Effectiveness and Safety of Apixaban, Low-Molecular-Weight Heparin, and Warfarin among Venous Thromboembolism Patients with Active Cancer: A U.S. Claims Data Analysis.

BACKGROUND: This study primarily evaluates the risk of recurrent venous thromboembolism (VTE) and major bleeding (MB) among patients with VTE and active cancer prescribed apixaban, low-molecular-weight heparin (LMWH), or warfarin, with claims data. METHODS: Four U.S. commercial insurance claims databases were used to identify patients with VTE and active cancer who initiated apixaban, LMWH, or warfarin within 30 days following the first VTE event. Stabilized inverse-probability treatment weighting (IPTW) was used to balance treatment cohorts. Cox proportional hazard models were used to evaluate risk of recurrent VTE and MB. RESULTS: All eligibility criteria were fulfilled by 3,393 apixaban, 6,108 LMWH, and 4,585 warfarin patients. After IPTW, all patient characteristics were balanced. When the follow-up was censored at 6 months, apixaban patients had a lower risk of recurrent VTE (hazard ratio [HR]: 0.61; 95% confidence interval [CI]: 0.47-0.81) and MB (HR: 0.63; 95% CI: 0.47-0.86) versus LMWH. Apixaban patients had a lower risk of recurrent VTE (HR: 0.68; 95% CI: 0.52-0.90) and similar risk of MB (HR: 0.73; 95% CI: 0.53-1.00) versus warfarin. Warfarin patients had a similar risk of recurrent VTE (HR: 0.91; 95% CI: 0.72-1.15) and MB (HR: 0.87; 95% CI: 0.68-1.12) versus LMWH. The trends were similar for the entire follow-up; however, apixaban patients had a lower risk of MB versus warfarin patients. CONCLUSION: Patients with VTE and active cancer who initiated apixaban had a lower risk of recurrent VTE and MB compared with LMWH patients. Apixaban patients also had a lower risk of recurrent VTE compared with warfarin patients.

Bleeding and recurrent VTE with apixaban vs warfarin as outpatient treatment: time-course and subgroup analyses.

In the phase 3 trial Apixaban for the Initial Management of Pulmonary Embolism and Deep-Vein Thrombosis as First-Line Therapy, apixaban was noninferior to enoxaparin, overlapped and followed by warfarin, in the treatment of venous thromboembolism (VTE) with significantly less bleeding; in a real-world evaluation, risks for bleeding and recurrent VTE were lower with apixaban vs warfarin plus parenteral anticoagulant (PAC) bridge therapy. The present study extends this research by comparing outcomes over time and within selected subgroups. A retrospective observational cohort design and 4 US private health care claims databases were used. Study population included patients who initiated outpatient treatment with apixaban or warfarin (plus PAC bridge therapy) for VTE. Major bleeding, clinically relevant nonmajor (CRNM) bleeding, and recurrent VTE were compared during the 180-day follow-up period, at selected follow-up time points (days 21, 90, 180), and within subgroups (pulmonary embolism [PE] with or without deep vein thrombosis [DVT], DVT only, provoked VTE, unprovoked VTE) using multivariable shared frailty models. Study population consisted of 20 561 apixaban patients and 35 080 warfarin patients; baseline characteristics were comparable. Overall, at selected follow-up time points, and within the aforementioned subgroups, adjusted risks were lower among apixaban vs warfarin patients: major bleeding, by 27% to 39%, CRNM bleeding, by 17% to 28%, and recurrent VTE, by 25% to 39% (all P ≤ .01). In this real-world study of VTE patients, risks of bleeding and recurrent VTE were lower among apixaban (vs warfarin) patients during the 180-day follow-up period, at selected follow-up time points, and within subgroups defined by index VTE episode.

Cost-Effectiveness of Extended and One-Time Screening Versus No Screening for Non-Valvular Atrial Fibrillation in the USA.

