The impact of initial statin treatment decisions on cardiovascular outcomes in clinical care settings: estimates using the Archimedes Model.

PURPOSE: Many patients treated for dyslipidemia do not achieve recommended cholesterol goals despite the widespread availability of effective statins. Pharmaceutical claims show a strong tendency for patients to remain on their initially assigned treatment. With computer simulations, the impact of initial statin treatment decisions on medium- and long-term cardiovascular outcomes were examined. PATIENTS AND METHODS: Using the Archimedes Model, three treatment scenarios were simulated. Patients initiated treatment with simvastatin (20, 40, or 80 mg), atorvastatin (10, 20, 40, or 80 mg), or rosuvastatin (10, 20, or 40 mg), and periodically intensified treatment. The simulated population consisted of 50,025 patients, aged 45-70 years, with low-density lipoprotein cholesterol exceeding goal. The proportion of patients initiating each dose was calibrated to United States pharmacy claims. Patients not reaching goal intensified the dose of their current statin or switched to an appropriate dose of rosuvastatin at rates matching pharmacy claims. Biomarkers and major adverse cardiovascular events (MACE) were tracked for 10 years and several high-risk subpopulations were analyzed. Statin models used biomarker effects from the STELLAR (Statin Therapies for Elevated Lipid Levels Compared Across Doses to Rosuvastatin) trial and outcomes data from various trials. RESULTS: Initiating therapy with rosuvastatin reduced MACE more than simvastatin or atorvastatin. The 5- year relative risk of MACE was 0.906 (95% confidence interval: 0.888-0.923; P < 0.001) for initial treatment with atorvastatin rather than simvastatin, 0.831 (0.812-0.850; P < 0.001) for rosuvastatin rather than simvastatin, and 0.918 (0.898-0.938; P < 0.001) for rosuvastatin rather than atorvastatin. Subgroups with higher MACE incidence experienced greater absolute benefit. CONCLUSION: Considering observed rates of treatment intensification, initial treatment choices appear to significantly impact medium- and long-term cardiovascular risk. Patients at high cardiovascular risk are good candidates for aggressive initial therapy.

Adherence to single-pill combination versus multiple-pill combination lipid-modifying therapy among patients with mixed dyslipidemia in a managed care population.

BACKGROUND: Suboptimal adherence to lipid-lowering therapies is associated with and potentially contributes to increased cardiovascular morbidity and mortality. Single-pill combination (SPC) lipid-modifying therapies may improve patient adherence due to decreased pill burden and increased convenience for the patient. OBJECTIVE: To compare adherence to SPC versus multi-pill combination (MPC) lipid-modifying medications. METHODS: This retrospective study used pharmacy and medical claims and laboratory result data from a national managed care dataset to evaluate patients who were newly prescribed simvastatin plus ezetimibe, simvastatin plus niacin, and lovastatin plus niacin either as SPC or MPC. Patients were considered adherent to therapy if they had a proportion of days covered (PDC) ≥ 0.80. RESULTS: The mean PDC was 0.76 and 0.70 in the first 3 months of therapy, 0.54 and 0.45 in the second 3 months, and 0.50 and 0.41 for the remaining 30 months of follow-up for the SPC and MPC groups, respectively. SPC patients were 32% (OR = 1.32; 95% CI: 1.27-1.36; P < 0.01) more likely to be adherent to treatment than MPC patients. CONCLUSION: Adherence was significantly higher among patients receiving SPC than MPC. Although only associations and not temporality were assessed due to the observational design of this study, the use of SPC may be a successful method for improving adherence in a real-world setting.

Medical and cost burden of atherosclerosis among patients treated in routine clinical practice.

OBJECTIVE: This investigation estimated medical costs attributable to treatment of patients diagnosed with atherosclerosis in routine US clinical practice. METHODS: Using Medstat MarketScan claims data, direct costs of care and rates of cardiovascular (CV) events (i.e., myocardial infarction, stroke, revascularization) were examined for patients≥18 years of age with and without a diagnostic code for atherosclerosis from 1/1/2002 through 12/31/2004. Patients with an atherosclerosis ICD-9 code who had no history of CV events in the preceding 12 months (n=75,469) were evaluated. A comparison cohort (n=238,702) was matched on age, gender, geographic region, enrollment time period, and Charlson comorbidity index to estimate incremental costs attributable to atherosclerosis. Differences between patient groups were tested for CV event rates per 1,000 patients and monthly costs for 6 and 12 months before and after diagnosis. RESULTS: Patients had a mean age of 58 years, 52% men, and a comorbidity index of 0.49. Patients diagnosed with atherosclerosis had significantly higher (p<0.001) rates of CV events (240/1000) after diagnosis, compared with patients without atherosclerosis (32/1000). Mean direct cost of care for patients diagnosed with atherosclerosis was $579/month for 12 months before and $1,074/month for 12 months after diagnosis, an 85% increase. Change in mean annual costs pre/post-index date was $5,232 ($436/month) higher among patients with than those without atherosclerosis (p<0.001). LIMITATIONS: The study population was restricted to patients with diagnosed clinical atherosclerosis based on specific ICD-9 codes. Matching of the patient cohorts was based on observed characteristics and other unobserved differences may exist. CONCLUSIONS: Patients with diagnosed atherosclerosis incur significant clinical and economic burden, indicating a need for earlier diagnosis and treatment of atherosclerosis to help in reducing this burden.

