Medication adherence, hospitalization, and healthcare resource utilization and costs in patients with pulmonary arterial hypertension treated with endothelin receptor antagonists or phosphodiesterase type-5 inhibitors.

Adherence to therapy for pulmonary arterial hypertension is essential to optimize patient outcomes, but data on real-world adherence to different pulmonary arterial hypertension drug classes are limited. This retrospective database analysis evaluated relationships between adherence, hospitalization, and healthcare costs in pulmonary arterial hypertension patients treated with endothelin receptor antagonists or phosphodiesterase type-5 inhibitors. From the IQVIA Adjudicated Health Plan Database, patients with pulmonary arterial hypertension were identified based on diagnostic codes and prescriptions for endothelin receptor antagonists (ambrisentan, bosentan, macitentan) or phosphodiesterase type-5 inhibitors (sildenafil, tadalafil) approved for pulmonary arterial hypertension. Patients were assigned to the class of their most recently initiated (index) pulmonary arterial hypertension therapy between 1 January 2009 and 30 June 2015. Medication adherence was measured by proportion of days covered; patients with proportion of days covered ≥80% were considered adherent. The proportion of adherent patients was higher for endothelin receptor antagonists (571/755; 75.6%) than for phosphodiesterase type-5 inhibitors (970/1578; 61.5%; P < 0.0001). In both groups, hospitalizations declined as proportion of days covered increased. Among adherent patients, those on endothelin receptor antagonists had a significantly lower hospitalization rate than those on phosphodiesterase type-5 inhibitors (23.1% versus 28.5%, P = 0. 0218), fewer hospitalizations (mean (standard deviation) 0.4 (0.8) versus 0.5 (0.9); P = 0.02), and mean hospitalization costs during the six-month post-index ($9510 versus $15,726, P = 0.0318). Increasing adherence reduced hospitalization risk more for endothelin receptor antagonists than for phosphodiesterase type-5 inhibitors (hazard ratio 0.176 versus 0.549, P = 0.001). Rates and numbers of rehospitalizations within 30 days post-discharge were similar between groups. Mean total costs were higher with endothelin receptor antagonists than phosphodiesterase type-5 inhibitors in all patients ($91,328 versus $72,401, P = 0.0003) and in adherent patients ($88,867 versus $56,300, P < 0.0001), driven by higher drug costs.

Estimation of Missed Statin Prescription Use in an Administrative Claims Dataset.

BACKGROUND: Nonadherence to statin medications is associated with increased risk of cardiovascular disease and poses a challenge to lipid management in patients who are at risk for atherosclerotic cardiovascular disease. Numerous studies have examined statin adherence based on administrative claims data; however, these data may underestimate statin use in patients who participate in generic drug discount programs or who have alternative coverage. OBJECTIVE: To estimate the proportion of patients with missing statin claims in a claims database and determine how missing claims affect commonly used utilization metrics. METHODS: This retrospective cohort study used pharmacy data from the PharMetrics Plus (P+) claims dataset linked to the IMS longitudinal pharmacy point-of-sale prescription database (LRx) from January 1, 2012, through December 31, 2014. Eligible patients were represented in the P+ and LRx datasets, had ≥1 claim for a statin (index claim) in either database, and had ≥ 24 months of continuous enrollment in P+. Patients were linked between P+ and LRx using a deterministic method. Duplicate claims between LRx and P+ were removed to produce a new dataset comprised of P+ claims augmented with LRx claims. Statin use was then compared between P+ and the augmented P+ dataset. Utilization metrics that were evaluated included percentage of patients with ≥ 1 missing statin claim over 12 months in P+; the number of patients misclassified as new users in P+; the number of patients misclassified as nonstatin users in P+; the change in 12-month medication possession ratio (MPR) and proportion of days covered (PDC) in P+; the comparison between P+ and LRx of classifications of statin treatment patterns (statin intensity and patients with treatment modifications); and the payment status for missing statin claims. RESULTS: Data from 965,785 patients with statin claims in P+ were analyzed (mean age 56.6 years; 57% male). In P+, 20.1% had ≥ 1 missing statin claim post-index; 13.7% were misclassified as nonstatin users; and 14.9% were misclassified as new statin users. MPR was higher in the augmented P+ dataset versus the P+ dataset alone for all patients (79.4% vs. 76.7%, P < 0.001) and new users (61.4% vs. 58.7%, P < 0.001). Similarly, mean PDC was higher in the P+ dataset augmented with LRx versus the P+ dataset alone for all patients (76.0% vs. 74.0%, P < 0.001) and new users (58.5% vs. 56.5%, P < 0.001). Most patients received moderate-intensity statins; few changes in dose, intensity, or discontinuation of statins were observed when the P+ dataset was augmented. The most common reasons for missing data were payment by an alternate third-party program (66.3%) and use of cash, coupon, or discount cards (18.7%). CONCLUSIONS: Augmenting commercial claims data with point-of-sale data provides a more accurate assessment of statin use than claims data alone. DISCLOSURES: This study was funded by Amgen, which contributed to data interpretation and manuscript preparation. Wade, Hill, and De are employees of QuintilesIMS, which received funding from Amgen for work on this study. Patel and Harrison are employees of Amgen and own Amgen stock/stock options. Study concept and design were contributed by Wade, Hill, Patel, and Harrison. De took the lead in data collection, along with the other authors, and all authors contributed to data analysis. The manuscript was written and revised by all the authors.