BACKGROUND: There is limited evidence on the clinical and cost benefits of screening for atrial fibrillation (AF) with electrocardiogram (ECG) in asymptomatic adults. METHODS: We adapted a previously published Markov model to evaluate the clinical and economic impact of one-time screening for non-valvular AF (NVAF) with a single 12-lead ECG and a 14-day extended screening with a hand-held ECG device (Zenicor single-lead ECG, Z14) compared with no screening. Clinical events considered included ischemic stroke, systemic embolism, major bleeds, myocardial infarction, and death. Epidemiology and effectiveness data for extended screening were from the STROKESTOP study. Risks of clinical events in NVAF patients were derived from ARISTOTLE. Analyses were conducted from the perspective of a third-party payer, considering a population with undiagnosed NVAF, aged 75 years in the USA. Costs and utilities were discounted at a 3% annual rate. Parameter uncertainty was formally considered via deterministic and probabilistic sensitivity analyses (DSA and PSA). Structural uncertainty was assessed via scenario analyses. RESULTS: In a hypothetical cohort of 10,000 patients followed over their lifetimes, the number of additional AF diagnoses was 54 with 12-lead ECG and 255 with Z14 compared with no screening. Both screening strategies led to better health outcomes (ischemic strokes avoided: ECG 12-lead, 9.8 and Z14, 42.2; quality-adjusted life-years gained: ECG 12-lead, 31 and Z14, 131). Extended screening and one-time screening were cost effective compared with no screening at a willingness-to-pay (WTP) threshold of $100,000 per QALY gained ($58,728/QALY with ECG 12-lead and $47,949/QALY with Z14 in 2016 US dollars). ICERs remained below $100,000 per QALY in all DSA, most PSA runs, and in all scenario analyses except for a scenario assuming low anticoagulation persistence. CONCLUSIONS: Our analysis suggests that, screening the general population at age 75 years for NVAF is cost effective at a WTP threshold of $100,000. Both extended screening and one-time screening for NVAF are expected to provide health benefits at an acceptable cost.

Systematic review of societal costs associated with stroke, bleeding and monitoring in atrial fibrillation.

Aim: Economic consequences associated with the rise in nonvitamin K antagonist oral anticoagulant use on a societal level remain unclear. Materials & methods: Evidence from the past decade on the societal economic burden associated with stroke, bleeding and international normalized ratio monitoring in atrial fibrillation was collected and summarized through a systematic literature review. Results: There were 14 studies identified that reported indirect costs, which were highest among patients with hemorrhagic stroke and intracranial hemorrhage. The contribution of indirect costs to the total was marginal during acute treatment but substantially increased (30-50%) 2 years after stroke and bleeding events. Conclusion: Limited data were available on societal costs in atrial fibrillation and further research is warranted.

Hospital Resource Utilization and Costs Associated With Warfarin Versus Apixaban Treatment Among Patients Hospitalized for Venous Thromboembolism in the United States.

A real-world US database analysis was conducted to evaluate the hospital resource utilization and costs of patients hospitalized for venous thromboembolism (VTE) treated with warfarin versus apixaban. Additionally, 1-month readmissions were evaluated. Of 28 612 patients with VTE identified from the Premier Hospital database (August 2014-May 2016), 91% (N = 26 088) received warfarin and 9% (N = 2524) received apixaban. Outcomes were assessed after controlling for key patient/hospital characteristics. For index hospitalizations, the average length of stay (LOS) was longer (3.8 vs 3.1 days, P < .001; difference: 0.7 days) and mean hospitalization cost higher (US$3224 vs US$2,740, P < .001; difference: US$484) for warfarin versus apixaban-treated patients. During the 1-month follow-up period, warfarin treatment was associated with a greater risk of all-cause readmission (odds ratio [OR]: 1.27; 95% confidence interval [CI]: 1.09-1.48, P = .003), major bleeding (MB)-related readmission (OR: 2.10; 95% CI: 1.03-4.27, P = .04), and any bleeding-related readmission (OR: 1.67; 95% CI: 1.09-2.56, P = .02) versus apixaban. The results of this real-world analysis show that compared to warfarin, apixaban treatment was associated with shorter index hospital stays, lower index hospitalization costs, and reduced risk of MB-related readmissions among hospitalized patients with VTE.

Effectiveness and Safety of Apixaban versus Warfarin as Outpatient Treatment of Venous Thromboembolism in U.S. Clinical Practice.

