SF-6D Health Utilities Index scores (derived from SF-36V.2) for patients with well-controlled asthma compared with partly controlled or poorly controlled asthma (p<0.001). CONCLUSIONS: The study demonstrates a clear relationship between asthma control and its impact on HRU, costs, work productivity and HRQoL. This will allow for better identification and management of patients with poorly controlled asthma.

Symptomatic Tetralogy of Fallot in Young Infants: Primary Repair or Shunt-Pediatric Health Information System Database Analysis.

BACKGROUND: Compare the early outcomes and hospital charges of early primary repair and systemic-to-pulmonary artery shunt for neonates and young infants (≤90 days of age) with tetralogy of Fallot using data from the Pediatric Health Information System database. METHODS: The Pediatric Health Information System database was queried for patients <90 days of age with primary diagnosis of tetralogy of Fallot who underwent nonelective surgical repair or palliation between January 2008 and December 2014. The initial cohort of 821 patients (group 1 early primary repair, N = 554; group 2 systemic-to-pulmonary artery shunt, N = 267) was propensity score matched (248 patients in each group) to account for baseline imbalances in age and prostaglandin use. RESULTS: Comparison of unmatched groups revealed younger age and higher incidence of extracardiac anomalies ( P = .02) and prematurity ( P = .04) in group 2. Mortality was comparable between the groups (group 1: 20 [4%] of 554 vs group 2: 11 [4%] of 267, P = .74). Irrespective of the type of procedure, prematurity (odds ratio [OR] = 3.3, 95% confidence interval [CI]: 1.5-7.4) and extracardiac anomalies (OR = 2.5, 95% CI: 1.2-5.3) were independent risk factors for mortality. Propensity score-matched analysis revealed no significant differences in patient mortality ( P = 1), duration of ventilation ( P = .64), hospital length of stay ( P = .69), or hospital charges ( P = .08) between the two groups. CONCLUSION: Outcomes and hospital charges associated with nonelective early primary repair are comparable to systemic-to-pulmonary artery shunt in symptomatic patients <90 days old with tetralogy of Fallot.

The economic impact of improving phosphate binder therapy adherence and attainment of guideline phosphorus goals in hemodialysis patients: a Medicare cost-offset model.

INTRODUCTION: Hyperphosphatemia (serum phosphorus >5.5 mg/dL) in hemodialysis patients is a key factor in mineral and bone disorders and is associated with increased hospitalization and mortality risks. Treatment with oral phosphate binders offers limited benefit in achieving target serum phosphorus concentrations due to high daily pill burden (7-10 pills/day) and associated poor medication adherence. The economic value of improving phosphate binder adherence and increasing percent time in range (PTR) for target phosphorus concentrations has not been previously assessed in dialysis patients. The current retrospective analysis was conducted to summarize health care cost savings to United States (US) payers associated with improved phosphate binder adherence and increased PTR for target phosphorus concentrations in adult end-stage renal disease (ESRD) patients receiving hemodialysis therapy. METHODS: Phosphate binder adherence and PTR were derived from hemodialysis patients who were treated at a large dialysis organization between January 2007 and December 2011. Cost model inputs were derived from US Renal Data System data between July 2007 and December 2009. A cost-offset model was constructed to estimate monthly and annual incremental health care costs (total Medicare; inpatient, outpatient, and Medicare Part B) associated with different levels of phosphate binder adherence and PTR. Model inputs included number of ESRD patients, population adherence to phosphate binders, PTR associated with adherence to phosphate binders, and per-patient per-month cost associated with PTR. A base case model estimated monthly and annual costs of phosphate binder therapy in the population using estimated model inputs. The estimated adherence rate was used to determine number of patients in compliant and noncompliant groups. Monthly costs were calculated as the sum of per-patient per-month cost times the number of patients in adherent and nonadherent groups. Annual costs were monthly costs times 12 and assumed the same level of adherence, PTR, and per-patient per-month costs over time. To study the impact of improving phosphate binder adherence and PTR on cost outcomes, we hypothetically and simultaneously increased both base phosphate binders adherence and PTR for adherent patients (adherence/PTR: 10/20%, 20/40%, 30/60%). Monthly and annual costs were derived for each scenario and compared against the results of the base case model. One-way sensitivity analysis was performed to test model robustness. RESULTS: The base case model estimated total Medicare and inpatient costs of $5,152,342 and $1,435,644, respectively (N = 1,000). When base case model costs were compared to results of each extended model scenario, overall Medicare cost savings (range 0.3-1.9%) and inpatient cost savings (range 1.2-5.7%) were observed. The one-way sensitivity analysis indicated that results were sensitive to PTR for adherent and nonadherent patients and the factor used to increase adherence rate and PTR associated with adherence in the hypothetical scenarios. However, cost savings in overall Medicare costs and inpatient costs were still noted. CONCLUSION: Increasing phosphate binder adherence and improving phosphorus control were associated with increased cost savings in total Medicare costs and inpatient costs.