Improving Medication Adherence and Health Care Outcomes in a Commercial Population through a Community Pharmacy.

The aim was to evaluate the impact of a multifaceted set of medication management interventions offered by a community pharmacy on adherence, health care utilization, and costs within a commercial population. Patients initiating therapy within 16 drug classes from February 7, 2013, to October 6, 2013, were offered various adherence interventions by Walgreens pharmacy. Patients were linked deterministically to IMS medical and prescription databases for 6-month pre- and post-index data analysis. Walgreens patients (intervention) were matched to patients using other pharmacies (control) on drug class, index date, baseline demographics, clinical factors, utilization, and costs. Outcomes were evaluated at the intent-to-treat level using post-index differences and generalized estimating equations (GEE) regression model. Paired t tests (continuous variables) and McNemar's test (dichotomous variables) were used to determine the significance of estimated model coefficients at α = 0.05. The groups (n = 72,410 each) had similar age (47.1 vs. 45.7 years), sex (41.2% vs. 40.2% male), and disease burden (0.52 vs. 0.40 mean Charlson comorbidity index). In the 6-month post-index period, the intervention group had 3.0% greater medication adherence, 1.8% fewer hospital admissions, 2.7% fewer emergency room (ER) visits, and 0.53 fewer mean outpatient visits compared to the control group (all P < 0.0001). The intervention group incurred significantly lower GEE-adjusted pharmacy costs (-$92), outpatient costs (-$120), ER costs (-$38), and total health care costs (-$226.07) (all P < 0.0001), and higher inpatient costs ($86, P < 0.004) per patient. A multifaceted set of medication management interventions offered by a community pharmacy were associated with patients in a commercial population having significantly higher medication adherence and lower health care utilization and costs.

Treatment persistence among patients with rheumatoid disease (RA, AS, PsA) treated with subcutaneous biologics in Germany.

Patients with rheumatoid arthritis (RA), ankylosing spondylitis (AS), and psoriatic arthritis (PsA) are frequently treated with subcutaneous biologic therapies when disease progresses or when response to synthetic disease-modifying antirheumatic drugs (DMARDs) is inadequate. This study analyzed treatment persistence and treatment patterns for RA, AS, and PsA patients in Germany initiating subcutaneous biologic therapies with and without prior DMARDs use. A retrospective cohort study was conducted using the Electronic Medical Record database of IMS Disease Analyzer, Germany. Patients who were ≥18 years old; had at least one ICD-10 diagnosis code of RA, AS, or PsA during the study period; and had exposure to a subcutaneous biologic agent between January 1, 2009 and June 30, 2012 were selected. Patients were required to have continuous observation ≥12 months prior to and after index medication date. Persistence was defined as consecutive days from treatment initiation until treatment discontinuation (≥60-day lapse in medication coverage). Patients were stratified by pre-index use of DMARDs. Kaplan-Meier analysis was conducted to assess time to discontinuation, and logistic regression was conducted to identify characteristics associated with persistence. A total of 576 RA, 108 AS, and 197 PsA patients without biologic experience during the pre-index period were selected. The percentages of RA, AS, and PsA patients persistent ≥12 months were 51.9, 48.1, and 57.9 %, respectively. Median persistent time over 12 months was 365.0 days for RA (mean 245.9 days), 281.0 for AS (mean 228.5), and 365.0 for PsA (mean 264.1). In the RA cohort, a significantly higher proportion of those with pre-index DMARD use were persistent compared to those without pre-index DMARD (56.1 vs. 33.3 %, p = 0.0001). No significant differences were observed for the AS and PsA cohorts. Multivariate analyses confirmed that DMARD-experienced patients were 2.45 times more likely to be persistent with subcutaneous biologic therapy in the RA cohort. Switching between subcutaneous biologics occurred in <10 % of patients in all three cohorts. In the subpopulations with at least two prescriptions for the index subcutaneous biologic and who remained persistent on the index subcutaneous biologic, dose escalation of ≥50 % occurred in 50, 60, and 49 % in the RA, AS, and PsA cohorts, respectively. Among RA, AS, and PsA patients newly initiating subcutaneous biologic agents in Germany, persistence at 12 months is relatively low (48-58 %). For the RA cohort, patients with pre-index DMARD use are more persistent than patients without. The majority of patients do not switch between subcutaneous biologics. A notable proportion of patients who remained persistent on their index subcutaneous biologic had a dose escalation. There are opportunities to improve outcomes of patient with rheumatoid disease through improved medication persistence.