In the AMPLIFY clinical trial, apixaban was non-inferior to warfarin plus subcutaneous enoxaparin bridge therapy in the treatment of acute venous thromboembolism (VTE) and was associated with significantly less bleeding. This study evaluated their comparative effectiveness and safety in routine clinical practice. A matched-cohort design and data from four U.S. private health care claims databases were employed. Study population comprised patients who initiated outpatient treatment with apixaban versus warfarin (plus parenteral anticoagulant bridge therapy) within 30 days of their initial VTE episode; apixaban and warfarin patients were matched on age, characteristics of VTE episode, study database and propensity score. Major bleeding, clinically relevant non-major (CRNM) bleeding and recurrent VTE during the 180-day (maximum) follow-up period were compared using shared frailty models. During mean follow-up of 143 days among apixaban patients (n = 17,878) and 152 days among warfarin patients (n = 17,878), incidence proportions for apixaban versus warfarin, respectively, were 1.7% versus 2.3% for major bleeding, 7.0% versus 9.4% for CRNM bleeding and 2.3% versus 2.9% for recurrent VTE. In shared frailty models, risks of major bleeding (hazard ratio [HR] = 0.75, 95% confidence interval [CI] = 0.64-0.87), CRNM bleeding (HR = 0.77, 95% CI = 0.71-0.83) and recurrent VTE (HR = 0.80, 95% CI = 0.70-0.91) were lower for apixaban versus warfarin. In this large-scale evaluation of VTE patients receiving outpatient treatment with apixaban or warfarin in U.S. clinical practice, risks of major bleeding, CRNM bleeding and recurrent VTE were significantly lower among patients who received apixaban.

Daclatasvir combined with asunaprevir is a cost-effective and cost-saving treatment for hepatitis C infection in China.

Aim: To evaluate the cost-effectiveness of the novel all-oral direct-acting antiviral regimen daclatasvir + asunaprevir (DUAL), versus interferon-based regimens for the treatment of chronic hepatitis C virus genotype 1b infection. Methods: Inputs for a lifetime Markov model were sourced from clinical trials and published literature. Outputs include disease management costs, life expectancy, quality-adjusted life-years and cost-effectiveness. Sensitivity analyses assessed the drivers of cost-effectiveness and sustained virologic response thresholds at which DUAL is cost-saving. Results: DUAL was associated with discounted incremental quality-adjusted life-years of 1.29-3.85 and incremental life-years of 0.85-2.59 per patient, with discounted lifetime cost savings of USD$1415-8525. Associated sustained virologic response rates could fall to 45.1-84.8%, while remaining dominant. Conclusion: Treatment with DUAL provides significant clinical benefit, while accruing lower lifetime costs.

Assessing the Budget Impact and Economic Outcomes of the Introduction of Daclatasvir + Asunaprevir and Sofosbuvir/Ledipasvir for the Treatment of Chronic Hepatitis C Virus Infection in Japan.

BACKGROUND: The advent of highly efficacious, well-tolerated, all-oral direct-acting antiviral regimens has revolutionized the standard of care for patients chronically infected with hepatitis C virus. As efficacy and safety rates converge, prescribers and payers need to consider value for money. OBJECTIVES: To evaluate the health economic value of daclatasvir + asunaprevir versus sofosbuvir/ledipasvir via a cost-effectiveness analysis, and determine the optimal treatment considering both costs and health outcomes in Japan. METHODS: A previously published Markov model was used to estimate the cost-effectiveness of daclatasvir + asunaprevir compared with sofosbuvir/ledipasvir on the basis of a matching-adjusted indirect comparison of pivotal trials and modeling inputs specific to the Japanese setting. A de novo budget impact model was developed and used to predict the cost implications of differing treatment sequences. RESULTS: Cost-effectiveness results demonstrated minimal difference in terms of benefit (0.037 fewer QALYs and 0.014 fewer life-years with daclatasvir + asunaprevir); nevertheless, a significant difference in cost was predicted (estimated ¥2,299,700 [US $21,695] reduction with daclatasvir + asunaprevir). The budget impact analysis estimated that treatment with daclatasvir + asunaprevir is expected to be less expensive than treatment with sofosbuvir/ledipasvir (as the proportion of patients initially treated with sofosbuvir/ledipasvir increased from 0% to 100%, total costs increased from ¥206 to ¥403 billion [US $1.94 billion to US $3.80 billion]). CONCLUSIONS: On the basis of results from an established cost-effectiveness model and a conventional budget impact analysis, treatment with daclatasvir + asunaprevir is expected to be cost-saving compared with treatment with sofosbuvir/ledipasvir in Japan with similar health outcomes, regardless of treatment sequence.