Managing dyslipidemia in primary care with restricted access to lipid-modifying therapy.

BACKGROUND: Many patients with dyslipidemia do not achieve goal low-density lipoprotein cholesterol levels. The barriers to achieving goal include inadequate assessment of cardiovascular risk status, medication cost, formulary restrictions, patient lack of adherence, and inadequate counseling time. Removing barriers may improve goal attainment and reduce the risk for cardiovascular events. OBJECTIVE: To identify opportunities to improve dyslipidemia management in primary care by examining low-density lipoprotein cholesterol goal attainment in patients with unrestricted or restricted access to lipid-modifying therapy. METHOD: A total of 5936 adult patients from a primary care practice with a low-density lipoprotein measurement were categorized by coronary heart disease risk into 1 of 4 lipid-modifying therapy groups: unrestricted (fluvastatin, lovastatin, pravastatin, or simvastatin monotherapy); restricted (atorvastatin, rosuvastatin, or simvastatin/ezetimibe fixed-dose combination); other (lipid-modifying combination statin therapy or a nonstatin lipid-modifying therapy); and no lipid-modifying therapy. The primary outcome was low-density lipoprotein cholesterol goal attainment by lipid-modifying therapy group. Logistic regression identified associated demographic and clinical factors. RESULTS: In this cohort, 78.1% of the patients achieved low-density lipoprotein cholesterol goal levels. Overall goal attainment rates were lower in the high and very high coronary heart disease risk categories, at 52.6% and 31.6%, respectively. For patients at elevated coronary heart disease risk (high or very high), the rates of low-density lipoprotein cholesterol goal attainment were 14 to 16 percentage points higher for patients receiving restricted lipid-modifying therapy compared with patients receiving unrestricted lipid-modifying therapy (high coronary heart disease risk: 68% vs 52%, respectively; very high coronary heart disease risk: 42% vs 28%, respectively). Increasing age, male sex, and use of restricted lipid-modifying therapy were significantly associated with improved low-density lipoprotein cholesterol goal attainment. Of the 1298 patients who were not at low-density lipoprotein cholesterol goal, 54.1% were not receiving any lipid-modifying therapy. For each coronary heart disease risk category, there was a significantly higher percent utilization of unrestricted lipid-modifying therapy compared with restricted lipid-modifying therapy (P <.001). CONCLUSION: A significant number of patients at elevated risk for coronary heart disease remain untreated or have low-density lipoprotein cholesterol levels above target. Removing barriers to the use of restricted lipid-modifying agents in patients at risk for heart disease provides an opportunity to improve low-density lipoprotein cholesterol levels.

Therapy modifications and low-density lipoprotein cholesterol goal attainment rates associated with the initiation of generic simvastatin.

OBJECTIVE: The availability of generic simvastatin has changed the relative cost structure within the statin marketplace and has been associated with third-party payer changes to formularies and statin utilization policies. The current study examines simvastatin therapy modification patterns and associated low-density lipoprotein cholesterol (LDL-C) goal attainment rates. METHODS: This retrospective, observational study utilized administrative claims linked to laboratory result data from a national health plan. Patients newly initiated on generic simvastatin from January 2007 to March 2008 were identified. National Cholesterol Education Program Adult Treatment Panel III (NCEP ATP III) risk categories and goal LDL-C targets were assigned. Simvastatin dose titrations and switches to other statins were described, as were changes in LDL-C values and NCEP ATP III goal attainment rates both before and after therapy modifications. RESULTS: Of the 1654 patients newly initiated on simvastatin, 84% had no simvastatin therapy modification in the >1-year follow-up period. For patients with no therapy modification, 54.4% did not achieve their LDL-C NCEP ATP III goal at their first lipid panel and goal attainment was strongly associated with the level of cardiovascular risk (goal attainment rate = 75.1%, 51.7%, and 28.6% for low-, moderate- and high-risk categories, respectively). Of patients not achieving NCEP ATP III LDL-C goals (n = 885), 85.4% had no therapy modification. Goal was achieved after therapy modification in 36% (dose titration) and 42% (switchers); high-risk patients goal attainment rates were 23% and 38%, respectively. LIMITATIONS: LIMITATIONS of the study include the observational design, use of an administrative claims database to assess cardiovascular risk, relatively short follow-up time (slightly more than 1 year) and the lack of assessment of adherence to therapy. CONCLUSIONS: This study found that the majority of patients initiated on generic simvastatin stayed on their initial starting dose regardless of NCEP ATP III goal attainment status. The findings of low rates of therapy modification irrespective of baseline CV risk and associated low rates of goal attainment, especially in high risk patients treated with simvastatin, indicate an opportunity to encourage clinical decision making based on the needs of the individual patient.

Knowledge of heart disease risk among SHIELD respondents with dyslipidemia.