Anemia management trends in hospital-based dialysis centers (HBDCs), 2010 to 2013.

BACKGROUND: Few data have been reported on anemia management practices in hospital-based dialysis centers (HBDCs), which are uniquely different from other freestanding dialysis centers. Examining data from HBDCs would help determine if HBDCs and the general US dialysis population have similar trends related to how anemia is managed in dialysis patients. OBJECTIVE: Given recent changes in the prescribing information of erythropoiesis-stimulating agents (ESAs) and in end-stage renal disease-related health policy and reimbursement, this study describes trends in anemia management practices in HBDCs from January 2010 through March 2013. METHODS: Electronic medical records of 5404 adult hemodialysis patients in 50 US-based HBDCs were analyzed retrospectively. Patients included in the study cohort were aged ≥18 years and had at least 1 hemoglobin (Hb) measurement and 1 dose of an ESA between January 2010 and March 2013. End points included Hb concentration, darbepoetin alfa dosing, epoetin alfa dosing, and iron biomarkers (transferrin saturation and ferritin) and dosing. RESULTS: From 2010 to 2013, mean monthly Hb levels declined from 11.4 to 10.7 g/dL; the percentage of patients with mean monthly Hb levels <10 g/dL increased from 11.3% to 24.4%; and the percentage of patients with mean monthly Hb levels >12 g/dL declined from 30.1% to 11.2%. The median darbepoetin alfa cumulative 4-week dose also declined 38.8%, and the weekly epoetin alfa dose declined 24%. From January 2010 to March 2013, the percentage of patients with transferrin saturation >30% increased from 35.8% to 43.6%, the percentage of patients with ferritin levels >500 ng/mL increased from 62.0% to 77.9%, the percentage of patients with ferritin levels ≥800 ng/mL increased from 28.9% to 47.3%, and the median cumulative 4-week intravenous iron dose increased 50%. CONCLUSIONS: These study results support growing evidence that meaningful changes have occurred over the last 3 years in how anemia is clinically managed in US hemodialysis patients. Study limitations include that changes in patient clinical/demographic characteristics over time were not controlled for and that study findings may not be applicable to HBDCs that have different patient populations and/or do not use an electronic medical record system. Continuing to evaluate anemia management practices in HBDCs would provide additional information on the risks and benefits of anemia care. Consistent with national data, the findings from this study indicate that from 2010 to 2013, HBDCs modified anemia management practices for dialysis patients, as evidenced by reductions in mean monthly Hb levels and ESA dosing and by increases in iron biomarkers and dosing.

TSAT is a better predictor than ferritin of hemoglobin response to Epoetin alfa in US dialysis patients.

Clinical guidelines recommend concurrent treatment of anemia in end-stage renal disease with erythropoiesis-stimulating agents (ESAs) and iron. However, there are mixed data about optimal iron supplementation. To help address this gap, the relationship between iron markers and hemoglobin (Hb) response to ESA (Epoetin alfa) dose was examined. Electronic medical records of 1902 US chronic hemodialysis patients were analyzed over a 12-month period between June 2009 and June 2010. The analysis included patients who had at least one Hb value during each 4-week interval for four consecutive intervals (k - 2, k - 1, k, and k + 1; k is the index interval), received at least one ESA dose during intervals k - 1 or k, had at least one transferrin saturation (TSAT) value at interval k, and at least one ferritin value during intervals k - 2, k - 1, or k. Effect modification by TSAT and ferritin on Hb response was evaluated using the generalized estimating equations approach. Patients had a mean (standard deviation) age of 62 (15) years; 41% were Caucasian, 34% African American, 65% had hypertension, and 39% diabetes. Transferrin saturation, but not ferritin, had a statistically significant (P < 0.05) modifying effect on Hb response. Maximum Hb response was achieved when TSAT was 34%, with minimal incremental effect beyond these levels. Of the two standard clinical iron markers, TSAT should be used as the primary marker of the modifying effect of iron on Hb response to ESA. Long-term safety of iron use to improve Hb response to ESA warrants further study.

Synchronization of administrations of chemotherapy and erythropoiesis-stimulating agents and frequency of associated healthcare visits.

