Use of Statewide Administrative Data to Assess Clinical Outcomes: A Retrospective Cohort Study of Therapeutic Anticoagulation for Isolated Calf Vein Thrombosis.

BACKGROUND: Single-center comparative effectiveness studies evaluating outcomes that can occur posthospitalization may become biased if outcomes diagnosed at other facilities are not ascertained. Administrative datasets that link patients' records across facilities may improve outcome ascertainment. OBJECTIVE: To determine whether use of linked administrative data significantly augments thromboembolic outcome ascertainment. RESEARCH DESIGN: Retrospective cohort study. SUBJECTS: Patients with an acute isolated calf deep vein thrombosis (DVT) diagnosed at 1 Californian center during 2010-2013. MEASURES: Proximal DVT or pulmonary embolism (PE) within 180 days. We ascertained outcomes from linked California hospitalization, emergency department, and ambulatory surgery data and compared this information to outcomes previously identified from review of the center's medical records. RESULTS: Among 384 patients with an isolated calf DVT, 333 could be linked to longitudinal administrative data records. Ten patients had a possible proximal DVT or PE (4 more clearly so) from administrative data; all were unknown from medical record review. Eleven patients with known outcomes from medical record review had no outcome from administrative data. The adjusted odds ratio of proximal DVT or PE with therapeutic anticoagulation attenuated from 0.33 [95% confidence interval (CI), 0.12-0.87] using only medical record review to 0.64 (95% CI, 0.29-1.40) using both medical record review and possible outcomes from administrative data. Restricting the outcome to diagnoses clearly involving proximal DVT or PE, the adjusted odds ratio was 0.46 (95% CI, 0.19-1.10). CONCLUSIONS: Use of linked hospital administrative data augmented detection of outcomes but imperfect linkage, nonspecific diagnoses, and documentation/coding errors introduced uncertainty regarding the accuracy of outcome ascertainment.

Cost-effectiveness of edoxaban for the treatment of venous thromboembolism based on the Hokusai-VTE study.

OBJECTIVE: Venous thromboembolism (VTE) is associated with almost 300,000 deaths per year in the United States. Novel oral anticoagulants (NOACs) offer an alternative to warfarin-based therapy without monitoring requirements and with fewer drug and food interactions. Edoxaban, a direct Xa inhibitor, is approved by the Food and Drug Administration (FDA), based upon results of the Hokusai-VTE Phase 3 trial. The trial demonstrated that edoxaban administered once daily after initial treatment with heparin was non-inferior in reducing the risk of VTE recurrence and caused significantly less major and clinically relevant non-major (CRNM) bleeding compared to warfarin. The objective of this study was to evaluate the cost-effectiveness of edoxaban versus warfarin for the treatment of adults with VTE. METHODS: A cost-effectiveness model was developed using patient-level data from the Hokusai-VTE trial, clinical event costs from real-world databases, and drug acquisition costs for warfarin of $0.36 and edoxaban of $9.24 per tablet. RESULTS: From a U.S. health-care delivery system perspective, the incremental cost-effectiveness ratio (ICER) was $22,057 per quality adjusted life year (QALY) gained. Probabilistic sensitivity analysis showed that edoxaban had an ICER <$50,000 per QALY gained relative to warfarin in 67% of model simulations. The result was robust to variation in key model parameters including the cost and disutility of warfarin monitoring. CONCLUSION: Despite its higher drug acquisition cost, edoxaban is a cost-effective alternative to warfarin for the treatment of VTE.

Do Women Have Worse Amputation-Free Survival Than Men Following Endovascular Procedures for Peripheral Arterial Disease? An Evaluation of the California State-Wide Database.

OBJECTIVES: Female gender has been shown to negatively affect the outcomes of surgical bypass for peripheral arterial disease (PAD). We examined gender-related disparities in outcomes of endovascular PAD procedures in a large population-based study. METHODS: We used discharge data from California hospitals to identify patients who had PAD interventions during 2005 to 2009. Logistic regression was used for 12-month reintervention, and Cox proportional hazard regression was used for amputation-free survival comparisons. RESULTS: A total of 25 635 patients had endovascular procedures (11 389 [44.4%] women). Women were more likely than men (34.5% vs 30.1%, P < .0001) to have critical limb ischemia (CLI). Twelve-month reintervention rate in women was similar to men. Amputation-free survival was better among women than men (hazard ratio 0.84, 95% confidence interval [CI] 0.76-0.93, P = .0006). CONCLUSION: Despite presenting more frequently with CLI, women had better amputation-free survival than men following endovascular procedures. Future research should determine whether findings favor one type of PAD treatment modality over another for women.