BACKGROUND: Respondents in the US Study to Help Improve Early evaluation and management of risk factors Leading to Diabetes (SHIELD) reported whether they had a diagnosis of dyslipidemia, were taking prescription dyslipidemia medication, and knew their heart disease risk (low, moderate, high, or do not know). We assessed whether respondents who reported a diagnosis of dyslipidemia with or without lipid-modifying treatment knew their heart disease risk and whether it correlated with National Cholesterol Education Program Adult Treatment Panel (ATP) III risk. METHODS AND RESULTS: Based on self-report of risk factors, ATP III high risk was defined as diagnosis of heart disease/heart attack, narrow/blocked arteries, stroke, or diabetes; moderate risk included >or=2 risk factors (ie, men aged >45 years, women aged >55 years, hypertension, low high-density lipoprotein cholesterol, current smoking, and family history of CHD); and low risk included <2 risk factors. Of 7629 respondents with dyslipidemia, 35% reported not taking cholesterol medication, and 29% reported not knowing their heart disease risk. For respondents treated for dyslipidemia, 27% reported not knowing their risk, and of the 73% who reported knowing, 24% to 35% reported the same risk level as ATP III risk. For respondents with untreated dyslipidemia, 33% reported not knowing their risk, and of the 67% who reported knowing, 20% to 37% reported the same risk as ATP III risk. CONCLUSIONS: A large proportion of respondents with dyslipidemia did not know their heart disease risk. Among those who reported knowing their risk level, >60% of respondents did not classify themselves at the same ATP III-defined risk level. There is a gap in understanding and awareness of heart disease risk among respondents with dyslipidemia regardless of treatment status.

Atherosclerosis profile and incidence of cardiovascular events: a population-based survey.

BACKGROUND: Atherosclerosis is a chronic progressive disease often presenting as clinical cardiovascular disease (CVD) events. This study evaluated the characteristics of individuals with a diagnosis of atherosclerosis and estimated the incidence of CVD events to assist in the early identification of high-risk individuals. METHODS: Respondents to the US SHIELD baseline survey were followed for 2 years to observe incident self-reported CVD. Respondents had subclinical atherosclerosis if they reported a diagnosis of narrow or blocked arteries/carotid artery disease without a past clinical CVD event (heart attack, stroke or revascularization). Characteristics of those with atherosclerosis and incident CVD were compared with those who did not report atherosclerosis at baseline but had CVD in the following 2 years using chi-square tests. Logistic regression model identified characteristics associated with atherosclerosis and incident events. RESULTS: Of 17,640 respondents, 488 (2.8%) reported having subclinical atherosclerosis at baseline. Subclinical atherosclerosis was associated with age, male gender, dyslipidemia, circulation problems, hypertension, past smoker, and a cholesterol test in past year (OR = 2.2) [all p < 0.05]. Incident CVD was twice as high in respondents with subclinical atherosclerosis (25.8%) as in those without atherosclerosis or clinical CVD (12.2%). In individuals with subclinical atherosclerosis, men (RR = 1.77, p = 0.050) and individuals with circulation problems (RR = 2.36, p = 0.003) were at greatest risk of experiencing CVD events in the next 2 years. CONCLUSION: Self-report of subclinical atherosclerosis identified an extremely high-risk group with a >25% risk of a CVD event in the next 2 years. These characteristics may be useful for identifying individuals for more aggressive diagnostic and therapeutic efforts.

LDL-C goal attainment among patients newly diagnosed with coronary heart disease or diabetes in a commercial HMO.

