Healthcare Resource Use, Costs, and Disease Progression Associated with Diabetic Nephropathy in Adults with Type 2 Diabetes: A Retrospective Observational Study.

INTRODUCTION: Diabetic nephropathy (DN) is a progressive kidney disease resulting as a complication of diabetes mellitus. This study evaluated the disease progression and economic burden of DN among commercially insured patients with type 2 diabetes in the USA. METHODS: The research design was a retrospective observational study based on healthcare claims data. The Truven MarketScan Databases (2004-2014) were queried for adults with type 2 diabetes with at least one urine albumin test (index, randomly selected) after diagnosis and at least one test after the index. On the basis of the index test, patients were classified into normoalbuminuria, microalbuminuria, or macroalbuminuria groups. Nephropathy-related treatment use was measured in the 6 months after the index, disease progression was assessed from the index to the end of data availability, and annual all-cause and nephropathy-related costs and healthcare resource use (HRU) were assessed up to 2 years from the index. Outcomes were compared between any two groups, controlling for baseline demographics. RESULTS: A total of 23,235 patients were identified and classified into normoalbuminuria (N = 18,409), microalbuminuria (N = 3863), or macroalbuminuria (N = 963) groups. Patients with albuminuria were more likely to be older, male, and have a higher burden of baseline comorbidities and HRU. Within 6 months following the index, 12-20% of patients with albuminuria were not treated with any relevant recommended treatment. Compared to the normoalbuminuria group, patients with macroalbuminuria had a significantly greater risk of disease progression (hazard ratio [HR] = 1.44), and both albuminuria groups were more likely to require dialysis (HR = 4.23 and 40.14 for micro- and macroalbuminuria, respectively; all p < 0.05). Annual all-cause (2016 US dollars, $3580 and $12,830 higher for micro- and macroalbuminuria vs. normoalbuminuria, respectively) and nephropathy-related ($362 and $3716) costs increased significantly with increasing nephropathy severity, consistent with the trend in increased HRU. CONCLUSIONS: Diabetic nephropathy may be undertreated or inappropriately treated. It was also associated with significantly higher costs, HRU, and risk of disease progression among commercially insured patients with type 2 diabetes in the USA. FUNDING: Takeda Development Center Americas, Inc.

Evaluation of patients with type 2 diabetes mellitus receiving treatment during the pre-diabetes period: Is early treatment associated with improved outcomes?

AIM: This study evaluates the association of pretreatment with oral antidiabetics (OADs) on clinical outcomes and health resource utilization among commercially insured type II diabetes mellitus (T2DM) patients in the United States. METHODS: Using administrative data (Truven MarketScan® Research Databases), patients diagnosed with T2DM between 2007 and 2014 with ⩾6months continuous enrolment pre- and post-diagnosis were evaluated. Pretreatment was defined as OAD use at least 3months prior to T2DM diagnosis. Time-to-insulin initiation and healthcare costs were compared by OAD pretreatment status. RESULTS: Of the 866,605 patients studied, 241,856 (27.9%) were pretreated prior to T2DM diagnosis. Mean follow-up was 2.9years for pretreatment and 3.1years for those without pretreatment. Monthly diabetes-related pharmacy costs were significantly higher among pretreated patients ($66 versus $36, p<0.0001), as were overall monthly pharmacy costs ($255 versus $198, p<0.0001). Pretreated patients had lower mean monthly costs, both total ($625 versus $671, p<0.0001) and diabetes-related ($207 versus $214, p=0.0012). After multivariable adjustment, mean monthly diabetes-related total healthcare costs were higher among pretreated patients (+$60) but total all-cause monthly healthcare costs were significantly lower (-$354) (both p<0.05). Pretreatment was associated with a lower insulin initiation probability for 2years, after which probability was similar; the adjusted hazard ratio for pretreatment in a time-to-insulin model was 0.96 (95% CI, 0.94-0.97). CONCLUSIONS: Pretreatment with OADs is associated with a modest delay in initiating insulin therapy and lower total healthcare costs. The clinical and pharmacoeconomic benefits of pretreatment should be elucidated in a prospective study.

