Risk of stroke/systemic embolism,major bleeding and associated costs in non-valvular atrial fibrillation patients who initiated apixaban,dabigatran or rivaroxaban compared with warfarin in the United States Medicare population

Objective: To compare the risk and cost of stroke/systemic embolism (SE) and major bleeding between each direct oral anticoagulant (DOAC) and warfarin among non-valvular atrial fibrillation (NVAF) patients.

Methods: Patients (≥65 years) initiating warfarin or DOACs (apixaban, rivaroxaban, and dabigatran) were selected from the Medicare database from 1 January 2013 to 31 December 2014. Patients initiating each DOAC were matched 1:1 to warfarin patients using propensity score matching to balance demographics and clinical characteristics. Cox proportional hazards models were used to estimate the risks of stroke/SE and major bleeding of each DOAC vs. warfarin. Two-part models were used to compare the stroke/SE- and major-bleeding-related medical costs between matched cohorts.

Results: Of the 186,132 eligible patients, 20,803 apixaban–warfarin pairs, 52,476 rivaroxaban–warfarin pairs, and 16,731 dabigatran–warfarin pairs were matched. Apixaban (hazard ratio [HR]?=?0.40; 95% confidence interval [CI] 0.31, 0.53) and rivaroxaban (HR?=?0.72; 95% CI 0.63, 0.83) were significantly associated with lower risk of stroke/SE compared to warfarin. Apixaban (HR?=?0.51; 95% CI 0.44, 0.58) and dabigatran (HR?=?0.79; 95% CI 0.69, 0.91) were significantly associated with lower risk of major bleeding; rivaroxaban (HR?=?1.17; 95% CI 1.10, 1.26) was significantly associated with higher risk of major bleeding compared to warfarin. Compared to warfarin, apixaban ($63 vs. $131) and rivaroxaban ($93 vs. $139) had significantly lower stroke/SE-related medical costs; apixaban ($292 vs. $529) and dabigatran ($369 vs. $450) had significantly lower major bleeding-related medical costs.

Conclusions: Among the DOACs in the study, only apixaban is associated with a significantly lower risk of stroke/SE and major bleeding and lower related medical costs compared to warfarin.     

Continuation with apixaban treatment is associated with lower risk for hospitalization and medical costs among elderly patients

Objective: To compare the risk of hospitalization and costs associated with major bleeding (MB) or stroke/systemic embolism (SE) among elderly patients with nonvalvular atrial fibrillation (NVAF) who initiated apixaban then switched to another oral anticoagulant (OAC) vs. those who continued with apixaban treatment.

Methods: NVAF patients (≥65?years) initiating apixaban were identified from the Humana database (1 January 2013–30 September 2017) and grouped into switcher and continuer cohorts. For switchers, the earliest switch from apixaban to another OAC was defined as the index event/date. A random date during apixaban treatment was selected as the index date for continuers. Patients were followed from index date to health plan disenrollment or 31 December 2017, whichever was earlier. Multivariable regression analyses were used to examine the association of switchers vs. continuers with risk of MB-related or stroke/SE-related hospitalization and healthcare costs during follow-up.

Results: Of 7858 elderly NVAF patients included in the study, 14% (N?=?1110; mean age: 78?years) were switchers; 86% (N?=?6748; mean age: 79?years) were continuers. Apixaban switchers vs. continuers had significantly greater risk of MB-related hospitalization (hazard ratio [HR]: 2.00; 95% CI: 1.52–2.64; p?<?.001) during follow-up; risk of stroke/SE hospitalization did not differ significantly (HR: 1.36, 95% CI: 0.89–2.06, p?=?.154). MB- and stroke/SE-related medical costs were higher for switchers vs. continuers, although total all-cause healthcare costs were similar.

Conclusion: Elderly patients with NVAF in the US who continued with apixaban treatment had a lower risk of MB-related hospitalization and lower MB- and stroke/SE-related medical costs compared to patients who switched to another OAC.     

Comparison of effectiveness and safety of treatment with apixaban vs. other oral anticoagulants among elderly nonvalvular atrial fibrillation patients

Objective: To compare the risk of stroke/systemic embolism (S/SE) and major bleeding (MB) of elderly (≥65 years of age) nonvalvular atrial fibrillation (NVAF) patients initiating apixaban vs. rivaroxaban, dabigatran, or warfarin.