Daclatasvir + asunaprevir versus sofosbuvir/ledipasvir for hepatitis C genotype 1 in Japanese patients: an indirect comparison.

AIM: To compare daclatasvir + asunaprevir (DCV + ASV) versus sofosbuvir/ledipasvir (SOF/LDV) for hepatitis C virus genotype 1b in Japanese patients without NS5A polymorphisms at L31 and Y93H. PATIENTS & METHODS: All Phase III trials of SOF/LDV and DCV + ASV conducted in Japan were included. To adjust for cross-trial differences, DCV + ASV patients were weighted to match reported SOF/LDV summary baseline characteristics. RESULTS: After adjustment, the rate of SVR12 (99.3 vs 100%; p = 0.398) and discontinuation due to adverse events (1.3 vs 0.0%; p = 0.327) were similar between patients treated with DCV + ASV (n = 252) and SOF/LDV (n = 171). CONCLUSION: After adjusting for cross-trial differences in baseline characteristics, DCV + ASV and SOF/LDV were associated with similar efficacy and discontinuation due to adverse events in the treatment of hepatitis C virus genotype 1b in Japanese patients without NS5A polymorphisms.

A systematic review and mixed-treatment comparison of dapagliflozin with existing anti-diabetes treatments for those with type 2 diabetes mellitus inadequately controlled by sulfonylurea monotherapy.

BACKGROUND: To compare the first-in-class sodium glucose co-transporter 2 (SGLT2) inhibitor, dapagliflozin, with existing type 2 diabetes mellitus (T2DM) treatment options available within the European Union (EU) for add-on therapy to sulfonylureas (SUs). METHODS: A systematic review was conducted to identify randomised controlled trials (RCTs) in T2DM patients inadequately controlled by SU monotherapy. Direct meta-analysis, Bucher indirect comparisons and Bayesian network meta-analysis (NMA) were conducted on studies meeting predefined inclusion criteria. Sufficient data were available to assess three clinical endpoints at 24 (+/- 6) weeks follow-up: mean change in HbA1c from baseline, mean change in weight from baseline, and the proportion of patients experiencing at least one episode of hypoglycaemia. The effect of confounding baseline factors was explored through covariate analyses. RESULTS: The search identified 1,901 unique citations, with 1,870 excluded based on title/abstract. From reviewing full-texts of the remaining 31 articles, 5 studies were considered eligible for analysis. All studies were comparable in terms of baseline characteristics, including: HbA1c, age and body mass index (BMI). In addition to dapagliflozin, sufficient data for meta-analysis was available for three dipeptidyl peptidase-4 (DPP-4) inhibitors and one glucagon-like peptide-1 (GLP-1) analogue. Based on fixed-effect NMA, all treatment classes resulted in statistically significant decreases in HbA1c at follow-up compared to placebo. Dapagliflozin treatment resulted in significantly decreased weight at follow-up compared to placebo (-1.54 kg; 95% CrI -2.16, -0.92), in contrast to treatment with GLP-1 analogues (-0.65 kg; 95% CrI -1.37, 0.07) and DPP-4 inhibitors (0.57 kg; 95% CrI 0.09, 1.06). The odds of hypoglycaemia were similar to placebo for dapagliflozin and DPP-4 inhibitor add-on treatment, but significantly greater than placebo for GLP-1 analogue add-on treatment (10.89; 95% CrI 4.24, 38.28). Assessment of NMA model heterogeneity was hindered by the small size of the network. CONCLUSIONS: Dapagliflozin, DPP-4 inhibitors and GLP-1 analogues, in combination with SU, all provided better short-term glycaemic control compared to SU monotherapy. Dapagliflozin was the only add-on therapy that had both a favourable weight and hypoglycaemia profile compared to the other classes of treatment evaluated.