PURPOSE: The erythropoiesis-stimulating agents (ESAs), darbepoetin alfa (DA), and epoetin alfa (EA) differ with respect to dosing schedule in chemotherapy-induced anemia. DA can be administered less frequently than EA, which may increase synchronicity between chemotherapy and ESA schedules. This study compared DA and EA with respect to frequency of synchronization and frequencies of total and ESA healthcare visits in current clinical practice. METHODS: A retrospective analysis of ESA utilization during ESA episodes of care was conducted on all cancer patients identified in the SDI health oncology electronic medical records database who underwent chemotherapy and received ESA therapy from July 1, 2007 to March 31, 2010 (n = 6522 DA, n = 3,439 EA). RESULTS: The frequency of synchronization (chemotherapy and ESA therapy on the same day) was higher with DA (67 %) than EA (58 %) (p < 0.001). The odds that an ESA administration was synchronized with chemotherapy were higher with DA compared with EA (odds ratio = 1.46, 95 % CI: 1.37, 1.54). Compared with EA, DA patients had 2.3 fewer visits with an ESA administration (p < 0.001) and 3.0 fewer total visits (p < 0.001). CONCLUSIONS: Compared with patients receiving EA, DA patients were more likely to have an ESA administration on the same healthcare visit as chemotherapy and had fewer visits for any cause or for ESA administration. These results suggest that through greater synchronization of ESA and chemotherapy administrations, DA may reduce patient and practice burden and healthcare utilization.

The disease burden of pertussis in adults 50 years old and older in the United States: a retrospective study.

BACKGROUND: While the incidence of pertussis has increased in adolescents and adults in recent years in the U.S., little is known about the incidence and economic burden of pertussis in older adults. This study provides evidence of the incidence of pertussis and direct medical charges associated with pertussis episodes of care (PEOCs) in adults aged 50 years and older in the U.S. METHODS: PEOCs were divided into periods before and after the initial pertussis diagnosis was made (i.e., the index date) to capture any conditions immediately preceding the pertussis diagnosis that may have represented misdiagnoses and subsequent conditions that may have represented sequelae. Data were extracted from IMS's recently acquired SDI databases of longitudinal, patient-level practitioner claims and hospital operational billing records collected from private practitioners and hospitals, respectively, across the U.S. Patients 50 years and older with one or more ICD-9-CM diagnoses for pertussis/whooping cough and/or a laboratory test positive for Bordetella pertussis between 1/1/2006 and 10/31/2010 were eligible for study inclusion. Resource utilization and charges (i.e., unadjudicated claims) associated with the patient's physician and hospital care were analyzed. The nationally projected incidence of pertussis was estimated using a subsample of patients with the required data necessary for projection. RESULTS: Estimated incidence of diagnosed pertussis ranged from 2.1-4.6 cases per 100,000 people across the two age groups (50-64 and [greater than or equal to] 65) during the years 2006 to 2010. The analysis of charges included 5,748 patients [greater than or equal to] 50 years of age with pertussis. Average charges across the entire episode of care were $1,835 and $14,428 per patient in the outpatient and inpatient settings, respectively. The average number of outpatient (i.e., private practitioner) visits was 2 per patient in both the pre-index and post-index periods. CONCLUSIONS: In the U.S., the incidence of diagnosed pertussis in adults 50 years and older has increased between 2006 and 2010. Healthcare utilization and charges associated with pertussis are substantial, suggesting the need for additional prevention and control strategies and a higher degree of clinical awareness on the part of health care providers. Additional research regarding pertussis in older populations is needed to substantiate these findings.

Cost of palliative radiation to the bone for patients with bone metastases secondary to breast or prostate cancer.

BACKGROUND: To estimate the costs (paid amounts) of palliative radiation episodes of care (REOCs) to the bone for patients with bone metastases secondary to breast or prostate cancer. METHODS: Claims-linked medical records from patients at 98 cancer treatment centers in 16 US states were analyzed. Inclusion criteria included a primary neoplasm of breast or prostate cancer with a secondary neoplasm of bone metastases; ≥2 visits to ≥1 radiation center during the study period (1 July 2008 through 31 December 2009) on or after the metastatic cancer diagnosis date; radiation therapy to ≥1 bone site; and ≥1 complete REOC as evidenced by a >30-day gap pre- and post-radiation therapy. RESULTS: The total number of REOCs was 220 for 207 breast cancer patients and 233 for 213 prostate cancer patients. In the main analysis (which excluded records with unpopulated costs) the median number of fractions per a REOC for treatment of metastases was 10. Mean total radiation costs (i.e., radiation direct cost + cost of radiation-related procedures and visits) per REOC were $7457 for patients with breast cancer and $7553 for patients with prostate cancer. Results were consistent in sensitivity analyses excluding patients with unpopulated costs. CONCLUSIONS: In the US, current use of radiation therapy for bone metastases is relatively costly and the use of multi-fraction schedules remains prevalent.