Methods: NVAF patients with Medicare Advantage coverage in the US initiating oral anticoagulants (OACs, index event) were identified from the Humana database (1 January 2013–30 September 2015) and grouped into cohorts depending on OAC initiated. Propensity score matching (PSM), 1:1, was conducted among patients treated with apixaban vs. each other OAC, separately. Rates of S/SE and MB were evaluated in the follow-up. Cox regressions were used to compare the risk of S/SE and MB between apixaban and each of the other OACs during the follow-up.

Results: The matched pairs of apixaban vs. rivaroxaban (n?=?13,620), apixaban vs. dabigatran (n?=?4654), and apixaban vs. warfarin (n?=?14,214) were well balanced for key patient characteristics. Adjusted risks for S/SE (hazard ratio [HR] vs. rivaroxaban: 0.72, p?=?.003; vs. warfarin: 0.65, p?p?p?p?=?.27) and MB (HR: 0.82, p?=?.23) of NVAF patients treated with apixaban vs. dabigatran trended to be lower, but did not reach statistical significance.

Conclusions: In the real-world setting after controlling for differences in patient characteristics, apixaban is associated with significantly lower risk of S/SE and MB than rivaroxaban and warfarin, and a trend towards better outcomes vs. dabigatran among elderly NVAF patients in the US.     

Warfarin therapy in Chinese patients with atrial fibrillation treated with percutaneous coronary intervention: a 5 year follow-up retrospective cohort study

Objective: To evaluate warfarin use in Chinese patients with atrial fibrillation (AF) undergoing percutaneous coronary intervention (PCI) by investigating the stroke and major adverse cardiac and cerebral events (MACCEs) and bleeding events.

Methods: Retrospective cohort study of the 5?year follow-up of 1134 patients with AF who underwent PCI. The patients were grouped according to whether they received warfarin or not. Baseline characteristics and the occurrence of MACCEs and bleeding events were compared between the two groups using the CHA2DS2-VASc and HAS-BLED scoring. Cox regression analysis was used to identify factors related to the occurrence of MACCEs and bleeding.

Results: Overall MACCE (p?=?.008) and mortality (p?=?.004) rates were significantly lower in the warfarin group compared with the non-warfarin group. Major bleeding, minor bleeding and overall bleeding were comparable in the two groups. Recurrent myocardial infarction (HR?=?10.129, 95% CI?=?4.737–21.655; p?<?.001) and a baseline CHA2DS2-VASc score >4 (HR?=?2.035, 95% CI?=?1.121–3.692; p?=?.019) were independent predictors of MACCEs in the warfarin group. A baseline HAS-BLED score ≥3 (HR?=?5.498, 95% CI?=?3.773–8.013; p?<?.001) and previous bleeding (HR?=?3.058, 95% CI?=?1.319–7.088; p?=?.009) were independent predictors of bleeding.

Conclusions: Warfarin reduces the incidence of MACCEs but does not increase bleeding events in Chinese patients with AF who underwent PCI. For patients taking warfarin, recurrent myocardial infarction and a baseline CHA2DS2-VASc score >4 were related to MACCE occurrence.     

Warfarin time in therapeutic range and its impact on healthcare resource utilization and costs among patients with nonvalvular atrial fibrillation

Background:

Warfarin is efficacious for reducing stroke risk among patients with nonvalvular atrial fibrillation (NVAF). However, the efficacy and safety of warfarin are influenced by its time in therapeutic range (TTR).

Objective:

To assess differences in healthcare resource utilization and costs among NVAF patients with low (<60%) and high (≥60%) warfarin TTRs in an integrated delivery network (IDN) setting.

Methods:

Patients with NVAF were identified from an electronic medical record database. Patients were required to have ≥6 international normalized prothrombin time ratio (INR) tests. NVAF patients were grouped into two cohorts: those with warfarin TTR <60% (low TTR) and those with warfarin TTR ≥60% (high TTR). Healthcare resource utilization and costs were evaluated during a 12 month follow-up period. Multivariable regressions were used to assess the impact of different warfarin TTRs on healthcare costs.