BACKGROUND: Patients beginning treatment with lipid-modifying drugs should have their serum lipid levels monitored and, if necessary, their drug therapy adjusted to reach and maintain their treatment goals. Patients with coronary heart disease or diabetes are at high risk of coronary events and are particularly important target groups for monitoring and dose adjustment of lipid-modifying drug therapy. OBJECTIVE: to determine from administrative claims the rates of lipid testing, treatment with low-density lipoprotein cholesterol (LDL-C)-lowering drug therapy, and LDL-C goal attainment defined as LDL-C < 100 mg per DL in the time period after a new diagnosis of coronary heart disease or diabetes among patients who had not previously received lipid-modifying drug therapy. METHODS: an index date was defined by a new diagnosis of coronary heart disease or diabetes between January 1, 1999 and December 31, 2000, preceded by a 12-month pre-index period without lipid-modifying drug treatment in a commercial health maintenance organization (HMO) database for the southeastern united states. coronary heart disease (CHD) was defined by a diagnosis code for myocardial infarction (International Classification of Diseases, Ninth Edition, Clinical Modification [ICD-9-CM] code 410.xx) or angina/ischemic heart disease (411.xx), or a procedural code for angioplasty (icd-9-cM 36.1x-36.3x; Current Procedural Terminology [CPT] 92980-92984, 92995-92996) or coronary artery bypass graft (icd-9-cM 36.01, 36.02, 36.05, 36.09; CPT 33510-33545). diabetes was identified either by an icd-9-cM diagnosis code 250.xx or a pharmacy claim for an antihyperglycemic medication. Patients were followed in the post-index period until loss of eligibility or a maximum of 42 months (mean = 26 months, range=12-42 months). We calculated the proportion of patients with lipids treated and at LDL-C goal (defined as V < 100 mg per DL) in months 1-6 after the index date. among those not at goal in months 1-6, we estimated the proportion treated to goal in months 7-12 and in month 7 to the end of the post-index period. Logistic regression was used to estimate the odds of goal attainment in months 7-12 and in month 7 to the end of the post-index period among patients who were not at goal in months 1-6. RESULTS: Laboratory lipid values were available for 4,676 (40.4%) of 11,552 patients who had not previously received lipid-modifying drug therapy in months 1-6 after the index date, of whom 72.7% (n = 3,400) had an LDL-C > or =100 mg per DL (63.5% for CHD and 76.7% for diabetes). Of 1,245 patients tested and treated with lipid-modifying therapy in months 1-6, 485 (39.0%) were at LDL-C goal in months 1-6 (48.2% of CHD and 28.8% of diabetes patients), and 760 (61.0%) were not at LDL-C goal (51.8% of those with CHD and 71.2% of those with diabetes). Goal attainment (cumulative) among those treated improved to 50.1% in months 7-12 and 58.4% in month 7 to the end of the post-index period. Patients not attaining goal in months 1-6, and who continued treatment in months 7-12 and month 13 to the end of the post-index period, had a 48.8% (95% confidence interval [CI], 44.0%-53.6%) predicted probability of attaining their goals. The odds of goal attainment in month 7 to the end of post-index period (among those not at goal in months 1-6) were greater for (a) age e 65 years (odds ratio [or] = 2.45, 95% CI, 1.62-3.72), (b) history of hypertension (or = 1.91, 95% CI, 1.20-3.03), (c) greater number of distinct medications (or = 1.07, 95% CI, 1.01-1.14 per additional medication), (d) months of observation post-index (or = 1.04, 95% CI = 1.01-1.08 per additional month), and (e) months supply of lipid-modifying medication (or = 1.04, 95% CI, 1.01-1.07 per additional month), and were lower for LDL-C > or = 130 mg per DL in months 1-6 (or = 0.53, 95% CI, 0.35-0.82) and a history of dyslipidemia (or = 0.54, 95% CI, 0.35-0.83). The odds of LDL-C goal attainment were not affected by diagnosis (CHD vs. diabetes), gender, statin titration (34% of patients), lipid-modifying drug switching (39% of patients), or treatment with a high-potency LDL-C-lowering drug dosage (one of sufficient strength to reduce LDL-C by > 40%). CONCLUSION: of patients receiving lipid testing and lipid drug treatment in the 6 months after an initial diagnosis of CHD or diabetes, 61% were not at the LDL-C goal of < 100 mg per DL. Among those not at LDL-C goal in the first 6 months of treatment, only about half who continued treatment subsequently attained their LDL-C goal, despite statin titration or switching of their lipid-modifying drug therapy.

Effectiveness of rosuvastatin versus atorvastatin in reducing lipid levels and achieving low-density-lipoprotein cholesterol goals in a usual care setting.

PURPOSE: The effectiveness of rosuvastatin versus atorvastatin in reducing lipid levels and achieving low-density-lipoprotein (LDL) cholesterol goals in patients treated in a usual care setting was studied. METHODS: Electronic medical and pharmacy administrative claims from a western U.S. health plan with approximately 8 million covered members were extracted and used in this retrospective, longitudinal cohort study. Patients age 18 years or older who were newly initiated on rosuvastatin or atorvastatin between August 1, 2003, and June 30, 2004, were included. Propensity-score matching on baseline characteristics was used to minimize selection bias between groups. Administrative claims and medical records were used to assign patients a cardiovascular risk status and corresponding LDL cholesterol goal using guidelines from the National Cholesterol Education Program (NCEP). Changes in lipid levels and attainment rates of goal LDL cholesterol levels were estimated after accounting for baseline covariates using regression techniques. RESULTS: A total of 453 patients met the study criteria. The mean dose of rosuvastatin was 11 mg compared with 15 mg for atorvastatin. After adjusting for baseline differences between groups, patients receiving rosuvastatin had significantly greater mean percent reductions in LDL cholesterol, total cholesterol, and non-high-density-lipoprotein (non-HDL) cholesterol than did patients receiving atorvastatin (p < 0.001 for all comparisons). No significant differences were found in HDL cholesterol and triglyceride levels between groups. Attainment rates for NCEP LDL cholesterol goals were significantly higher in patients receiving rosuvastatin. CONCLUSION: Patients treated in a usual care setting with rosuvastatin had significantly greater reductions in LDL cholesterol, non-HDL cholesterol, and total cholesterol levels compared with those receiving atorvastatin. Patients receiving rosuvastatin were more likely to attain NCEP LDL cholesterol goals compared with patients treated with atorvastatin.

Understanding practice patterns and low-density lipoprotein cholesterol goal attainment implications of switching patients from simvastatin in a health plan setting.