Validation of a Patient-reported Outcome (PRO) Measure and a Clinician-reported Outcome (CRO) Measure to Assess Satisfaction with Pharmacologic Stress Agents for Single-photon Emission Computed Tomography (SPECT) Myocardial Perfusion Imaging (MPI).

PURPOSE: The objective of this study was to develop and validate clinician and patient measures of satisfaction for pharmacologic stress agents (PSAs) used in single-photon emission computed tomography myocardial perfusion imaging procedures. METHODS: Two questionnaires were developed: the Clinician Satisfaction and Preference Questionnaire (CSPQ) and the Patient Satisfaction and Preference Questionnaire (PSPQ). Items were developed, and the content validity of the questionnaires was ensured by participants' involvement in the item generation (5 clinician and 18 patient face-to-face concept elicitation interviews) and item modification phases (5 clinician and 10 patient face-to-face cognitive debriefing interviews). Psychometric validation of the satisfaction component of the questionnaires was conducted in a sample of 9 clinicians and 90 patients. FINDINGS: After initial patient interviews and cognitive interviews, two 8-item instruments were developed with each containing an optional PSA preference question. The PSPQ assessed patients' receptiveness and satisfaction with the PSA that they received. The CSPQ assessed clinicians' satisfaction with the time and ease of PSA preparation, administration, and monitoring of the PSA. The optional preference question in both instruments assesses preference among PSAs. In a multicenter observational study of 88 patients and 9 clinicians, the PSPQ Preparation and Reaction to Agent scales elicited reliability coefficients of 0.90 and 0.87, respectively. In addition, the test-retest reliability was acceptable for all PSPQ scales (intraclass correlation coefficient range, 0.73-0.86). Concurrent validity with the Treatment Satisfaction Questionnaire for Medication (TSQM) indicates low-to-moderate correlations between the Effectiveness, Convenience, and Global Satisfaction scales of the TSQM with the PSPQ Satisfaction with Administration, Satisfaction with Effects, and Overall Satisfaction items (range, 0.46-0.78). Analysis of the CSPQ found that both the Preparation and Reaction to Agent subscales indicated strong internal consistency (α = 0.98 and 0.99, respectively). IMPLICATIONS: The PSPQ and CSPQ were developed and validated with rigorous methods. The instruments and their domains found strong internal consistency and good test-retest reliability. These questionnaires, when used as measures of treatment satisfaction in clinical trials, real-world observational studies, or by clinicians in their own laboratories, may help patients and clinicians better understand the impact of single-photon emission computed tomography myocardial perfusion imaging pharmacologic stress testing.

Relationship of fluconazole prophylaxis with fungal microbiology in hospitalized intra-abdominal surgery patients: a descriptive cohort study.

INTRODUCTION: Historically, Candida albicans has represented the most common cause of candidemia. However, the proportion of bloodstream infections due to non-albicans Candida species has increased. Because of the risk for candidemia in intra-abdominal surgical patients, some experts advocate the use of fluconazole prophylaxis. The impact of this practice on the distribution of Candida species isolated in breakthrough fungal infections in this population is unknown. We examined the association of fluconazole prophylaxis with the distribution of Candida species in intra-abdominal surgery patients. METHODS: We retrospectively identified cases with a positive blood culture (BCx) for Candida among hospitalized adult intra-abdominal surgery patients between July 2005 and October 2012. Distribution of Candida species isolated represented our primary endpoint. Qualifying surgical cases were determined based on a review of discharge International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) codes. Patients receiving low-dose fluconazole prior to the positive BCx with a known indication for prophylaxis including neutropenia, ICU exposure or history of organ transplantation were classified as prophylaxis. Appropriateness of fungal treatment was determined by the timing and selection of antifungal agent based on fungal isolate. RESULTS: Among 10,839 intra-abdominal surgery patients, 227 had candidemia. The most common Candida species isolated was C. albicans (n = 90, 39.6%) followed by C. glabrata (n = 81, 35.7%) and C. parapsilosis (n = 38, 16.7%). Non-albicans Candida accounted for 57.7% of isolates among the 194 non-prophylaxis patients and 75.8% among the 33 prophylaxis patients (P = 0.001). C. glabrata, the most common non-C. albicans species, was more prevalent than C. albicans in persons given prophylaxis, but not in those without prophylaxis. A total of 63% of those with candidemia were treated inappropriately based on the timing and selection of antifungal administration. CONCLUSIONS: Selection pressure from fluconazole prophylaxis in at-risk surgical patients may be associated with a drift toward fluconazole-resistant species in subsequent candidemia. Tools are needed to guide appropriate treatment through the prompt recognition and characterization of candidemia.