Results:

Among the study population, greater than half (54%, n?=?1595) had a low TTR, and 46% (n?=?1356) had a high TTR. Total all-cause healthcare resource utilization was higher among patients in the low TTR cohort vs. the high TTR cohort (number of encounters: 70.2 vs. 56.1, p?<?0.001). After adjusting for patient characteristics, total all-cause healthcare costs and stroke-related healthcare costs were $2398 (p?<?0.001) and $687 (p?=?0.02) higher, respectively, for patients in the low TTR cohort vs. the high TTR cohort.

Limitations:

In this retrospective study, we were only able to evaluate the association and not the causality between healthcare resource utilization and costs with the different warfarin TTRs.

Conclusion:

Many warfarin-treated NVAF patients have a low warfarin TTR. NVAF patients with low vs. patients with high warfarin TTR used healthcare resources to a greater extent, which was reflected in higher healthcare costs.     

Adverse clinical events in Japanese atrial fibrillation patients with and without coronary artery disease—findings from the SAKURA AF Registry

Abstract

Background: Although atrial fibrillation (AF) and coronary artery disease (CAD) are increasing in prevalence in Japan, real-world data regarding clinical outcomes in Japanese AF patients with CAD are limited.

Methods: The SAKURA AF Registry is a prospective multi-center registry created to investigate outcomes of oral anticoagulant (OAC) use in Japanese AF patients. A study was conducted involving 3237 enrollees from 63 Tokyo-area institutions who were followed up for a median of 39.3?months. Clinical adverse events were compared between the patients accompanied with (n?=?312) and without CAD (n?=?2925).

Results: The incidence of cardiovascular events and all-cause mortality rates were significantly higher among patients with CAD than among those without CAD (5.98 vs 2.52 events per 100 patient-years, respectively, p?<?0.001; 3.27 vs 1.94 deaths per 100 patient-years, respectively, p?=?0.012), but there was no difference in strokes/transient ischemic attacks or systemic embolisms (1.70 vs 1.34). After a multivariate adjustment, CAD remained a risk factor for cardiovascular events (hazard ratio [HR]?=?1.57, 95% confidence interval [CI]?=?1.08–2.25, p?=?0.018). Among CAD patients, the propensity score-adjusted risk for major bleeding was significantly decreased among direct oral anticoagulant (DOAC) users in comparison to that among warfarin users (HR?=?0.29, 95% CI?=?0.07–0.94, p?=?0.04), but other adverse clinical events did not differ significantly between these two groups.

Conclusions: CAD did not appear to be a major determinant of strokes/TIAs, major bleeding, or all-cause mortality, but appeared to increase the risk of cardiovascular events in Japanese AF patients. The risk of major bleeding in CAD patients appeared to decrease when a DOAC rather than warfarin was administered. The data suggested that patients with AF and concomitant CAD require careful management and follow-up to reduce cardiovascular risks, and DOACs may be a better choice over warfarin when considering the risk of major bleeding.     

Healthcare costs among adults with type 2 diabetes initiating saxagliptin or linagliptin: a US-based claims analysis

Objective: To compare healthcare costs of adults with type 2 diabetes (T2D) after initiation of saxagliptin or linagliptin, two antidiabetic medications in the dipeptidyl peptidase-4 inhibitor medication class.

Methods: Patients with T2D who were at least 18 years old and initiated saxagliptin or linagliptin (index date) between 1 June 2011 and 30 June 2014 were identified in the MarketScan Commercial and Medicare Supplemental Databases. All-cause healthcare costs and diabetes-related costs (T2D diagnosis on a medical claim and/or an antidiabetic medication claim) were measured in the 1 year follow-up period. Saxagliptin and linagliptin initiators were matched using propensity score methods. Cost ratios (CRs) and predicted costs were estimated from generalized linear models and recycled predictions.

Results: There were 34,560 saxagliptin initiators and 18,175 linagliptin initiators identified (mean ages 57 and 59; 55% and 56% male, respectively). Before matching, saxagliptin initiators had significantly lower all-cause total healthcare costs than linagliptin initiators (mean?=?$15,335 [SD $28,923] vs. mean =?$20,069 [SD $48,541], p?p?n?=?16,069 per cohort), saxagliptin initiators had lower all-cause follow-up costs than linagliptin initiators (CR?=?0.953, 95% CI?=?0.932–0.974, p?p?=?0.017; predicted costs?=?$3989 vs. $4159).