Persistence with nebivolol in the treatment of hypertension: a retrospective claims analysis.

OBJECTIVE: Examine drug persistence by evaluating the hazard of discontinuation and of switching to different antihypertensive drugs in patients initiating treatment with a recently approved ß-blocker, nebivolol, versus other ß-blockers. METHODS: This retrospective analysis included all patients diagnosed with hypertension in the MarketScan Database (January 2007 - December 2008) with at least two medical claims and no prior ß-blocker prescriptions within 6 months of the initial prescription date. Multivariate Cox proportional hazard models (adjusted for baseline differences in demographics, previous use of other antihypertensive medications, initial doses and supply of medication, and number of distinct prescriptions at baseline) were used to assess the hazard of discontinuation, defined as the first prescription gap of ≥30 days, and to assess the hazard of switching to another antihypertensive drug, defined as a prescription fill for another antihypertensive drug within 15 days before and 30 days after discontinuation of the initial ß-blocker. RESULTS: Of the 173,200 patients included in the study population, the adjusted hazard of discontinuation for nebivolol-initiated patients was 8-20% lower than that of patients who initiated treatment with atenolol (hazard ratio [HR] 0.82, p < 0.001), metoprolol (HR 0.91, p < 0.001), carvedilol (HR 0.92, p < 0.001), or other ß-blockers (HR 0.80, p < 0.001). The adjusted hazard of nebivolol-treated patients switching to a different antihypertensive medication was 12-22% lower than that of the other four ß-blocker cohorts (atenolol: HR 0.80, p < 0.001; metoprolol: HR 0.86, p < 0.001; carvedilol: HR 0.88, p < 0.001; other ß-blockers: HR 0.78, p < 0.001). Sensitivity analyses defined discontinuation as prescription gaps of ≥45 days and ≥60 days and showed a lower hazard of discontinuation among patients initiating nebivolol than among patients initiating all other drug cohorts (p < 0.001). LIMITATIONS: Comparisons of non-randomized treatment groups may be confounded by unobserved differences in patients' baseline characteristics. CONCLUSIONS: Initiation with nebivolol was associated with greater persistence than initiation with atenolol, carvedilol, metoprolol, or other ß-blockers.

Clinical and economic outcomes of multiple versus single long-acting inhalers in COPD.

OBJECTIVE: To compare healthcare resource utilization and healthcare costs between COPD patients who used multiple long-acting inhalers versus those who used a single long-acting inhaler. METHODS: COPD patients meeting study inclusion criteria were identified in the Market Scan database (2004-2008) and were classified as being a multiple- or single-inhaler user. 11,747 multiple- and single-inhaler users were matched on baseline characteristics to balance disease severity. Patients were followed for 12 months. Incremental differences between the two groups were estimated for: number of exacerbations; time to first exacerbation; all-cause and COPD-related inpatient admissions, inpatient days, emergency room visits, urgent care visits, outpatient visits, and other medical services visits; all-cause and COPD-related healthcare costs. Multivariate regression analyses were also used to control for a number of potentially confounding factors. RESULTS: After controlling for a number of potentially confounding factors, multiple-inhaler users experienced significantly more exacerbations (0.52; p < .0001) and had a higher risk of exacerbation (HR = 1.40; p < .0001) than single-inhaler users. Multiple-inhaler users also incurred significantly more inpatient admissions (IRR = 1.15; p < .0001), inpatient days (IRR = 1.20; p < .0001), urgent care visits (IRR = 1.10; p = 0.0026), outpatient visits (IRR = 1.06; p < .0001), and other medical services visits (IRR = 1.12; p = <.001) than single-inhaler users, resulting in significantly higher all-cause health care costs ($3,319; p < .0001). Results of COPD-related resource use and costs were comparable. CONCLUSIONS: After controlling for a number of potentially confounding factors, multiple-inhaler users had more exacerbations, a higher risk of exacerbation, and higher healthcare resource utilization and costs compared to single-inhaler users.

Therapy persistence and adherence in patients with chronic obstructive pulmonary disease: multiple versus single long-acting maintenance inhalers.