Hospital days, hospitalization costs, and inpatient mortality among patients with mucormycosis: a retrospective analysis of US hospital discharge data.

BACKGROUND: Mucormycosis is a rare and potentially fatal fungal infection occurring primarily in severely immunosuppressed patients. Because it is so rare, reports in the literature are mainly limited to case reports or small case series. The aim of this study was to evaluate inpatient mortality, length of stay (LOS), and costs among a matched sample of high-risk patients with and without mucormycosis in a large nationally representative database. METHODS: We conducted a retrospective analysis using the 2003-2010 Healthcare Cost and Utilization Project - Nationwide Inpatient Sample (HCUP-NIS). The NIS is a nationally representative 20% sample of hospitalizations from acute care United States (US) hospitals, with survey weights available to compute national estimates. We classified hospitalizations into four mutually exclusive risk categories for mucormycosis: A- severely immunocompromised, B- critically ill, C- mildly/moderately immunocompromised, D- major surgery or pneumonia. Mucormycosis hospitalizations ("cases") were identified by ICD-9-CM code 117.7. Non-mucormycosis hospitalizations ("non-cases") were propensity-score matched to cases 3:1. We examined demographics, clinical characteristics, and hospital outcomes (mortality, LOS, costs). Weighted results were reported. RESULTS: From 319,366,817 total hospitalizations, 5,346 cases were matched to 15,999 non-cases. Cases and non-cases did not differ significantly in age (49.6 vs. 49.7 years), female sex (40.5% vs. 41.0%), White race (53.3% vs. 55.9%) or high-risk group (A-49.1% vs. 49.0%, B-20.0% vs. 21.8%, C-25.5% vs. 23.8%, D-5.5% vs. 5.4%). Cases experienced significantly higher mortality (22.1% vs. 4.4%, P<0.001), with mean LOS and total costs more than 3-fold higher (24.5 vs. 8.0 days and $90,272 vs. $25,746; both P<0.001). CONCLUSIONS: In a national hospital database, hospitalizations with mucormycosis had significantly higher inpatient mortality, LOS, and hospital costs than matched hospitalizations without mucormycosis. Findings suggest that interventions to prevent or more effectively treat mucormycosis are needed.

Budget impact analysis of liposomal amphotericin B and amphotericin B lipid complex in the treatment of invasive fungal infections in the United States.

BACKGROUND: Liposomal amphotericin B (L-AMB) and amphotericin B lipid complex (ABLC) are both indicated for treating invasive fungal infections (IFIs) caused by Aspergillus, Candida and Cryptococcus spp. among patients who are refractory to or intolerant of conventional amphotericin B (CAB). Prior studies have suggested similar efficacies but differences in adverse event (AE) profiles between L-AMB and ABLC. OBJECTIVE: Our objective was to conduct a cost-minimisation and budget impact analysis for the treatment of IFIs with L-AMB and ABLC in a US hospital setting. METHODS: A Microsoft® Excel-based budget impact model was developed to estimate the costs associated with using L-AMB and ABLC for the treatment of adult patients with Aspergillus, Candida and Cryptococcus spp. infections, who are refractory to or intolerant of CAB, during a hospital stay. The model was built from a hospital perspective, and included drug costs of L-AMB and ABLC, and costs for treating drug-related AEs (i.e. nephrotoxicity with/without dialysis, infusion-related reactions, anaphylaxis, hypomagnesaemia and hypokalaemia). Average sales price was used as the drug cost estimate in the base-case analyses. The treatment duration and rates of AEs for L-AMB and ABLC were mainly obtained from a retrospective study of these two drugs in the target population using the Cerner Health Facts data. Treatment costs of AEs were obtained from the publicly available sources. The budget impact ($US, year 2011 values) was evaluated for a hypothetical hospital with 100 administrations where L-AMB and ABLC are used for the treatment of the target population by changing the market share of L-AMB and ABLC from 32/68% to an anticipated market share of 60/40% in the base-case analysis. Sensitivity analyses were conducted by varying drug costs, rates of AEs, costs of AEs and anticipated market shares of L-AMB and ABLC. RESULTS: The estimated per-patient cost per hospital episode associated with L-AMB and ABLC use were $US14,563 and $US16,748, respectively. Cost of AEs accounted for 68.7% of the costs for L-AMB and 85.4% for ABLC. In a hypothetical hospital with 100 annual admissions of patients using these two drugs for IFIs, changing the market shares from 32/68% for L-AMB and ABLC, respectively, to 60/40% yielded a 3.8% cost reduction, which corresponded to an absolute cost savings of $US61,191. Sensitivity analyses indicated that the results were robust to changes in input parameter values in most cases. CONCLUSIONS: This study suggests that hospitals can realize cost savings by substituting L-AMB for ABLC in the treatment of IFIs. The cost savings are driven by the lower rates of AEs associated with L-AMB use compared with ABLC.