Conclusions: Adult patients with T2D initiating treatment with saxagliptin had lower total all-cause healthcare costs and diabetes-related medical costs over 1 year compared with patients initiating treatment with linagliptin.     

Risk of major bleeding in patients with non-valvular atrial fibrillation treated with oral anticoagulants: a systematic review of real-world observational studies

Objective: To conduct a systematic review of real-world (RWD) studies comparing the risk of major bleeding (MB) among patients with non-valvular atrial fibrillation (NVAF) on direct oral anticoagulants (DOACs) or warfarin.

Methods: MEDLINE, Embase, NHS-EED, and EconLit were searched for RWD studies published between January 2003 and November 2016 comparing MB risk among DOACs and warfarin. Proceedings of clinical conferences from 2012 to 2016 were reviewed.

Results: A total of 4218 citations were identified, 26 of which met eligibility criteria. Most studies were retrospective analyses of administrative claims databases and patient registries (n?=?23 of 26); about half were based in the United States (n?=?15). Apixaban showed a significantly lower risk of MB versus warfarin in all eight included studies. MB risk was either significantly lower (n?=?9 of 16) or not significantly different (n?=?7 of 16) between dabigatran and warfarin; there was no significant difference between rivaroxaban and warfarin in all seven included studies. The risk was significantly lower with apixaban versus rivaroxaban (n?=?7 of 7) but not significantly different from dabigatran (n?=?6 of 7). MB risk was significantly lower (n?=?3 of 4) or not significantly different (n?=?1 of 4) with dabigatran versus rivaroxaban. No evidence was identified for edoxaban.

Conclusion: DOACs were associated with similar or lower risks of MB versus warfarin. A lower MB risk was consistently observed for apixaban, but less consistently for dabigatran; MB risk was similar between rivaroxaban and warfarin. Among DOACs, the risk of MB with apixaban was consistently lower than with rivaroxaban, but similar to dabigatran.     

Treatment patterns and real-world effectiveness of warfarin in nonvalvular atrial fibrillation within a managed care system

ABSTRACT

Objective: To examine warfarin utilization and clinical effectiveness among patients with nonvalvular atrial fibrillation within usual clinical care in a managed care system.

Research design and methods: A retrospective analysis of health care claims for an approximately four million member managed care organization was performed. Health plan members with a diagnosis of nonvalvular atrial fibrillation in calendar year 2000 were identified and stratified into two cohorts: Warfarin Therapy (newly initiating warfarin) or Warfarin Candidates (eligible for warfarin therapy according to the ACC/AHA/ESC Guidelines for the Management of Patients with Atrial Fibrillation, but did not receive warfarin).

Measurements: The occurrence of thromboembolism, ischemic stroke, and hemorrhage during a maximum 720‐day follow-up were compared between cohorts, adjusting for age, gender, and other risk factors, using Cox regression.

Results: Among 12?539 subjects (mean age 78.0 ± 8.8 years) with nonvalvular atrial fibrillation, 4895 (39.0%) initiated Warfarin Therapy and 7644 (61.0%) were Warfarin Candidates. Event occurrences among Warfarin Therapy vs. Warfarin Candidates were: ischemic stroke, 3.7% vs. 4.5%; any thromboembolism, 7.8% vs. 10.8%; and hemorrhage, 4.4% vs. 4.9%, respectively. Warfarin therapy was not associated with an increased risk for hemorrhage (hazard ratio [HR] = 0.97, 95% confidence interval [CI] = 0.82–1.15), while risks for ischemic stroke and any thromboembolism were significantly reduced, by 22% (HR = 0.78, 95% CI = 0.65–0.93) and 34% (HR = 0.66, 95% CI = 0.59–0.75), respectively.

Conclusions: Within usual clinical care for the managed care population examined, warfarin remains underused despite current guidelines recommending its use in nearly all patients with nonvalvular atrial fibrillation. Although utilization of anticoagulation clinics and INR values attained were unknown in this study, the observed risk reductions for ischemic stroke and thromboembolism were lower than those achieved in clinical trials, while no increased risk for hemorrhage was observed. These findings suggest that warfarin is used conservatively, and dosed cautiously, diminishing the full potential benefit of anticoagulant therapy in patients with nonvalvular atrial fibrillation.     