Impact of adherence and weight loss on glycemic control in patients with type 2 diabetes: cohort analyses of integrated medical record, pharmacy claims, and patient-reported data.

BACKGROUND: Managed care organizations put great effort into managing the population of patients with type 2 diabetes mellitus (T2DM) because of the health and economic burden of this disease. In patients with T2DM, weight loss and glycemic control are primary treatment aims to help improve patient outcomes, but these goals are not easily achieved. While achieving these aims requires a multifaceted approach of drug therapy management and lifestyle modification, truly understanding the role of medication adherence in achieving these outcomes is important for both patient and population management. This study expands on existing evidence that weight loss is associated with improved glycemic control by examining the role of medication adherence in achieving these goals in a managed care setting. This study is unique in that these associations are evaluated using multiple sources of data, including medical records for treatment outcomes, pharmacy claims, and patient-reported data to assess medication adherence. These data sources represent those typically available to payers or providers.  OBJECTIVE: To describe the relationships between medication and adherence, weight change, and glycemic control in patients with T2DM. METHODS: This historical cohort study included adult patients with T2DM in a large integrated health system and was based on electronic health record and pharmacy claims data from November 1, 2010, through October 31, 2011, as well as data from a self-reported adherence survey conducted in March 2012. Included patients received a diabetes medication from a therapeutic class not previously received, between November 1, 2010, and April 30, 2011 (index date), who had blood glucose (HbA1c) and weight values at index date and 6 months follow-up, participated in an adherence survey, and had ≥ 1 prescription claim for the index-date drug. Associations between the dual outcomes of weight loss (≥ 3%) and HbA1c control ( less than 7.0%), while controlling for medication adherence and other demographic, treatment, and clinical variables, were evaluated using structural equation models (SEM). Separate models adjusted for different measures of medication adherence-self-reported using the 5-item Medication Adherence Rating Scale (MARS-5) and a modified medication possession ratio (mMPR) from pharmacy claims data. RESULTS: The study included 166 patients with a mean age of 61.1 (standard deviation = 12.1) years; 56.0% were female. Medication adherence was high, with 72.2% adherent using MARS-5 and 77.1% using mMPR measures. The SEMs found that only self-reported medication adherence is associated with weight loss (MARS-5: OR = 1.70, 95% CI = 1.11-2.60), while both self-reported and claims-based medication adherence were associated with HbA1c less than 7.0% (MARS-5: OR = 1.59, 95% CI = 1.09-2.34; mMPR: OR 2.71, 95% CI = 1.22-5.98). Further, weight loss is significantly associated with HbA1c less than 7.0% (MARS-5: OR = 3.60, 95% CI = 2.39-5.46; mMPR: OR 2.99, 95% CI = 1.45-6.17). CONCLUSIONS: This study has provided additional evidence in a managed, integrated setting that in patients treated for T2DM, weight loss is associated with good glycemic control. Adherence is associated with weight loss according to self-report, but not claims-based adherence measures. Adherence is also associated with glycemic control as measured by the 2 different methods. This study adds to the body of literature highlighting the importance of adherence as well as weight loss in achieving good glycemic control. The fact that the association of weight loss and adherence on glycemic control outcomes was significant regardless of medication adherence method is important in payer-provider collaborations, where access to data sources to evaluate adherence may vary. This study also supports continued investment in weight loss and adherence programs in the management of patients with T2DM.

Risk factors for cardiovascular events and bleeding complications following non-cardiac surgery or procedure in patients with drug eluting stent placement.