Outcomes associated with conventional versus lipid-based formulations of amphotericin B in propensity-matched groups.

BACKGROUND: Lipid-based formulations of amphotericin B (LF-AMB) are indicated for treatment of invasive fungal infections in patients intolerant to conventional amphotericin B (CAB) or with refractory infections. Physicians still may choose to administer CAB to such patients. We described the use of CAB and LF-AMB in this population and quantified differences in post-amphotericin B length of stay (LOS) among survivors and hospital mortality in matched patients. METHODS: Data were extracted from Health Facts (Cerner Corporation, Kansas City, MO, USA) for a retrospective cohort analysis. Inpatients aged ≥18 years with evidence of fungal infection and with orders for LF-AMB or CAB on ≥2 days from January 2001 to June 2010 were identified. Patients were required to have renal insufficiency or other relative contraindications to use of CAB, exposure to nephrotoxic agents, or evidence of a CAB-refractory infection. Multilevel (hierarchical) mixed-effects logistic regression was used to determine factors associated with initial exposure to LF-AMB versus CAB. Multivariate adjustment of outcomes was done using propensity score matching. RESULTS: 655 patients were identified: 322 patients initiated therapy with CAB and 333 initiated treatment with LF-AMB. Compared to those initiating CAB, patients initiating LF-AMB had greater acuity and underlying disease severity. In unadjusted analyses, hospital mortality was significantly higher in the LF-AMB group (32.2% versus 23.7%; P = 0.02). After propensity score matching and covariate adjustment, mortality equalized and observed differences in LOS after amphotericin B initiation decreased. CONCLUSION: Among patients at risk for amphotericin B toxicity, differences between CAB and LF-AMB seen in crude outcomes analyses relate to channeling of sicker patients to initiate treatment with LF-AMB. Failing to account for differences among patients that drive clinical decision-making will result in inaccurate conclusions about the real-world effectiveness of different amphotericin B formulations.

Comparison of adverse events and hospital length of stay associated with various amphotericin B formulations: sequential conventional amphotericin b/lipid versus lipid-only therapy for the treatment of invasive fungal infections in hospitalized patients.

PURPOSE: Patients with invasive fungal infections are often treated initially with conventional amphotericin B deoxycholate (CAB), followed by a switch to lipid-based formulations of amphotericin B (LF-AMB). Our study examined adverse events and hospital length of stay (LOS) among adults who received LF-AMB exclusively or CAB followed by LF-AMB (CAB/LF-AMB). METHODS: Data were extracted from the Cerner Health Facts database. The study included adults with evidence of infection by Aspergillus, Candida, or Cryptococcus in addition to either renal insufficiency, a clinical condition suggesting intolerance to CAB, or CAB exposure within 90 days of admission. Nephrotoxicity was defined as a serum creatinine (SCr) level exceeding a 100% increase from baseline and an absolute level above 1.2 mg/dL. We used a hierarchical mixed-effect logistic regression model with nephrotoxicity as the outcome for the multivariate analysis. RESULTS: The study included 327 LF-AMB and 81 CAB/LF-AMB patients with similar demographics and baseline SCr values. The mean pre-to-post percentage increase in SCr levels was greater for CAB/LF-AMB (122.9%) compared with LF-AMB (62.2%) (P < 0.001). The multivariate-adjusted odds ratio of nephrotoxicity was 5.93, for a 95% confidence interval of 2.92 to 12.05 (P < 0.001) for CAB/LF-AMB compared with LF-AMB. Hypokalemia, hypomagnesemia, and infusion-related reactions were more frequent with CAB/LF-AMB. Compared with the LF-AMB group, the CAB/LF-AMB patients had a longer post-amphotericin B LOS (24.1 days vs. 15.7 days, respectively; P < 0.001), with a marginal effect of 4.5 days longer for those receiving CAB/LF-AMB (P = 0.016). CONCLUSION: In this retrospective study, we noted a significantly longer post-amphotericin B LOS and a greater frequency of adverse events, including nephrotoxicity, for patients whose initial treatment was CAB and who were switched to LF-AMB, compared with patients who received LF-AMB only.