An early evaluation of bleeding-related hospital readmissions among hospitalized patients with nonvalvular atrial fibrillation treated with direct oral anticoagulants

Objective:

Clinical trials have demonstrated that direct oral anticoagulants (DOACs) are efficacious in reducing stroke risk among patients with nonvalvular atrial fibrillation (NVAF) with differences in the reduction of bleeding risks vs. warfarin. The objective of this study was to assess bleeding-related hospital readmissions among hospitalized NVAF patients treated with dabigatran, rivaroxaban, and apixaban in the US.

Research design and methods:

Patients (≥18 years) with a discharge diagnosis of NVAF who received apixaban, dabigatran, or rivaroxaban during hospitalization were identified from the Premier Hospital database (1 January 2012–31 March 2014) and the Cerner Health Facts hospital database (1 January 2012–31 August 2014). Patients identified from each database were analyzed separately and grouped into three cohorts depending on which DOAC was received. Patient characteristics, hospital resource use and costs, and frequency of readmissions within 1 month were evaluated.

Results:

Among study populations identified from the Premier database (N?=?74,730) and the Cerner database (N?=?14,201), patients who received apixaban were older, had greater comorbidity, and had higher stroke and bleeding risks. After controlling for patient characteristics, including comorbidity and stroke and bleeding risks, compared with patients who received apixaban during their index hospitalizations, the odds of bleeding-related hospital readmissions were significantly greater by 1.4-fold (p?<?0.01) for patients who received rivaroxaban and 1.2-fold (p?=?0.16) numerically greater for patients who received dabigatran among patients identified from the Premier Hospital database. Among patients in the Cerner Health Facts hospital database, bleeding-related hospital readmissions were significantly greater by 1.6-fold (p?=?0.04) for patients who received rivaroxaban and 1.3-fold (p?=?0.30) numerically greater for patients who received dabigatran compared to patients who received apixaban.

Limitations:

No causal relationship between treatment and outcomes can be concluded.

Conclusions:

NVAF patients using different DOACs had different characteristics, including stroke and bleeding risks. Use of rivaroxaban, compared to apixaban was associated with significantly greater risk of bleeding-related readmissions across two database claims analyses.     

Safety and efficacy of non-vitamin K oral anticoagulants in non-valvular atrial fibrillation: a Bayesian meta-analysis approach

Introduction: Choosing between different non-vitamin K antagonist oral anticoagulants (NOACs) in non-valvular atrial fibrillation (NVAF) is difficult due to the absence of head to head comparative studies. We performed a Bayesian meta-analysis to explore similarities and differences between different NOACs and to rank treatments overall for safety and efficacy outcomes.

Areas covered: Through a systematic literature search we identified randomized controlled Phase III trials of dabigatran, rivaroxaban, apixaban, and edoxaban versus adjusted-dose warfarin in patients with NVAF.

Expert opinion: Warfarin ranked worst for all-cause mortality and intracranial bleedings and had a nil probability of ranking first for any outcome. The risk of major bleeding versus warfarin was lower with apixaban, dabigatran 110 mg, and both doses of edoxaban. All agents reduced the risk of intracranial bleeding versus warfarin. Edoxaban 30 mg was the best among the treatments being compared for major and gastrointestinal bleeding. Dabigatran 150 mg was the best for stroke and systemic embolism. This study suggests that NOACs are generally preferable to warfarin in patients with NVAF. However, safety and efficacy differences do exist among NOACs, which might drive their use in specific subsets of AF patients, allowing prescribers to tailor treatment to distinct patient profiles.     

Efficacy and safety of venous thromboembolism prophylaxis with fondaparinux or low molecular weight heparin in a large cohort of consecutive patients undergoing major orthopaedic surgery – findings from the ORTHO-TEP registry

AIMS

In large randomized trials, thromboprophylaxis with fondaparinux in major orthopaedic surgery (MOS) has been shown to be superior to low molecular weight heparin (LMWH) prophylaxis with comparable safety. However, patients treated under trial conditions are different from unselected patients and efficacy and safety outcomes may be different in unselected patients in daily practice. We performed a retrospective cohort study to compare the efficacy and safety of venous thromboembolism (VTE) prophylaxis with fondaparinux or LMWH in 3896 consecutive patients undergoing major orthopaedic surgery at our centre.