Racial disparities in outcomes of endovascular procedures for peripheral arterial disease: an evaluation of California hospitals, 2005-2009.

BACKGROUND: Racial/ethnic disparities in treatment outcomes of peripheral arterial disease (PAD) are well documented. Compared with non-Hispanic (NH) whites, blacks and Hispanics are more likely to undergo amputation and less likely to undergo bypass surgery for limb salvage. Endovascular procedures are being increasingly performed as first line of therapy for PAD. In this study, we examined the outcomes of endovascular PAD treatments based on race/ethnicity in a contemporary large population-based study. METHODS: We used Patient Discharge Data from California's Office of Statewide Health Planning and Development to identify all patients over the age of 35 who underwent a lower extremity arterial intervention from 2005 to 2009. A look-back period of 5 years was used to exclude all patients with prior lower extremity arterial revascularization procedures or major amputation. Cox proportional hazards regression was used to compare amputation-free survival and time to death within 365 days. Logistic regression was used for comparison of 1-month myocardial infarction, 1-month major amputation, 1-month all-cause mortality, 12-month major amputation, 12-month reintervention, and 12-month all-cause mortality rates among NH white, black, and Hispanic patients. These analyses were adjusted for age, gender, insurance status, severity of PAD, comorbidities, history of coronary artery angioplasty or bypass surgery, or history of carotid endarterectomy. RESULTS: Between 2005 and 2009, a total of 41,507 individuals underwent PAD interventions, 25,635 (61.7%) of whom underwent endovascular procedures. There were 17,433 (68%) NH whites, 4,417 (17.2%) Hispanics, 1,979 (7.7%) blacks, 1,163 (4.5%) Asian/Native Hawaiians, and 643 (2.5%) others in this group. There was a statistically significant difference in the amputation-free survival within 365 days among the NH white, Hispanic, and black groups (P < 0.0001); the hazard ratio for amputation within 365 days was 1.69 in Hispanics (95% confidence interval [CI] 1.51-1.90, P < 0.0001) and 1.68 in blacks (95% CI 1.44-1.96, P < 0.001) compared with NH whites following endovascular procedures after adjusting for age, gender, insurance status, comorbidities, severity of PAD, history of coronary artery angioplasty or bypass surgery, or history of carotid endarterectomy. After adjusting for the aforementioned confounders, the first reintervention within 12 months was also significantly associated with race/ethnicity (P = 0.002). Odds ratio for reintervention was 1.17 in blacks (95% CI 1.06-1.30, P = 0.002) and 1.084 in Hispanics (95% CI 1.00-1.16, P = 0.04) compared with NH whites. CONCLUSIONS: In this contemporary large population-based study, we demonstrated that even among matched cohorts Hispanics and blacks have worse amputation-free survival than NH whites following endovascular therapy. Our study also found that Hispanics and blacks are more likely to undergo lower extremity arterial reinterventions than NH whites. Further research is crucial in understanding if higher reintervention rates in Hispanics and blacks are because of more severe disease and/or poor access to proper follow-up care and optimal medical management.

Risk assessment models for cancer-associated venous thromboembolism.

Venous thromboembolism (VTE) is common in cancer patients, and is associated with significant morbidity and mortality. Several factors, including procoagulant agents secreted by tumor cells, immobilization, surgery, indwelling catheters, and systemic treatment (including chemotherapy), contribute to an increased risk of VTE in cancer patients. There is growing interest in instituting primary prophylaxis in high-risk patients to prevent incident (first-time) VTE events. The identification of patients at sufficiently high risk of VTE to warrant primary thromboprophylaxis is essential, as anticoagulation may be associated with a higher risk of bleeding. Current guidelines recommend the use of pharmacological thromboprophylaxis in postoperative and hospitalized cancer patients, as well as ambulatory cancer patients receiving thalidomide or lenalidomide in combination with high-dose dexamethasone or chemotherapy, in the absence of contraindications to anticoagulation. However, the majority of cancer patients are ambulatory, and currently primary thromboprophylaxis is not recommended for these patients, even those considered at very high risk. In this concise review, the authors discuss risk stratification models that have been specifically developed to identify cancer patients at high risk for VTE, and thus might be useful in future studies designed to determine the potential benefit of primary thromboprophylaxis.

Effects of race and ethnicity on the incidence of venous thromboembolism.