Second-line treatment outcomes after first-line sunitinib therapy in metastatic renal cell carcinoma.

This study was conducted to evaluate the treatment outcomes associated with common second-line targeted therapies given after first-line sunitinib for metastatic renal cell carcinoma (mRCC). The sample comprised patients with mRCC (n = 257) who were receiving second-line everolimus, sorafenib, or temsirolimus between April 1, 2008, and February 29, 2011, after first-line sunitinib treatment. The patients were followed-up from the start of second-line treatment until treatment failure (defined as advancement to a third-line therapy or to mortality) or the last observation in the medical and pharmacy databases. Treatment failure was observed in 38.5% (n = 99) of cases: 20.2% of patients (n = 52) advanced a line of treatment; and 18.3% of patients (n = 47) died. Kaplan-Meier analysis indicated a statistical difference in time to treatment failure among the 3 second-line targeted therapies (log-rank test, P = .045). The estimated 1-year cumulative probabilities of treatment failure were 49.9% for everolimus, 68.4% for sorafenib, and 71.4% for temsirolimus. In a multivariate Cox proportional hazards model, a higher adjusted risk of treatment failure vs. everolimus was observed for both temsirolimus (hazard ratio [HR] 2.05 [95% CI, 1.26-3.35]; P = .004) and sorafenib (HR 1.77 [95% CI, 1.02-3.07]; P = .043). The results of this real-world data analysis suggest that the risk of second-line treatment failure after first-line sunitinib was significantly higher with temsirolimus and sorafenib compared with everolimus.

Clinical burden of illness in patients with neuroendocrine tumors.

OBJECTIVE: The objective of this study was to evaluate the incremental risk of morbidities affecting the cardiovascular, hepatic, gastrointestinal, skeletal, and neuropsychiatric systems in patients with neuroendocrine tumors (NETs) compared with a noncancer cohort. METHODS: In a retrospective, matched-control study using US claims databases, noncancer control subjects (n = 3524) were matched 2:1 with patients with newly diagnosed NET (n = 1762) on age, sex, region, hospital data availability, and index year. Rates of select morbidities were compared between patients with NET and control subjects. Incremental risks were analyzed using logistic regressions adjusting for baseline characteristics. RESULTS: In the first 3 years after diagnosis in patients with NET versus matched control subjects without cancer, (1) the adjusted risk of cardiovascular morbidities was higher (odds ratio [OR], 1.26; P = 0.0206); (2) the adjusted risk of hepatic or gastrointestinal morbidities was higher (OR, 1.95, P < 0.0001); (3) the adjusted risk of osteoporosis/osteopenia was higher among those 50 years or younger (OR, 3.24; P = 0.0081); and (4) the adjusted risk of anxiety/depression was higher among those 65 years or younger (OR, 1.48; P = 0.0210). CONCLUSIONS: Patients with NET have greater clinical burden of disease than matched control subjects with respect to conditions affecting the cardiovascular, hepatic, and gastrointestinal systems. Excess clinical burden of disease with respect to anxiety, depression, osteoporosis, and osteopenia was observed in patients with NET in the younger age groups.

Effect of reimbursement changes on erythropoiesis-stimulating agent utilization and transfusions.

Cancer patients frequently develop chemotherapy-induced anemia, which can be treated with erythropoiesis-stimulating agents. These agents have shifted the standard of chemotherapy-induced anemia treatment away from the previous mainstay of red blood cell transfusions. In July 2007, the Centers for Medicare and Medicaid Services issued a National Coverage Decision restricting reimbursement for erythropoiesis-stimulating agents to those chemotherapy patients who have hemoglobin levels <10 g/dL at initiation of therapy. This decision was hypothesized to place a greater reliance on transfusions for chemotherapy-induced anemia treatment. This observational study examined transfusions and erythropoiesis-stimulating agent utilization rates within defined episodes of chemotherapy care using electronic medical records from seven practices consisting of 39 sites of care across seven states. We compared the frequency of myelosuppressive chemotherapy treatment, erythropoiesis-stimulating agent administrations, and red blood cell transfusions before and after the National Coverage Decision in oncology patients with chemotherapy-induced anemia. Although exposure to myelosuppressive chemotherapy was not different, erythropoiesis-stimulating agent administrations significantly decreased and blood transfusions significantly increased after implementation of the National Coverage Decision. The 31% increase in transfusions for patients aged 65 years and older was significant (P = 0.007) and higher than the 8% increase for patients younger than 65 years (P = 0.358). Changes in practice patterns for chemotherapy-induced anemia treatment that followed the Centers for Medicare and Medicaid Services reimbursement decision for erythropoiesis-stimulating agents seem to be impacting practice patterns. Further research is necessary to determine whether these changes represent a widespread and durable shift in patient treatment.