Nephrotoxicity and other adverse events among inpatients receiving liposomal amphotericin B or amphotericin B lipid complex.

Nephrotoxicity evaluations between liposomal amphotericin B (L-AMB) and amphotericin B lipid complex (ABLC) have provided mixed results. This retrospective study used an electronic medical record database of hospitalized patients with invasive fungal infections treated with either L-AMB or ABLC. Patients had renal insufficiency, clinical condition suggesting intolerance to amphotericin B deoxycholate (CAB), or recent CAB exposure. Baseline SCr, exposure to other nephrotoxic agents, and total amphotericin B exposure were similar between the groups. In 105 patients administered L-AMB, 10.6% had nephrotoxicity versus 22.6% of 222 patients administered ABLC (P = 0.020). A logistic regression model found ABLC patients had 3.48 higher odds (95% CI 1.05-11.52) than L-AMB of developing nephrotoxicity. Infusion reactions were more prevalent with ABLC (23.9% versus 9.5%, P = 0.002) as was hypomagnesemia (44.3% versus 28.1%, P = 0.033). This study demonstrated that L-AMB is associated with less nephrotoxicity, infusion reactions and hypomagnesemia than ABLC in patients at increased risk of nephrotoxicity.

Incremental Healthcare Costs and Outpatient Antifungal Treatment of Patients with Aspergillosis in the United States.

Objectives: To evaluate the total and outpatient economic burden of aspergillosis, and to describe the outpatient antifungal treatment of aspergillosis within a large, commercially-insured population in the United States. Methods: Adults with at least one medical claim with an aspergillosis diagnosis (International Classification of Disease 9th Revision Clinical Modification [ICD-9-CM] code 117.3 or 484.6) between 07/01/04-03/01/11 were identified from the MarketScan Research Databases. Patients had ≥6 months of pre-index and ≥1 month of post-index continuous health plan and pharmacy benefit enrollment and no pre-index diagnosis of aspergillosis. Aspergillosis cases were propensity score-matched to a sample of controls without aspergillosis. Outpatient antifungal therapy and total and outpatient healthcare resource utilization were evaluated in the post-index period. General linear models were used to estimate costs, which were adjusted by the length of follow-up. Incremental costs were calculated between cohorts and a bootstrap procedure was used to produce corresponding variation and 95% confidence interval estimates. Results: Aspergillosis cases (N=5,499; mean age: 57.8 years; 48.6% female; 64.2% with cancer) were matched to 5,499 controls (mean age: 58.3 years; 48.4% female; 60.6% with cancer). Two-thirds of the aspergillosis cases had no outpatient prescription for an antifungal within 30 days of index; for those with outpatient antifungal therapy, voriconazole was the most commonly prescribed agent (60.9%). Average adjusted total and outpatient expenditures were greater for aspergillosis patients during follow-up than those of the matched controls ($26,680 and $9,248 greater, respectively). Conclusions: The economic burden of aspergillosis is substantial. Patients with aspergillosis utilize significantly more healthcare resources and thus incur greater healthcare costs than do similar patients without aspergillosis.

Development and validation of a bedside risk score for MRSA among patients hospitalized with complicated skin and skin structure infections.