METHODS

All patients undergoing MOS between January 2006 and December 2009 were retrospectively analyzed using patient charts, hospital admission and discharge database, quality management database, transfusion unit database and VTE event documentation. VTE standard prophylaxis at our institution was LMWH (3000–6000 aXa units once daily) from January 2006 to December 2007 or fondaparinux 2.5 mg from January 2008 to December 2009. In these two large cohorts of unselected consecutive patients, in-hospital incidences of VTE, surgical complications, severe bleeding and death were evaluated.

RESULTS

Symptomatic VTE was found in 4.1% of patients in the LMWH group (62/1495 patients; 95% CI 0.032, 0.052) compared with 5.6% of patients receiving fondaparinux (112/1994 patients, 95% CI 0.047, 0.067; P= 0.047). Distal deep vein thrombosis (DVT) was significantly more frequent in the fondaparinux group (3.9%, 95% CI 0.031, 0.048; vs. 2.5%; 95% CI 0.018, 0.034; P= 0.021). No significant differences in the rates of major VTE or death were found. Rates of severe bleeding, transfusion of RBC concentrates, plasma and platelet concentrates were comparable between both treatment groups. However, patients receiving fondaparinux had significantly lower rates of surgical revisions (1.6%, 95% CI 0.011, 0.022 vs. 3.7%, 95% CI 0.028, 0.047; P < 0.001). Multivariate analysis revealed previous VTE (HR 18.2, 95% CI 11.6, 28.5; P < 0.001) and female gender (HR 1.9, 95% CI 1.3, 2.7; P < 0.001), but not fondaparinux prophylaxis (HR1.3, 95% CI 0.9, 1.7; P= 0.184) to be associated with significantly increased VTE risk.

DISCUSSION

Thromboprophylaxis with fondaparinux is less effective to prevent distal VTE than LMWH in unselected patients undergoing MOS, but is equally effective with regard to rates of major VTE and death. However, differences in efficacy of LMWH or fondaparinux are of little relevance compared with a history of VTE or female gender, which were found to be the main VTE risk factors in MOS. The safety profile of fondaparinux was comparable with LMWH with regard to rates of severe bleeding complications, but patients receiving fondaparinux had significantly less surgical complications requiring surgical revisions. Both our efficacy and safety findings differ from data derived from large phase III trials testing fondaparinux against LMWH in MOS, where overall rates of symptomatic VTE were lower and the safety profile of fondaparinux was different.

CONCLUSION

We conclude that the strict patient selection and surveillance in phase-III trials results in lower VTE and bleeding event rates compared with unselected routine patients. Consequently, the efficacy and safety profile of thromboprophylaxis regimens needs to be confirmed in large registries or phase IV trials of unselected patients.     

Safety and effectiveness of thromboprophylaxis use in hospitalized elderly medical patients at a Saudi tertiary care center

IntroductionAppropriate prescribing of thromboprophylaxis according to guidelines’ recommendations can heighten over- or underutilization risk. The study intended to evaluate the safety and effectiveness of appropriate/inappropriate thromboprophylaxis use among hospitalized elderly medical patients.MethodsA retrospective observational cohort study was conducted, including patients who were ≥60 years old, hospitalized for an acute medical illness that required hospitalization in a medical ward for >48 h, and received thromboprophylaxis. Against the American College of Chest Physicians guidelines, the thromboprophylaxis use appropriateness was assessed.ResultsA total of 370 patients met the inclusion criteria, in 71.9% of whom thromboprophylaxis use was appropriate. The mean age of the included patients was 75 years (±9.1), and 72.4% of them were at high risk of venous thromboembolism (VTE), and almost all these patients received appropriate thromboprophylaxis. The occurrence of bleeding was significantly higher in the appropriate use group during hospitalization than the inappropriate use group (11.7% vs. 2.9%, p = 0.009); the majority of these bleeding events were classified as major. There were no differences in VTE events during hospitalization or 90 days all-cause mortality between the two groups.ConclusionThe study demonstrates high prescribers’ compliance with recommendations in high-risk patients. In patients at low risk for VTE, the overutilization of thromboprophylaxis did not increase their bleeding risk. This study suggests that the benefits of thromboprophylaxis in elderly patients, regardless of their VTE risk, may outweigh the risk of bleeding.     