Comparative antibiotic failure rates in the treatment of community-acquired pneumonia: Results from a claims analysis.

INTRODUCTION: Antibiotic treatment failure contributes to the economic and humanistic burdens of community-acquired pneumonia (CAP) by increasing morbidity, mortality, and healthcare costs. This study compared treatment failure rates of levofloxacin with those of other antibiotics in a large US sample. METHODS: Medical and pharmacy claims in the nationally representative SDI database were used to identify adults with a new outpatient diagnosis of CAP receiving a study antibiotic (levofloxacin, amoxicillin/clavulanate, azithromycin, moxifloxacin) between September 1, 2005 and March 31, 2008. Treatment failure was defined as ≥1 of the following events ≤30 days after index date: a refill for the index antibiotic after completed days of therapy, a different antibiotic dispensed >1 day after the index prescription, or hospitalization with a pneumonia diagnosis or emergency department visit >3 days postindex. Cohorts were propensity score matched for demographic and clinical characteristics. Treatment failure rates were compared between pairs of cohorts for the full sample and for high-risk patients (age ≥65 and/or on Medicaid). RESULTS: Among the 3994 study patients, the numbers of dispensed index prescriptions were 268 for amoxicillin/clavulanate, 1609 for azithromycin, 1460 for levofloxacin, and 657 for moxifloxacin. Unadjusted treatment failure rates for the sample were 20.8% for levofloxacin, 23.9% for amoxicillin/clavulanate, 23.9% for azithromycin, and 19.9% for moxifloxacin. For high-risk patients, unadjusted treatment failure rates were 19.1% for levofloxacin, 26.1% for amoxicillin/clavulanate, 26.3% for azithromycin, and 24.3% for moxifloxacin. Propensity score-matched treatment failure rates were significantly lower with levofloxacin than azithromycin (19.8% vs. 24.5%, odds ratio [OR] comparator vs. levofloxacin 1.38; 95% CI: 1.14, 1.67), a difference amplified in high-risk patients (19.0% vs. 26.4%, OR 1.61; 95% CI: 1.22, 2.13). No significant differences were observed for other paired comparisons. CONCLUSION: In a large US sample, treatment failure in CAP appeared to be less likely with quinolones (such as levofloxacin) than azithromycin, an effect particularly marked in high-risk patients (age ≥65 and/or on Medicaid).

Switching from atorvastatin to simvastatin in patients at high cardiovascular risk: effects on low-density lipoprotein cholesterol.

Since generic simvastatin became available in the United States in 2006, approximately one million patients have switched from atorvastatin to simvastatin. We examined the association between switching from atorvastatin to simvastatin and changes in low-density lipoprotein cholesterol (LDL-C) levels in clinical practice. We compared atorvastatin-treated patients at high cardiovascular risk who switched to simvastatin between June 2006 and July 2007 with randomly selected matched patients who remained on atorvastatin and evaluated changes in LDL-C and percentage of patients reaching LDL-C less than 100 mg/dL. Of patients who switched from atorvastatin to simvastatin, the majority were excluded as a result of lack of LDL-C measurements, leaving 383 patients in the analysis. Among these, 122 (31.9%) switched to a simvastatin dose that was less than therapeutically equivalent to their prior atorvastatin dose. Compared with control subjects, switched patients were less likely to reach an LDL-C less than 100 mg/dL (68.4% versus 74.0%; odds ratio, 0.76; 95% confidence interval, 0.59-0.99; P = 0.041) and had higher measured LDL-C (91.4 versus 87.2 mg/dL; P = 0.009). Switched patients who were not prescribed a higher milligram dose of simvastatin were significantly less likely to reach an LDL-C less than 100 mg/dL (62.3% versus 74.0%; odds ratio, 0.55; 95% confidence interval, 0.36-0.84; P = 0.006) and had higher LDL-C (95.1 versus 87.2 mg/dL; P = 0.002) than control subjects. A large proportion of patients who switch from atorvastatin to simvastatin are prescribed doses that are not therapeutically equivalent, and these patients were significantly less likely to meet LDL-C treatment goals compared with patients who remained on atorvastatin.

The importance of clinical variables in comparative analyses using propensity-score matching: the case of ESA costs for the treatment of chemotherapy-induced anaemia.