BACKGROUND: Methicillin-resistant Staphylococcus aureus (MRSA) is a frequent cause of complicated skin and skin structure infections (cSSSI). Patients with MRSA require different empiric treatment than those with non-MRSA infections, yet no accurate tools exist to aid in stratifying the risk for a MRSA cSSSI. We sought to develop a simple bedside decision rule to tailor empiric coverage more accurately. METHODS: We conducted a large multicenter (N=62 hospitals) retrospective cohort study in a US-based database between April 2005 and March 2009. All adult initial admissions with ICD-9-CM codes specific to cSSSI were included. Patients admitted with MRSA vs. non-MRSA were compared with regard to baseline demographic, clinical and hospital characteristics. We developed and validated a model to predict the risk of MRSA, and compared its performance via sensitivity, specificity and other classification statistics to the healthcare-associated (HCA) infection risk factors. RESULTS: Of the 7,183 patients with cSSSI, 2,387 (33.2%) had MRSA. Factors discriminating MRSA from non-MRSA were age, African-American race, no evidence of diabetes mellitus, cancer or renal dysfunction, and prior history of cardiac dysrhythmia. The score ranging from 0 to 8 points exhibited a consistent dose-response relationship. A MRSA score of 5 or higher was superior to the HCA classification in all characteristics, while that of 4 or higher was superior on all metrics except specificity. CONCLUSIONS: MRSA is present in 1/3 of all hospitalized cSSSI. A simple bedside risk score can help discriminate the risk for MRSA vs. other pathogens with improved accuracy compared to the HCA definition.

Treatment of candidemia with echinocandins: data on hospital resource use from a real world setting.

OBJECTIVE: Real-world data on patients treated with echinocandins for candidemia are limited. This study examined the effect of three echinocandin-based treatment regimens on resource utilization in patients with Candida infection. RESEARCH DESIGN AND METHODS: A retrospective cohort study of patients hospitalized between 2005 and 2010 with a blood culture positive for Candida. Length of stay (LOS) following AF initiation (post-AF LOS) and total days with AF treatment were compared in patients treated with three different echinocandin regimens: patients with echinocandin only, patients who received fluconazole prior to an echinocandin (fluconazole-echinocandin), and patients who received an echinocandin prior to fluconazole (echinocandin-fluconazole). Generalized linear models were used to adjust for confounders. RESULTS: A total of 647 patients met inclusion criteria. Patients treated with echinocandin only were more acutely ill, having more organ dysfunction and sepsis. Unadjusted post-AF LOS was significantly greater in the groups that received both echinocandin and fluconazole (mean, 13.1 days for echinocandin-only vs 25.5 and 21.2 days for fluconazole-echinocandin and echinocandin-fluconazole groups, respectively, p<0.001). These groups also had a higher total number of days with AF orders. These differences remained after multivariate adjustment and in survivor-only analyses. Compared with echinocandin-only treatment, the average marginal effect of fluconazole-echinocandin and echinocandin-fluconazole regimens were associated with significantly longer adjusted post-AF LOS (by 7.2 days and 9.3 days, respectively, p<0.001) and significantly more adjusted total AF days (by 5.3 days for fluconazole-echinocandin and 6.5 days for echinocandin-fluconazole patients, p<0.001). Limitations included lack of visibility to specific reasons for therapy changes. CONCLUSIONS: Fluconazole before or after echinocandin was associated with significantly greater resource utilization than echinocandin use alone.

Quality of care for 2 common pediatric conditions treated by convenient care providers.

Rates of adherence to 2 quality measures, modeled after Heathcare Effectiveness Data and Information Set (HEDIS) measures, were evaluated in a pediatric population in a convenient care (retail medicine) clinic setting. The measures were appropriate testing for children with pharyngitis and appropriate treatment for children with upper-respiratory infection (URI). The convenient care clinic (CCC) achieved a ranking above the HEDIS 90th percentile for the pharyngitis measure and approximately midway between the 50th and 90th percentiles for the URI measure for the 2007 reporting period. This represents the third major study reporting quality of care for pharyngitis in a CCC setting and the first study for URIs. Other aspects of quality--namely access, follow-up, and equity--are also reported on for the population in question.

The impact of rheumatoid arthritis and biologics on employers and payers.

Paresh Chaudhari, PharmD, MPH, frames the business case for employers to look beyond the direct medical costs of treatment of RA and consider employee health benefits as an investment.

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.