OBJECTIVE: To understand the practice patterns and National Cholesterol Education Panel (NCEP) Adult Treatment Panel (ATP) III low-density lipoprotein cholesterol (LDL-C) goal attainment rates after switching patients from simvastatin (SMV) to other statins or the combination of SMV and ezetimibe (EZE). METHODS: This retrospective study linked claims and laboratory data from a national health plan. Patients were included if they were taking SMV and were switched to other statins or a fixed-dose combination of SMV and EZE between July 1, 2005, and June 30, 2006. Patients taking dual SMV/EZE before switch were excluded from the study. The NCEP ATP III risk status of patients at switch was assessed based on medical claims, pharmacy claims, and laboratory values in the 12-month preswitch period. Lipid data (available on a patient subset) were used to estimate patients' goal attainment status at and after switch. RESULTS: Of 134 168 patients taking SMV, 11 929 (8.9%) switched to other statins or SMV/EZE. The mean age of switching patients was 54 years (standard deviation, 9 years), 61% were men, 50% were high risk, and 30% were moderate risk. The mean time to switch among new starters of SMV (n = 3379) was 77 days. Forty percent (n = 4772) of the total switches occurred among those taking the lower doses (5, 10, and 20 mg) of SMV. Most patients switched from SMV to SMV/EZE (60.5%), followed by atorvastatin (17.3%), rosuvastatin (10.1%), lovastatin (8.6%), pravastatin (2.9%), and fluvastatin (0.7%). Similarly, most patients switching from higher doses of SMV switched to SMV/EZE (52.5%), followed by atorrestatin (21.1%) and rosuvastatin (10.1%). Overall, 55.6% (758 of 1362) of patients were at ATP III goal at the time of switch from SMV (across all doses; n = 758), and 56.1% (292 of 521) of those taking lower doses were at goal at time of switch. A majority (69.9%) of patients who were at goal and switched from SMV (across all doses) were switched to SMV/EZE, and 61.6% of those at lower doses of SMV switched to the combination drug. Of patients who were not at goal at switch (n = 604), 73.3% attained ATP III LDL-C goal after switch. The mean percent LDL-C reduction that was needed to attain LDL-C goal at switch from SMV (n = 604) was 18.1%. CONCLUSIONS: There is an opportunity to further increase LDL-C goal attainment rates among patients switched from SMV. The clinical, prescription benefit design, and economic implications of the finding that a majority of patients are at goal when switched from SMV and a majority of patients are being switched from SMV to SMV/EZE need to be further examined.

Hypoglycemic events and glycosylated hemoglobin values in patients with type 2 diabetes mellitus newly initiated on insulin glargine or premixed insulin combination products.

PURPOSE: Rates of hypoglycemic events and their associated costs were compared among patients with type 2 diabetes mellitus newly initiated on insulin glargine or a premixed insulin fixed-combination product. METHODS: Patients newly initiated on insulin glargine or premixed insulin fixed-combination products (including pen delivery systems) between June 1, 2001, and February 29, 2004, were identified using an administrative claims database. Hypoglycemic events were identified from International Classification of Diseases, 9th Revision, Clinical Modification codes. Multivariate analyses were performed. RESULTS: A total of 2315 patients met the inclusion criteria. Of those, 1212 received insulin glargine and 1103 received a premixed fixed-combination insulin product. The mean +/- S.D. treatment duration was 13.7 +/- 8.1 months. Patients treated with premixed insulin had a higher hypoglycemic event rate than glargine patients (13.8 versus 7.0/100 patients/year; p = 0.027), which yielded a number needed to treat of 15 patients. The mean cost per hypoglycemic event was $1049 (95% confidence interval, $426-1672). The mean annual cost of all insulin use was $46 more for the insulin glargine cohort than for those who received premixed insulin ($534 versus $488, respectively) (p < 0.05). Mean postindex insulin use was higher in patients receiving premixed insulin than in those treated with insulin glargine (48.1 versus 43.8 units per day) (p < 0.05). CONCLUSION: Patients with type 2 diabetes mellitus who were newly initiated on insulin glargine had a lower rate of hypoglycemic events compared with patients newly initiated on a premixed fixed-combination insulin product. Treatment of 15 patients with insulin glargine instead of premixed insulin for one year would avoid one hypoglycemic event per year.

Comparison of costs associated with the use of etanercept, infliximab, and adalimumab for the treatment of rheumatoid arthritis.

A retrospective study of health plan costs related to rheumatoid arthritis (RA) revealed that etanercept was associated with the lowest drug and outpatient costs to the health plan than infliximab and adalimumab. Compared with etanercept, infliximab was related to 55% higher postindex RA-related monthly total health care costs paid by the health plan, based on adjusted analyses (95% confidence interval, 1.47-1.64). Patients receiving adalimumab had 12% higher costs (95% confidence interval, 1.04-1.21). The study showed the average dispensing dose increase was greatest for infliximab (17.4%) and least for etanercept (4.1%).

Monitoring anticoagulation in atrial fibrillation.