OBJECTIVES: Previous studies suggest an increased incidence of cardiovascular (CV) events after P2Y12 receptor blocker cessation. The aim of this study was to examine the effect of P2Y12 receptor blocker cessation and other risk factors on the risk of CV events and bleeding events after non-cardiac surgery/procedure in patients with drug-eluting stents (DES). DESIGN: Retrospective cohort study. SETTING: Single large healthcare system in the northeast of the USA. PATIENTS: All adult patients who had a coronary drug eluting stent (DES) placed between 2002 and 2007 in our institution. INTERVENTIONS: No randomised intervention. The principal exposure was cessation of P2Y12 receptor blocker. METHODS: This was a retrospective study of all adult patients who had a coronary DES placed between 2002 and 2007 in our institution. We considered all non-cardiac procedures up to 1 year after DES placement. Generalised estimating equations were used to identify the independent risk factors. Multiple imputations were used to replace missing values. MAIN OUTCOME MEASURES: The outcomes were CV events including death from any cause and bleeding, occurring within 30 days after the procedure. RESULTS: From 2002 to 2007, 6397 patients had DES, 873 (13.6%) had at least one non-cardiac procedure. A total of 3.6% (33/927) of the admissions were complicated by at least one cardiovascular event and 6.9% (55/795) were complicated by bleeding. Urgent procedure (versus elective) was the only independent risk factor for CV events (OR=4.82, 95% CI 1.95 to 11.89). Older age, diabetes, urgent procedures, orthopaedic and vascular surgery compared to unclassified surgery were independent risk factors for bleeding. CONCLUSIONS: Non-cardiac procedures are common within 1 year after DES placement. Urgent nature of procedure is a risk factor for CV events and bleeding complications. Older age, diabetes, type of surgery, are risk factors associated only with bleeding events.

Comparison of demographic factors and cardiovascular risk factor control among U.S. adults with type 2 diabetes by insulin treatment classification.

AIMS: Data on glucose and cardiovascular disease (CVD) risk factor control among persons with type 2 diabetes mellitus (DM) according to insulin treatment status are lacking. We examined DM control, risk factors, and comorbidities among U.S. persons according to insulin treatment status. METHODS: In the U.S. National Health and Nutrition Examination Surveys 2003-2006, we examined in 10,637 adults aged ≥30 with type 2 DM the extent of control of A1c, LDL-C, HDL-C, triglycerides, and blood pressure (BP) and composite goal attainment by insulin use status. RESULTS: 6.6% (n=889, projected to 14.3 million) had type 2 DM; of these, 22.9% were insulin users and 57.2% were treated only by other diabetes medications. Overall, 58.2% had an A1c<7% (53 mmol/mol) (insulin users 33.1%, non-insulin treated 66.1%, and 77.9% of those not on medication, p<0.0001). Overall, 44.2% were at a BP goal of <130/80 mmHg, 43.8% had an LDL-C<100 mg/dl (2.6 mmol/L), and 13.9% a BMI<25 kg/m(2). Only 10.2% were simultaneously at A1c, LDL, and BP goals (5.4% of those on insulin). CONCLUSIONS: U.S. adults with type 2 DM, especially those treated with insulin remain inadequately controlled for A1c and CVD risk factors and have a high prevalence of comorbidities.

Global cardiovascular disease risk assessment in United States adults with diabetes.

BACKGROUND: Diabetes mellitus (DM) is often considered a risk equivalent for cardiovascular disease (CVD); however, the variation in CVD risk in adults with DM has not been described. METHODS: We studied 1114 US adults aged ≥18 years with DM from national survey data and the proportion at low (<10%), intermediate (10-20%) and high (>20%) risk, or with CVD, by age, gender, ethnicity and diabetes type and treatment, and glycaemic and risk factor control by risk group. RESULTS: Overall, 22.9% were low, 17.5% intermediate, 31.4% high risk and 28.2% had pre-existing CVD (total 59.6% high risk/CVD). More Hispanics (32.4%) and Blacks (30.6%) versus Whites (18.8%) were at lower risk (p<0.0001). Among type 1 versus 2 DM, 35% vs. 65% (p<0.0001) and among insulin users 68.1% were high risk or with CVD. However, among low-intermediate risk, >50% have metabolic syndrome and 7% chronic kidney disease, increasing the high risk/CVD group to 86.8%. Simultaneous achievement of HbA1c, blood pressure and low density lipoprotein-cholesterol goals was low (<15%) regardless of risk group. CONCLUSIONS: Many DM patients are not at high 10-year CVD risk, but metabolic factors may place them at greater long-term risk. Risk assessment could help target the intensity of treatment.