BACKGROUND: The erythropoiesis-stimulating agents (ESAs) epoetin alfa (EA) and darbepoetin alfa (DA) have comparable efficacy in treating chemotherapy-induced anaemia (CIA). Therapy choice depends on many factors, including cost. Previous estimates of ESA cost differences have been derived from claims data. These data lack clinical variables, such as baseline haemoglobin (Hb) level, which are likely to influence choice of ESA, dosing and costs. We estimated cost differences between DA and EA in patients with cancer receiving chemotherapy, using a propensity-score matched analysis of baseline patient characteristics with and without Hb values to assess the effect of this clinical variable on ESA cost estimates. METHODS: Data were extracted from electronic medical records in two US databases between January 2004 and December 2006. The study sample included 6743 patients receiving chemotherapy, with one or more visits during the study period, who received an ESA during a chemotherapy episode. Episodes of chemotherapy care were constructed using a 90-day gap in administration to identify the start and end. Patients receiving both DA and EA during their initial chemotherapy episode or with missing data were excluded, representing 42% of patients with CIA receiving an ESA. Drug costs were calculated from the cumulative dose multiplied by 106% of the average sales price (ASP) for DA or EA. Two propensity-score matches were conducted: first using variables available in administrative billing claims systems, then adding the baseline Hb test result. Regression-adjusted cost differences were estimated with and without baseline Hb, using generalized linear models. RESULTS: Using baseline Hb levels resulted in a better match of the baseline characteristics for the EA and DA treatment groups than the original sample or the matched sample without Hb variables. Mean ESA costs (year 2007 values) for the original sample were $US4171 for EA and $US3811 for DA (mean difference $US360; p < 0.001, standard error [SE] $US99). With propensity-score matching without Hb variables, mean estimated costs were $US3836 for EA and $US3599 for DA (mean difference $US237; p = 0.053, SE $US123). With propensity-score match including Hb variables, mean costs were $US3965 for EA and $US3536 for DA (mean difference $US429; p = 0.001, SE $US125). Cost differences in sensitivity analyses ranged between $US102 (p = 0.201) and $US261 (p = 0.003). CONCLUSIONS: Addition of baseline Hb level as a variable in propensity score and ESA cost models affects ESA treatment cost estimates in patients with cancer receiving chemotherapy. Cost comparisons based on observational data should use analytical methods that account for differences in clinical variables between treatment groups.

Effects of angiotensin-converting enzyme inhibitor or angiotensin receptor blocker therapy after hospital discharge on subsequent rehospitalization for acute myocardial infarction and heart failure.

American College of Cardiology/American Heart Association guidelines recommend angiotensin-converting enzyme inhibitor (ACEI) or angiotensin receptor blocker (ARB) therapy following acute myocardial infarction (MI) or development of heart failure (HF). This study estimated the effects of initiating these therapies after hospitalization for MI or HF on subsequent 1-year rehospitalization rates for MI or HF. A retrospective multivariate analysis of medical claims for 14,327 patients receiving and 7905 not receiving an ACEI or ARB after discharge for MI or HF was conducted. Rehospitalization for MI or HF was lower for treated vs untreated patients (MI: odds ratio [OR]=0.53, P<.001; HF: OR=0.52, P<.001). Rehospitalization was lower in treated patients with high medication compliance (medication possession ratio [MPR]>80%) and medium compliance (MPR 40%-79%) vs patients with low compliance (ORs for MI: high=0.54, medium=0.69; P<.001); ORs for HF: high=0.38, medium=0.62; P<.001). In conclusion, ACEI or ARB therapy initiated after hospitalization for MI or HF reduced risk of rehospitalization, and greater risk reduction was achieved with higher medication compliance.

Impact of a geriatric case management program on health plan costs.

We evaluated the impact of HIP, Health Plan of New York's geriatric case management (GCM) program, which is offered to Medicare Advantage members at high risk for high health care costs and utilization. The study design was a comparison of health plan costs for program participants and nonparticipants eligible for the program, controlling for variables predictive of high health care costs measured prior to program enrollment. The GCM program's impact on health care cost was derived from regression models comparing the costs of 101 program participants without exposure to other disease management programs to 1585 eligible nonparticipants, controlling for age, sex, and health care costs in the pre-program period. Net costs or savings from the program were computed as the sum program operation costs and the estimated change in health care costs associated with program participation. Mean annual health care costs for each program participant were $7720 lower than for eligible nonparticipants (P = .0090). The lower health care costs were attributable to the lower costs for inpatient and outpatient hospital and skilled nursing facility settings, exceeding the higher costs for physician office visits and prescription drugs. Estimated program costs were $2755 per member managed by the program, yielding a net savings of $4965 per member enrolled. A GCM program was successfully implemented in a large Medicare Advantage program. The reductions in health care costs achieved through GCM exceeded program costs resulted in meaningful savings for the health plan.

Utilization of darbepoetin alfa in relation to cancer patients' hemoglobin levels.