BACKGROUND: Randomized control trials and observational studies show high-quality warfarin therapy leads to safe and effective stroke prophylaxis. In usual community practice, patient, physician and health care system factors are barriers to optimal anticoagulation. We examined the predictive relationship between inpatient and outpatient INR values in chronic non-valvular atrial fibrillation (AF) patients hospitalized for ischemic stroke (S), bleed (B) and control events (C) in usual community practice. METHODS: This nested case-control analysis identified AF patients hospitalized for S, B and C using medical and pharmacy claims spanning 4.5 years ('98-'03) and validating diagnosis with chart abstraction. AF was defined as 2 medical claims for AF >or= 42 days apart with a related prescription claim for warfarin. INRs from both outpatient and inpatient settings were used to yield a continuous history of coagulation status. Time-in-therapeutic-range (TTR) was calculated by Rosendaal's linear interpolation method. Correlation of inpatient and prognostic utility of last outpatient INRs was tested with S or B hospitalizations using univariate and multivariate logistic regression. RESULTS: Overall, 614 hospitalizations (means: age 73.9, CHADS(2) = 3.24; 52% male) included S (n = 98), B (n = 101) and C (n = 415) events. Average TTR was 28.6% (49.4% at INR <2.0, 21.9% at INR >3.0). First INR on admission (INR <2.0 or >3.0) was associated with S and B hospitalizations (OR-adjusted [95%CI], 1.68 [1.04-2.73] and 1.72 [1.02-2.90]), respectively. Last outpatient INR <2.0 was not associated with S (OR-adjusted [95%CI], 1.12 [0.77-1.81]), and INR >3.0 was not associated with B (OR-adjusted [95%CI], 1.25 [0.67-2.32]). Last outpatient INR measurement occurred at 28, 22 and 24 days (median; S, B & C, respectively) before hospitalization. CONCLUSION: Patients were observed within therapeutic range less than 30% of their time on warfarin. While inpatient INRs were clearly associated with both ischemic stroke and bleed events, last outpatient INR before event was not predictive.

Agreement between administrative claims and the medical record in identifying patients with a diagnosis of hypertension.

OBJECTIVE: This study evaluated the accuracy of 2 administrative claims-based selection rules to identify patients with hypertension (HTN) using medical records as the gold standard. RESEARCH DESIGN: The claims database consisted of inpatient, outpatient, pharmacy, and eligibility claims for members of a single insurance company from January 2000 through March 2003. Medical records were abstracted for 258 matched patient pairs selected by Rule A (at least 1 HTN-related International Classification of Diseases, 9th Revision [ICD-9] claim) and 138 pairs selected by Rule B (at least 1 HTN-related ICD-9 and at least 1 HTN prescription claim) from 31 provider sites. Sensitivity and specificity of the 2 selection rules were computed using medical chart review as the gold standard for a diagnosis of HTN. SUBJECTS: Of patients selected by Rule A, chart review identified 281 patients with and 235 patients without HTN. Of patients selected by Rule B, chart review identified 172 patients with and 104 patients without HTN. RESULTS: The sensitivity and specificity was 70.8% and 74.9% for Rule A and 76.2% and 93.3% for Rule B. The kappa score was 0.45 for Rule A and 0.65 for Rule B. CONCLUSION: To identify patients with HTN, a selection rule using both a diagnosis and prescription claim has greater sensitivity and specificity than a rule using a diagnosis claim only.

Effect of rosuvastatin compared with other statins on lipid levels and National Cholesterol Education Program goal attainment for low-density lipoprotein cholesterol in a usual care setting.

STUDY OBJECTIVE: To compare, in a usual care setting, the effects of rosuvastatin and other 3-hydroxy-3-methylglutaryl coenzyme A inhibitors (statins) on lipid levels and on goal attainment of low-density lipoprotein cholesterol (LDL) levels from the National Cholesterol Education Program (NCEP) third report of the Adult Treatment Panel (ATP III). DESIGN: Retrospective, longitudinal, cohort study. DATA SOURCE: Managed care medical and pharmacy claims and laboratory database. PATIENTS: A total of 8251 patients starting treatment with rosuvastatin, atorvastatin, simvastatin, pravastatin, lovastatin, or fluvastatin from August 1, 2003-September 30, 2004, excluding those who received dyslipidemic therapy in the previous 12 months. MEASUREMENTS AND MAIN RESULTS: Patients with at least one pretreatment and posttreatment lipid level were followed until their initial statin was changed or they reached the end of benefit eligibility or the study period. Percent changes in lipid levels were calculated, and adjusted changes in LDL and goal attainment were evaluated by regression techniques. Absolute and percent reductions in LDL, triglyceride, and total cholesterol levels were significantly greater with rosuvastatin than with other statins (all p<0.05 except for triglyceride reduction vs atorvastatin). After adjustment for age, sex, and baseline LDL, percent LDL reductions still were significantly greater with rosuvastatin than with other statins (p<0.05). Changes in high-density lipoprotein cholesterol were not significant. Goal attainment was higher with rosuvastatin than with other statins after adjustment for age, sex, baseline LDL, risk status, dose, and duration of therapy (p<0.05). Dose-stratified analysis showed that LDL goal attainment was significantly higher with rosuvastatin 10 mg than with atorvastatin 10 or 20 mg. CONCLUSION: Rosuvastatin was more effective than other statins in reducing LDL, triglyceride (except vs atorvastatin), and total cholesterol levels. Significantly more patients taking rosuvastatin than patients taking other statins attained their LDL goals.

Longitudinal evaluation of health plan cost per venous thromboembolism or bleed event in patients with a prior venous thromboembolism event during hospitalization.