Treatment patterns,overall survival,healthcare resource use and costs in elderly Medicare beneficiaries with chronic myeloid leukemia using second-generation tyrosine kinase inhibitors as second-line therapy

Objective Though the median age at diagnosis is 64 years, few studies focus on elderly (≥65 years) patients with chronic myeloid leukemia (CML). This study examines healthcare outcomes among elderly Medicare beneficiaries with CML who started nilotinib or dasatinib after imatinib.

Research design and methods Patients were identified in the Medicare Research Identifiable Files (2006–2012) and had continuous Medicare Parts A, B, and D coverage.

Main outcome measures Treatment patterns, overall survival (OS), monthly healthcare resource utilization and medical costs were measured from the second-line tyrosine kinase inhibitor (TKI) initiation (index date) to end of Medicare coverage.

Results Despite similar adherence, dasatinib patients (N?=?379) were more likely to start on the recommended dose (74% vs. 53%; p?<?0.001), and to have dose reductions (21% vs. 11%, adjusted hazard ratio [HR]?=?1.94; p?=?0.002) or dose increases (9% vs. 7%; adjusted HR?=?1.81; p?=?0.048) than nilotinib patients (N?=?280). Fewer nilotinib patients discontinued (59% vs. 67%; adjusted HR?=?0.80; p?=?0.026) or switched to another TKI (21% vs. 29%; adjusted HR?=?0.72; p?=?0.044) than dasatinib patients. Nilotinib patients had longer median OS (>4.9 years vs. 4.0 years; p?=?0.032) and 37% lower mortality risk than dasatinib patients (adjusted HR?=?0.63; p?=?0.008). Nilotinib patients had 23% fewer inpatient admissions, 30% fewer emergency room visits, 13% fewer outpatient visits (all p?<?0.05), and lower monthly medical costs (by $513, p?=?0.024) than dasatinib patients.

Limitations Lack of clinical assessment (disease phase and response to first-line therapy) and retrospective nature of study (unobservable potential confounding factors, non-randomized treatment choice).

Conclusions In the current study of elderly CML patients, initiation of second-line TKIs frequently occurs at doses lower than the recommended starting doses and, despite this, many patients require dose adjustments. Here, nilotinib patients required fewer dose adjustments than dasatinib patients. Further research focusing on elderly CML patients is warranted in order to help define future best clinical practices.     

Cost implications of IV versus oral anti-angiogenesis therapies in patients with advanced renal cell carcinoma: retrospective claims database analysis*

ABSTRACT

Objective: Angiogenesis inhibitors (AI) are promising novel treatments for patients with renal cell carcinoma (RCC). However, IV therapy may impose infection risk from IV catheters, and will include increased costs due to administration and transportation costs. This study evaluated the incremental costs associated with IV administration of selected AI therapies (bevacizumab off-label) compared to oral therapies (sunitinib or sorafenib) for the treatment of RCC.

Methods: Patients with ≥2 RCC claims (ICD-9: 189.0, 198.0) were identified from a US commercial health insurance claims database from 1/2004 to 12/2007. Patients receiving bevacizumab (n?=?109) were matched 1:1 to patients receiving sorafenib or sunitinib, and observed from their first AI therapy claim until the last treatment date. AI, inpatient, outpatient and pharmacy costs were calculated on a per-patient per-month (PPPM) basis over the treatment period. Costs were compared between the IV AI group and each separate oral AI group using multivariate Tobit regressions for each category separately, adjusting for demographic and baseline clinical characteristics. This study assessed costs of treatment and did not evaluate the cost-effectiveness of AIs.

Results: Mean total medical costs were $13?351, $6998, and $8213 PPPM for bevacizumab, sorafenib, and sunitinib, respectively (p?<0.05 for equality). Adjusted incremental total cost for the bevacizumab group was $4951 PPPM compared to sorafenib and $4610 PPPM compared to sunitinib (both p?<?0.05). Bevacizumab patients incurred incremental PPPM outpatient services cost compared to sorafenib and sunitinib of $2772 and $2548, respectively (both p?<?0.05).

Conclusions: Assuming median progression-free survival of 8.5 months as shown for bevacizumab (Bukowski, et al., J Clin Oncol 2007), the incremental costs would be estimated at $39?188–42?080 per patient compared to those treated with sunitinib or sorafenib. Assuming similar efficacies, oral AI therapies may result in cost savings to patients and healthcare payers over IV therapies.