OBJECTIVE: To compare persistence and adherence among patients with chronic obstructive pulmonary disease (COPD) treated with either multiple- or single- long-acting maintenance inhalers. METHODS: Patients with ≥2 COPD medical claims and ≥2 prescriptions for a long-acting inhaler within 1 year were classified as single- or multiple-inhaler users based on their treatment regimen (MarketScan database; 2004-2008) and matched on demographics and statistically significant baseline characteristics. Persistence, analyzed via time to treatment discontinuation, and treatment adherence, measured by proportion of days covered (PDC), were compared between the two groups over a 12-month period. Sensitivity analyses were conducted in patients with poorly and well-controlled disease. RESULTS: A total of 23,494 patients were grouped into 11,747 matched pairs. After adjusting for confounding factors, multiple-inhaler users had a significantly higher discontinuation rate [Hazard ratio = 1.40, p < 0.0001] compared with single-inhaler users. Multiple-inhaler users were less likely to be adherent than single-inhaler users with an average PDC of 0.51 (SD = 0.272) vs. 0.55 (SD = 0.279), respectively (p < 0.0001). These results were consistent for the poorly- and well-controlled disease groups. CONCLUSIONS: Multiple long-acting inhaler users demonstrated lower treatment persistence and adherence rates than single long-acting inhaler users. Limitations of the study are related to the retrospective, observational design and use of claims data.

Economic impact of therapeutic substitution of a brand selective serotonin reuptake inhibitor with an alternative generic selective serotonin reuptake inhibitor in patients with major depressive disorder.

BACKGROUND: To reduce pharmacy costs, managed care organizations encourage therapeutic substitution from brand to a generic product. However, little is known about whether these cost-containment strategies can also potentially lower total expenditures for payers in treatment of major depressive disorder (MDD). OBJECTIVE: To compare economic outcomes of patients with MDD who were switched from a brand selective serotonin reuptake inhibitor (SSRI) to an alternative generic SSRI for nonmedical reasons versus patients who continued on the brand SSRI. METHODS: Adult MDD patients in the Ingenix Impact Database (2003-2007) were considered "switchers" if they received treatment with a brand SSRI and were later switched to an alternative generic SSRI for nonmedical reasons. Patients who remained on the brand SSRI (nonswitchers) were matched 1:1 with switchers. All-cause, mental health-related, and MDD-related rates of hospitalizations/emergency department (ED) visits and costs over 6 months were compared both descriptively and by using adjusted regression models. A subgroup analysis on patients who were switched from escitalopram (Lexapro) to an alternative generic SSRI was also performed. RESULTS: The study included 4449 matched pairs. Compared with nonswitchers, switchers had higher risk of all-cause, mental health-related, and MDD-related use of hospitalizations/ED visits (OR 1.15, 1.34, and 1.54, respectively; all p < 0.01) and higher risk-adjusted mental health-related and MDD-related medical costs ($219 and $222, respectively; both p < 0.05). Subgroup analysis on escitalopram showed similar results; switchers experienced higher risk of any-cause, mental health-related, and MDD-related use of hospitalizations/ED visits (OR 1.21, 1.41, and 1.53, respectively; all p < 0.01) and higher risk-adjusted MDD-related medical costs ($151; p < 0.05). CONCLUSIONS: Compared with patients who continued on their patented SSRIs, patients who switched to a generic SSRI incurred more resource use of hospitalizations/ED visits and higher MDD-related health-care costs. The effects of therapeutic substitution should be carefully examined, because use of generic alternatives may not be a cost-saving strategy when total health-care costs are considered.

Cardiovascular and economic outcomes after initiation of atorvastatin versus simvastatin in an employed population stratified by cardiovascular risk.

The relative effects of atorvastatin and simvastatin among higher- and lower-risk patients are not well characterized. This study compared cardiovascular (CV) risk and direct and indirect costs among higher- and lower-risk employees initiating atorvastatin vs. simvastatin. Using a large employer claims database (1999-2006), employees were stratified as 1) high-risk employees with prior CV events, diabetes, or renal disorders; and 2) low- to intermediate-risk employees without these conditions. Propensity score matching was used, and 2-year outcomes were compared between matched cohorts. Indirect costs included disability payments and medically related absenteeism. Drug costs were imputed with recent prices to account for availability of generic simvastatin. Among 4167 matched pairs of high-risk employees, atorvastatin use was associated with a numerically lower risk of CV events (17.6 versus 18.4%, P = 0.37), higher direct medical costs ($17,590 versus $17,377, P = 0.002), numerically lower indirect costs ($4830 versus $4989, P = 0.29), and higher total costs by $54 ($22,420 versus $22,366, P = 0.034). The majority of high-risk employees (62%) received low initial statin doses (atorvastatin = 10 mg or simvastatin = 20 mg). Among 9326 matched pairs of low- to intermediate-risk employees, atorvastatin use was associated with a lower risk of CV events (3.1% versus 3.7%, P = 0.030), lower direct medical costs ($8400 versus $8436, P < 0.001), numerically lower indirect costs ($2781 versus $2807; P = 0.12), and lower total costs by $61 ($11,181 versus $11,243, P < 0.001). These results suggest that formulary policies reserving atorvastatin for higher-risk patients may not be cost-saving from the employer perspective.