OBJECTIVE: To measure the per-event health plan costs for acute and follow-up treatment not directed by a clinical study protocol in a group of commercially insured patients in 2 managed care organizations following an incident hospitalization that included a diagnosis for a venous thromboembolism (VTE) event. METHODS: A cohort of patients with an incident in-hospital VTE event, consisting of deep vein thrombosis (DVT), or pulmonary embolism (PE), or both DVT + PE, was retrospectively identified from the administrative claims databases of 2 large U.S. health care plans. Inclusion criteria were (a) an inpatient VTE event between January 1, 1998, and December 31, 2000, (b) no VTE diagnosis or anticoagulation therapy 3 months prior to the incident VTE in-hospital event, (c) at least 1 anticoagulation pharmacy fill following the incident hospital VTE, and (d) continuous health plan enrollment 3 months prior to and 6 months following the incident hospital VTE event. Total costs were reported on a per-event basis and consisted of the aggregated amount paid by the health plan to the provider after subtraction of member cost-share. Costs were collected separately, first for the incident VTE event for all patients identified and second for patients who had at least 1 of the following events in the follow-up period: bleed requiring or not requiring hospitalization, a recurrent VTE event requiring hospitalization, or a recurrent VTE and bleed (VTE + bleed) event requiring hospitalization. Costs were compared between incident diagnosis groups using multivariate generalized linear model techniques. RESULTS: A total of 2,147 patients (DVT=1,499 [69.8%], PE=373 [17.4%], DVT+PE= 275 [12.8%]) were identified (mean age=61.6standard deviation [SD] 16 years; 46.3% male) and were followed for an average of 21.3 (median, 19.2) months. Disease severity was high in these patients, including 59.2% with a history of or active malignancy. The prevalence of VTE was 2.04 per 100,000 study-eligible health plan members. For the incident VTE events, average costs were 7,712+/-18,339 US dollars (median, 3,131 US dollars) per incident DVT event; 9,566+/-13,512 US dollars (median, 6,424 US dollars) per PE incident event; and 12,200+/-24,038 US dollars (median, 6,678 US dollars) per incident DVT+PE event. Warfarin treatment following the incident VTE event was administered to 97.3% of patients for an average of 6.7 (median, 5.0) months at an average cost of 19.40 US dollars per patient per month. During the average period of 21.3 months, 534 patients (24.9%) experienced an average of 1.24 bleed or recurrent VTE events per patient that required hospitalization at a mean cost of 14,975 US dollars per event or 2,101 US dollars per patient per year. For patients with a bleed in the follow-up period that required hospitalization, average costs were 12,326+/-24,448 US dollars (median, 5,736 US dollars) per recurrent VTE; 15,339+/-52,029 US dollars (median, 4,999 US dollars) per bleed; or 24,085+/-65,411 US dollars (median, 10,185 US dollars) per recurrent VTE + bleed event. During the follow-up period, a total of 612 patients (28.5%) experienced 1,489 recurrent bleed events that did not require hospitalization, at an average cost of 239+/-386 US dollars (median, 95 US dollars) per event. There were no significant differences in mean total costs for all pair-wise comparisons between the 3 incident diagnosis groups. CONCLUSIONS: Of patients who experienced a VTE event during the incident hospital stay for any diagnosis, 1 in 4 experienced an average of 1.24 bleed or recurrent VTE events that required hospitalization in the 21 months of follow-up and incurred an average health plan cost of 14,957 US dollars per event. These data may be of interest to managed care decision makers when evaluating the cost impact of new therapies or providing more comprehensive anticoagulation management services for existing therapies.

Association between short-term effectiveness of statins and long-term adherence to lipid-lowering therapy.

PURPOSE: The relationship between low-density lipoprotein (LDL) cholesterol reduction in the first 3 months of statin therapy and medication adherence during a 33-month follow-up period was studied. METHODS: A retrospective cohort study was conducted among enrollees in a Southeastern managed care plan who started therapy with atorvastatin, fluvastatin, lovastatin, pravastatin, or simvastatin between October 1999 and August 2001, were enrolled for > or =12 months before and > or =6 months after treatment initiation, and had at least one LDL cholesterol measurement in the year before and 4-12 weeks after the start of therapy. Patients were followed up via electronic pharmacy and medical records for up to 33 more months. The follow-up period was divided into 3-month intervals; patients were considered adherent if statin therapy was available > or =80% of the time. A generalized linear model for repeated measures quantified the association between change in LDL cholesterol at 4-12 weeks and medication adherence in subsequent intervals, adjusting for demographic, clinical, and health-service-use variables. RESULTS: The final sample consisted of 9510 patients. Medication adherence decreased significantly over time: 59%, 40%, 34%, and 21% of patients were adherent at 3, 6, 12, and 36 months, respectively. Mean +/- S.D. LDL cholesterol reduction at 12 weeks was 28.9% +/- 19.9%. The relative LDL cholesterol reduction at 12 weeks was significantly and independently associated with subsequent medication adherence: Compared with subjects in the first quartile of LDL cholesterol reduction, those in quartiles 2, 3, and 4 were more likely to be adherent in any subsequent interval (adjusted odds ratio [95% confidence interval], 1.26 [1.12-1.42], 1.25 [1.11-1.40], and 1.15 [1.02-1.29], respectively). Other independent predictors of adherence in months 4-36 included adherence during the initial three months of therapy, age, and recent history of coronary revascularization. CONCLUSION: Greater reduction in LDL cholesterol levels during the first three months of statin therapy was associated with greater adherence to lipid-lowering drug therapy.

Differences in hypoglycemia event rates and associated cost-consequence in patients initiated on long-acting and intermediate-acting insulin products.