Incidence of death and recurring acute coronary syndrome after stopping clopidogrel therapy in a large commercially-insured population in the US.

BACKGROUND/OBJECTIVE: Guidelines support clopidogrel therapy in medically-treated or percutaneous coronary intervention (PCI) patients after hospitalization for acute coronary syndrome (ACS). However, clopidogrel discontinuation has been associated with increased short-term risks. This study evaluated the risk of adverse outcomes (AOs), defined as death or recurrent ACS, after clopidogrel discontinuation in a managed-care population. METHODS: ACS patients (n = 7625) with ≥1 clopidogrel pharmacy claim from 2001 to 2006 and no AO before discontinuing clopidogrel were identified from administrative claims data. AO occurrences were recorded at 90-day intervals following clopidogrel discontinuation. RESULTS: The mean (SD) duration of clopidogrel therapy for medically-treated, bare metal stent (BMS) and drug eluting stent (DES) patients was 349.2 (393.1) days, 235.6 (383.0) days, and 280.2 (227.1) days, respectively. Among medically-treated patients, Poisson regression analysis showed a 2.19 times higher AO risk (p < 0.01), a 1.63 times greater risk among BMS patients (p < 0.01), and a 1.56 times greater risk for DES patients (p ≥ 0.05) during days 0-90 versus days 91-180 after clopidogrel discontinuation. Sensitivity analysis showed that medically-treated, BMS and DES patients with ≤90 days of clopidogrel therapy had 2.13, 1.68 and 2.40 times higher AO risk, respectively, during days 0-90 versus 91-180 after discontinuation. No significant elevated AO risk was observed after discontinuation in patients on clopidogrel for 91-270 days. Limitations included those associated with the use of administration claims date, the absence of clinical data and lack of knowledge of aspirin use. CONCLUSIONS: Patients who discontinued clopidogrel therapy were at high risk of death or recurrent ACS during the first 90 days. AO risks following discontinuation appeared elevated in patients with ≤90 days of clopidogrel therapy versus those with >90 days of treatment.

One-year costs of ischemic heart disease among patients with acute coronary syndromes: findings from a multi-employer claims database.

OBJECTIVE: Acute coronary syndromes (ACS) are life-threatening disorders requiring intensive medical management or invasive cardiovascular procedures. Limited data exist on the costs and resource utilization associated with ACS. METHODS: This retrospective single-cohort study analyzed administrative claims data from employer-sponsored plans for patients with an ACS hospitalization in 2001-2002. A 1-year follow-up period was used, and patients who were under age 35 or had an ACS diagnosis in the 12 months before the hospitalization were excluded. Costs were reported in 2005 US dollars. RESULTS: We identified 16,321 patients hospitalized for ACS during the study period. Mean (+/- SD) age was 55.6 (+/- 6.7) years, 66.7% were male, and 46.3% underwent a revascularization procedure during their initial hospitalization. Mean length of stay for the initial hospitalization was 4.6 days (median: 3.0; IQR: 2.0-5.0), and per-patient expenditures averaged $22,921 (median: $13,960; IQR: $6839-28 588). During the follow-up period, 21% of patients were rehospitalized for ischemic heart disease (IHD), and the cost of rehospitalization averaged $28,637. Additionally, in the year following the inpatient admission, 50% of patients were prescribed antiplatelet or anticoagulant medications, and 90% of patients were prescribed lipid-lowering, antihypertensive, or antiarrhythmic medications. IHD-related expenditures after the initial inpatient stay averaged $9425 (median: $2800; IQR: $899-7577); 61% of these costs were due to rehospitalization. Total first-year costs averaged $32,345 (median: $21,653; IQR: $10,642-41,106). LIMITATIONS: Diagnoses could not be verified through medical charts. Payments for Medicare patients were not assessed given our focus on the working-age population. CONCLUSIONS: In this employer-sponsored health plan population, the costs of inpatient and outpatient IHD-related care were high. Future studies should evaluate the impact of improved patient management on post-discharge costs.

Quality of anticoagulation monitoring in nonvalvular atrial fibrillation patients: comparison of anticoagulation clinic versus usual care.