Although there is strong evidence that the prevalence of venous thrombo-embolism (VTE) varies significantly among different ethnic/racial groups, the genetic, physiologic and/or clinical basis for these differences remain largely undefined. African-American patients have a significantly higher rate of incident VTE, particularly following exposure to a provoking risk factor such as surgery, medical illness, trauma, etc. In addition, African-Americans are more likely to be diagnosed with pulmonary embolism (PE) than deep-vein thrombosis (DVT) compared to Caucasian and other racial groups. On the other extreme, Asians/Pacific Islanders have a 70% lower prevalence of VTE and this is true for both idiopathic VTE and provoked, or 'secondary', VTE. Hispanics have a significantly lower prevalence of VTE compared to Caucasians, but higher than Asians/Pacific Islanders. The incidence of recurrent VTE varies depending on gender, type of thromboembolic event and race. Further research is needed in order to determine the fundamental differences between racial/ethnic groups that explain the observed differences in the prevalence of VTE. Race/ethnicity should be considered an important factor in the risk-stratification of patients with suspected VTE or patients at some risk for developing VTE.

N-of-1 trials of expensive biological therapies: a third way?

In developing policies for use of expensive agents, such as those used for the treatment of rheumatoid arthritis, managed care organizations have invoked "stepped care," in which physicians and patients must first try more established and less costly agents. N-of-1 clinical trials are multiple crossover trials in a single patient. In this cost-minimization analysis, we show that offering patients with rheumatoid arthritis the opportunity to participate in an n-of-1 trial comparing methotrexate with etanercept could save costs relative to open access while preserving clinical freedom relative to mandatory stepped care. In the primary model, the n-of-1 trial option was 15% more expensive than stepped care but 47% cheaper than open access to etanercept. More research is needed on the acceptability, safety, and generalizability of this promising approach.

An economic model of adverse events and costs for oral anticoagulants used for atrial fibrillation.

OBJECTIVE: To construct a semi-Markov model to compare health outcomes and medical costs associated with warfarin and a second anticoagulant over 1- and 5-year periods. DESIGN: We posited a hypothetical cohort of 10,000 identical 70-year-old patients with atrial fibrillation. We posited 20 scenarios for events that included four possibilities for ischemic strokes (mild, moderate, severe, death) and 16 possibilities for hemorrhages. The model allowed for four levels of International Normalized Ratio. Event rates were based on outcomes in clinical trials and observational studies. Costs were estimated from the perspective of the third-party payer. RESULTS: The greatest cost-generating events were virtually the same for the two drugs and included severe stroke ($1,758,548 for 1 year for both drugs), moderate stroke ($380,355 for 1 year for both drugs), and severe lower gastrointestinal (GI) hemorrhage ($193,804 for 1 year for warfarin and $193,474 for second drug). The least costly events for both drugs were mild intracranial or intracerebral hemorrhage ($7584 for warfarin and $4314 for second drug) and fatal upper GI hemorrhage ($16,781 and $16,752). Total costs for adverse events over 5 years were similar: $18,330,662 for warfarin and $17,102,847 for the second drug. Fatalities for 5 years were 123 for warfarin and 101 for the non-warfarin drug. Varying assumptions for nursing home care and numbers of ischemic strokes and hemorrhages generated the widest variation in costs. LIMITATIONS: We did not account for out-of-pocket expenses, 'pain and suffering' costs, or variation across practice settings. CONCLUSIONS: There was substantial variation in numbers and costs of adverse events across 20 scenarios, and for fatalities between the two drugs, but variation in costs between the two drugs was modest.

Mandating coverage of biologic therapies for rheumatic disease: where evidence and politics meet.

In this issue of Arthritis Care & Research, we inaugurate an occasional series of commentaries entitled Policy Matters. In all of clinical research, our goal is to improve patient outcomes. Usually, that means focusing on the medical, demographic, and socioeconomic factors at the level of individuals with rheumatic diseases; sometimes, our scope of inquiry expands to encompass the impact of the communities in which they live. However, increasingly, the welfare of persons with rheumatic conditions is also affected by health policies through such diverse mechanisms as reimbursement decisions for specific treatments, insurance coverage, manpower, and NIH budgets (the foregoing list is hardly exhaustive).Recently, a piece of legislation was introduced in California (SB913) that has the potential to alter the availability of biologic response modifying agents (BRMs) by mandating that health plans that provide coverage for one such agent include all on their formularies (a revised version would preclude a trial of another disease-modifying antirheumatic drug before use of a BRM). In this state, the California Health Benefits Review Program (CHBRP) provides evidence reviews of the medical effectiveness, cost, and public health impact of proposed health insurance mandates for the legislature. The analysts from the University of California who conducted the medical effectiveness review of SB913 for CHBRP provide a legislative history of the proposed law in this article. We hope that the readership of Arthritis Care & Research find this article informative as an exemplar of the policies that could dramatically alter the welfare of our patients.