OBJECTIVE: To compare hypoglycemia event rates in patients initiated on long-acting insulin analog (glargine) or intermediate-acting insulin (NPH) and to analyze the associated cost-consequence from a managed care perspective. STUDY DESIGN: A retrospective analysis of pharmacy and medical claims and electronic laboratory result data using a southeastern United States managed care health plan. METHODS: Patients newly initiated on glargine or NPH between July 1, 2000 and August 31, 2002 were included. Hypoglycemia events were identified from medical claims by their ICD-9CM codes. Multivariable techniques were used to compare hypoglycemia event rates between cohorts. RESULTS: A total of 1434 patients were eligible (glargine = 310, NPH = 1124). The mean age was 53 years +/- 17 years and 51% of patients were male. The mean treatment duration was 8.6 months +/- 4.5 months. Multivariate analyses showed that patients in the NPH group had a higher hypoglycemia event rate than the glargine group (18.3 versus 7.3 per 100 patients per year; p = 0.009). The number needed to treat (glargine versus NPH) to avoid one hypoglycemia event per patient per year was nine patients at an A1C of 7%. The mean annual index medication cost was $47 more for glargine ($390) than for NPH ($343) per patient per year (p = 0.042). The mean cost per hypoglycemia event was $1087 (95% CI: $764-$1409). CONCLUSIONS: Patients treated with glargine had significantly lower hypoglycemia event rates compared to the NPH group. The risk difference indicated that one hypoglycemia event would be avoided for every nine patients treated with glargine instead of NPH. The cost increase associated with treating nine patients with glargine rather than NPH is less than the cost of treating one hypoglycemia event. In this population, the savings associated with reduced hypoglycemic events more than offset the increased acquisition cost associated with glargine.

Management patterns and outcomes of patients with venous thromboembolism in the usual community practice setting.

OBJECTIVE: The objectives of this study were to observe a commercially insured sample diagnosed with a venous thromboembolism (VTE) event and treated postevent with warfarin and to detail the thromboembolic and bleeding outcomes in the time periods during warfarin therapy and after discontinuation of such therapy. METHODS: This retrospective, observational cohort study used medical, pharmacy, and eligibility data from 2 US health plans. Study inclusion required an inpatient diagnosis of deep venous thrombosis (DVT) or pulmonary embolism (PE) between January 1, 1998, and December 31, 2000; warfarin, heparin, or low-molecular-weight heparin within 30 days after diagnosis; no VTE diagnosis; and no anticoagulant use for 3 months preceding diagnosis. A random sample of medical charts was abstracted to validate VTE events and collect prothrombin time/international normalized ratio (INR) result data. Recurrent VTE events, bleeding events, and proportion of time within INR range were captured in the postindex VTE event time period. Univariate and multivariate statistical techniques were used to assess outcomes. RESULTS: A total of 2,090 patients were identified with a newly diagnosed VTE event (DVT only, 1450; PE with or without DVT, 640). Mean (SD) age was 61.7 (16) years; mean (SD) follow-up time after the index diagnosis was 21.3 (10) months. Overall mean (SD) length of warfarin therapy was 6.6 (6) months. During the follow-up period, 224 patients (10.7%) experienced a recurrent VTE event and 122 patients (5.8%) experienced a bleeding event requiring hospitalization. The cumulative incidence of recurrent VTE events over 3 and 6 months was 9.0% and 10.9%, respectively. Using the chart abstraction subset, patients were within the appropriate INR range 37.7% of the time while receiving warfarin. CONCLUSIONS: Negative outcomes associated with warfarin therapy-recurrent VTE events and bleeding requiring hospitalization-were experienced by 10.7% and 5.8% of patients, respectively. These data suggest that negative outcomes may be more prevalent in usual community medical practice compared with rates observed in the controlled environment of the clinical trial or specialized anticoagulation clinic.

Follow-up lipid tests and physician visits are associated with improved adherence to statin therapy.

INTRODUCTION AND OBJECTIVE: The National Cholesterol Education Program recommends regular physician follow-up and lipid testing to promote adherence with lipid-lowering medications. The objective of this study was to determine whether lipid tests and physician visits after treatment initiation are indeed associated with adherence to statin therapy. SUBJECTS AND METHODS: A retrospective cohort study was conducted among 19 422 enrolees in a US managed care plan who initiated treatment with a statin between October 1999 and August 2001. Computerised pharmacy, medical and laboratory records were used to study the patterns and predictors of adherence with lipid-lowering therapy for up to 3 years. Adherence was assessed in 3-month intervals with patients considered 'adherent' if > or = 80% of days were covered by lipid-lowering therapy. RESULTS: In the first 3 months, 40% of patients had follow-up lipid tests and only 21% had dyslipidaemia visits (14% had both). Those receiving such care were substantially more likely to be adherent in subsequent intervals. Compared with those without follow-up, the relative odds of adherence were 1.42 and 1.27 for patients with one or more lipid test and one or more dyslipidaemia visit, respectively (95% confidence intervals [CI] 1.33, 1.50 and 1.16, 1.39). Patients who received a follow-up visit and lipid test were 45% more likely to be adherent (95% CI 1.34, 1.55). Similar associations were observed when lipid tests and dyslipidaemia visits occurred later in therapy. CONCLUSION: Early and frequent follow-up by physicians--especially lipid testing--was associated with improved adherence to lipid-lowering therapy. A randomised prospective study is needed to determine whether this relationship is causal.