BACKGROUND: Prior research suggests that receiving specialized anticoagulation services enables patients to achieve better clinical outcomes. OBJECTIVE: To assess the quality of anticoagulation therapy in patients with atrial fibrillation who were enrolled in an anticoagulation clinic (ACC) versus usual care (UC). METHODS: Using Sharp Rees-Stealy physician group claims data, we estimated time spent in therapeutic range and time to first major bleeding episode or stroke for ACC and UC patients. t-Tests were used to compare time in therapeutic range proportions, and Kaplan-Meier survival analysis was performed to compare rates of bleeding and stroke between groups. RESULTS: We identified 1107 patients (351 ACC, 756 UC) treated with anticoagulation therapy for atrial fibrillation with more than one international normalized ratio (INR) reported between March 2001 and March 2004. ACC patients spent a greater proportion (68.14%) of time in therapeutic range compared with UC patients (42.07%; p < 0.001). There was a significant difference between groups in average time between INR tests (ACC = 14.31 days, UC = 18.39 days; p < 0.001). ACC patients were 59% less likely to experience a bleed following the index date than were UC patients (HR = 0.41; 95% CI 0.2444 to 0.6999; p = 0.001), but type of care was not a significant predictor for stroke (HR = 0.95; 95% CI 0.5125 to 1.7777; p value NS). CONCLUSIONS: Results from this observational study reinforce the positive impact that anticoagulation services have on anticoagulation therapy outcomes, emphasizing the importance of providing such services for patients undergoing treatment with warfarin.

Quality of clinical documentation and anticoagulation control in patients with chronic nonvalvular atrial fibrillation in routine medical care.

OBJECTIVE: Anticoagulation quality and record documentation were retrospectively assessed in patients with chronic nonvalvular atrial fibrillation (CNVAF) managed in a routine care setting. METHODS: Medical record data extraction from physician practices in 4 regions of the United States. RESULTS: Of 686 patients, 59% had an electrocardiogram confirming CNVAF, 84% listed at least 1 stroke risk factor, and 60% indicated the goal target international normalized ratio (INR). Two thirds of INRs>3.0 or <2.0 had no recorded dose change, nor did 45% of INRs>5.0. Vitamin K was given (3%) or anticoagulation was temporarily discontinued (9%) for INRs>5.0. The median interval of INR testing was 21 days, which decreased to 7 days for INRs> 4.60. Patients spent 58% of the time in therapeutic range. CONCLUSION: Serious deficiencies in quality and documentation of routine medical care of anticoagulation for patients with CNVAF continue to exist.

Warfarin exposure and the risk of thromboembolic and major bleeding events among medicaid patients with atrial fibrillation.

BACKGROUND: Outcomes of anticoagulation have been assessed in commercially insured populations, but similar data do not exist for Medicaid populations. OBJECTIVE: To assess the association between warfarin exposure and rates of thromboembolic and bleeding events among patients with nonvalvular atrial fibrillation (NVAF) enrolled in California Medicaid. METHODS: Using a retrospective cohort design based on administrative claims data, we selected Medicaid enrollees aged 50 years and older based on their first claim with a diagnosis of AF between January 1, 1998, and March 31, 2002. Patients were excluded if they had selected contraindications to warfarin, claims for valve replacement procedures, or evidence that AF resulted from transient or reversible causes. Pharmacy claims and prothrombin time tests were used to define subsequent periods of warfarin use (exposure) and nonuse (nonexposure) by all patients. The relative rates of hospitalization for thromboembolic and bleeding events associated with periods of warfarin exposure versus nonexposure were estimated. RESULTS: The 4355 study patients had a mean age of 74 years, and 65% were female. Fifty-nine percent filled any prescriptions for warfarin following AF diagnosis. Across all patients, warfarin exposure occurred during 37% of days after diagnosis. Thromboembolic events were 27% less frequent during periods of warfarin exposure relative to periods of non-exposure (p < 0.01). Major bleeding events were not significantly more common during periods of warfarin exposure (p = 0.55). CONCLUSIONS: In this Medicaid population with NVAF, warfarin use was low and was associated with a relatively modest reduction in thromboembolic events, with no increase in major bleeding risk.