OBJECTIVE: Previous labeling and guidelines recommended initiating erythropoiesis agents (ESAs) for chemotherapy-induced anemia (CIA) at hemoglobin (Hb) levels < 11 g/dL, maintaining near 12 g/dL, and withholding at > or = 13 g/dL. This study analyzed adherence with recommendations in administration of darbepoetin (DA) to cancer patients. DESIGN, SETTING, AND PARTICIPANTS: Retrospective analysis of Hb levels at which DA was administered using Varian electronic medical records (EMRs). The dataset comprises 141 694 cancer patients from 82 sites across 13 states. The study evaluated DA administrations with respect to recorded Hb for 8988 patients from 1/1/05 to 5/31/07. MAIN OUTCOME MEASURES: Proportion of DA administrations at Hb > or = 12 and Hb > or = 13 g/dL. Hb level was analyzed for all administrations, stratified by year and anemia type (CIA, anemia-of-cancer, and myelodysplastic syndrome). RESULTS: There were 51 111 DA administrations with Hb results. The proportion of administrations at Hb > or = 12 g/dL was 7.2% and at Hb > or = 13 g/dL was 0.6%, and for CIA 6.9%/0.6%, anemia of cancer (AOC) 8.8%/0.8%, and myelodysplastic syndrome (MDS) 6.5%/0.6%. The proportion of all DA administrations at Hb > or = 12 g/dL and > or = 13 g/dL declined from 8.6% to 5.3% (p < 0.0001) and from 0.7% to 0.4% (p < 0.0007), respectively during 1/1/05-5/31/07. CONCLUSIONS: In this population, DA administration at Hb > or = 12 g/dL and Hb > or = 13 g/dL occurred in 7.2% and 0.6% of administrations, respectively, a approximately 93% adherence rate with recommendations. Further research is required to understand dose titrations at Hb 12-13 g/dL, and whether similar patterns are observed for other ESAs, and in other practice settings. This study provides context for the debate regarding the utilization, benefits and risks of ESAs in cancer patients.

Medication Utilization Patterns and Hypertension-Related Expenditures among Patients Who Were Switched from Fixed-Dose To Free-Combination Antihypertensive Therapy.

Using a retrospective cohort study of medical and pharmacy claims data, we evaluated medication compliance, persistence, and hypertension-related expenditures among patients who were switched from fixed-dose combination (FDC) to free-combination (FC) antihypertensive therapy. An example of a fixed-dose combination product for hypertension would be a valsartan/HCT tablet, and a free-combination product would be a valsartan tablet plus a diuretic tablet.The 7,224 patients identified from January 2003 to December 2005 were matched, in a 1:1 ratio, by propensity scores to controls who remained on their FC antihypertensive medications. Compliance, defined as a medication-possession ratio, was measured over 12 months. Persistence was measured as the percentage of patients who did not experience a lapse in therapy of more than 30 days since their last prescription refill.The patients continuing with FDC therapy had better persistence (42.5% higher; P < 0.002) and compliance (22.1% higher; P < 0.001), compared with patients who were switched to FC therapy. The 22.1% higher compliance rate for patients continuing the FDC regimen was associated with significantly lower expenditures for hypertension-related health care (P < 0.001) and an estimated 5% reduction in hypertension-related expenditures.

Therapeutic dose assessment of patient switching from atorvastatin to simvastatin.

OBJECTIVE: Patient switching of prescription drug brands within a therapeutic class has become more prevalent with tiered drug plan formularies. Although switching from more expensive brand name drugs to generic equivalents may reduce aggregate prescription costs, therapeutic benefit may be compromised if the patient is not switched to a drug with an equivalent therapeutic profile. This study examined whether patients switching from branded atorvastatin to either a branded or generic simvastatin were prescribed a therapeutically equivalent or higher dose, as opposed to a lower therapeutic dose. METHODS: Study patients were selected from a national longitudinal database of 1.4 billion annual prescription drug claims. All patients active in the database during the study period (9/01/2005 to 9/30/2006) with a prescription drug claim for atorvastatin in the index month (9/2005) were selected. The 453,409 patients in the study period were followed for 12 months to determine the percent switching to simvastatin and their relative therapeutic doses after switching. Patients switching to the same or lower milligram dose of simvastatin were classified as receiving a lower therapeutic dose compared with their atorvastatin dosing. RESULTS: Among patients using atorvastatin at the beginning of the study, 13,530 (3%) switched to simvastatin by the end of the study period. Medication changes resulted in a lower therapeutic dose in 38% of the switches. The percent of switches resulting in a lower therapeutic dose were 18% for those switching from 10 mg, 43% for those switching from 20 mg, 73% for those switching from 40 mg, and 100% for those switching from 80 mg. CONCLUSIONS: A significant proportion of patients switching from atorvastatin to simvastatin received a lower therapeutic dose, which may have an adverse impact on patients' quality of care and health status. Further research is needed to assess the potential negative effect on patient outcomes.