Impact of 5-HT3 receptor antagonists on chemotherapy-induced nausea and vomiting: a retrospective cohort study

BACKGROUND: 1(st) generation 5-hydroxytryptamine receptor antagonists (5-HT(3) RAs), and palonosetron, a 2(nd) generation 5-HT(3) RA, are indicated for the prevention of chemotherapy (CT)-induced nausea and vomiting (CINV) associated with moderately (MEC) and highly emetogenic CT agents (HEC). This study explores the impact of step therapy policies requiring use of an older 5-HT(3) RA before palonosetron on risk of CINV associated with hospital or emergency department (ED) admissions. METHODS: Patients who received cyclophosphamide post breast cancer (BC) surgery or who were diagnosed with lung cancer on carboplatin (LC-carboplatin) or cisplatin (LC-cisplatin) were selected from PharMetrics’ (IMS LifeLink) claims dataset (2005-2008). Patients were followed for 6 months from initial CT administration for CINV events identified through ICD-9-CM codes. Patients were grouped into those initiated with older, generic 5-HT(3) RAs (ondansetron, granisetron, and dolasetron) and those initiated and maintained on palonosetron throughout study follow-up. CINV events and CINV days were analyzed using multivariate regressions controlling for demographic and clinical variables. RESULTS: Eligible patients numbered 3,606 in BC, 4,497 in LC-carboplatin and 1,154 in LC-cisplatin cohorts, with 52%, 40%, and 34% in the palonosetron group, respectively. There was no significant difference between the two 5-HT(3) RA groups in age or Charlson Comorbidity Index among the two MEC cohorts (BC and LC-carboplatin). Among the LC-cisplatin cohort, palonosetron users were older with more males than the older 5-HT(3) RA group (age: 60.1 vs. 61.3; males, 66.9% vs. 56.9%). Compared to the older 5-HT(3) RAs, the palonosetron groups incurred 22%-51% fewer 5-HT(3) RA pharmacy claims, had fewer patients with CINV events (3.5% vs. 5.5% in BC, 9.5% vs. 12.8% in LC-carboplatin, 16.4% vs. 21.7% in LC-cisplatin), and had lower risk for CINV events (odds ratios 0.62, 0.71, or 0.71, respectively; p < 0.05). The BC and LC-carboplatin palonosetron groups experienced 50% and 30% fewer CINV days than the generic 5-HT(3) RA group (p < 0.05). CONCLUSIONS: Patients with breast or lung cancer initiated and maintained on palonosetron were at significantly lower risk for potentially costly CINV versus those on older 5-HT(3) RAs. Further studies on impact of step therapy policy are warranted in order to minimize the clinical and economic burden of CINV

Oral anticoagulant decreases stroke recurrence in patients with atrial fibrillation detected after stroke

Background: Atrial fibrillation detected after stroke (AFDAS) has a lower risk of ischemic stroke recurrence than known atrial fibrillation (KAF). While the benefit of oral anticoagulants (OAC) for preventing ischemic stroke recurrence in KAF is well established, their role in patients with AFDAS is more controversial. This study aimed to evaluate the association between OAC use and the risk of recurrent ischemic stroke in patients with AFDAS in a real-world setting. Methods: This nationwide retrospective cohort study was conducted using the Taiwan National Health Insurance Research Database. Patients hospitalized with a first-ever ischemic stroke and AFDAS confirmed within 30 days after hospitalization were assigned to OAC and non-OAC cohorts. Inverse probability of treatment weighting was applied to balance the baseline characteristics of the cohorts. The primary outcome was ischemic stroke recurrence. Secondary outcomes were intracranial hemorrhage (ICH), death, and the composite outcome of “ischemic stroke recurrence, ICH, or death.” Multivariate Cox proportional hazard models were used to estimate adjusted hazard ratios (aHR) and 95% confidence intervals (CI). Results: A total of 4,508 hospitalized patients with stroke and AFDAS were identified. Based on OAC use, 2,856 and 1,652 patients were assigned to the OAC and non-OAC groups, respectively. During the follow-up period (median duration, 2.76 years), the OAC cohort exhibited a lower risk of ischemic stroke recurrence (aHR, 0.84; 95% CI, 0.70–0.99), death (aHR, 0.65; 95% CI, 0.58–0.73), and composite outcome (aHR, 0.70; 95% CI, 0.63–0.78) than did the non-OAC cohort. The risk of ICH (aHR, 0.96; 95% CI, 0.62–1.50) was not significantly different between the two cohorts. Conclusion: OAC use in patients with AFDAS was associated with reduced risk of ischemic stroke recurrence, without an increased risk of ICH. This supports current guidelines recommending OACs for secondary stroke prevention in patients with AF, regardless of the time of diagnosis

Oral anticoagulant decreases stroke recurrence in patients with atrial fibrillation detected after stroke

BackgroundAtrial fibrillation detected after stroke (AFDAS) has a lower risk of ischemic stroke recurrence than known atrial fibrillation (KAF). While the benefit of oral anticoagulants (OAC) for preventing ischemic stroke recurrence in KAF is well established, their role in patients with AFDAS is more controversial. This study aimed to evaluate the association between OAC use and the risk of recurrent ischemic stroke in patients with AFDAS in a real-world setting.MethodsThis nationwide retrospective cohort study was conducted using the Taiwan National Health Insurance Research Database. Patients hospitalized with a first-ever ischemic stroke and AFDAS confirmed within 30 days after hospitalization were assigned to OAC and non-OAC cohorts. Inverse probability of treatment weighting was applied to balance the baseline characteristics of the cohorts. The primary outcome was ischemic stroke recurrence. Secondary outcomes were intracranial hemorrhage (ICH), death, and the composite outcome of “ischemic stroke recurrence, ICH, or death.” Multivariate Cox proportional hazard models were used to estimate adjusted hazard ratios (aHR) and 95% confidence intervals (CI).ResultsA total of 4,508 hospitalized patients with stroke and AFDAS were identified. Based on OAC use, 2,856 and 1,652 patients were assigned to the OAC and non-OAC groups, respectively. During the follow-up period (median duration, 2.76 years), the OAC cohort exhibited a lower risk of ischemic stroke recurrence (aHR, 0.84; 95% CI, 0.70–0.99), death (aHR, 0.65; 95% CI, 0.58–0.73), and composite outcome (aHR, 0.70; 95% CI, 0.63–0.78) than did the non-OAC cohort. The risk of ICH (aHR, 0.96; 95% CI, 0.62–1.50) was not significantly different between the two cohorts.ConclusionOAC use in patients with AFDAS was associated with reduced risk of ischemic stroke recurrence, without an increased risk of ICH. This supports current guidelines recommending OACs for secondary stroke prevention in patients with AF, regardless of the time of diagnosis

Diffusion of healthcare technology: Adoption of fentanyl patch by physicians in Illinois.

Diffusion of healthcare technology: Adoption of fentanyl patch by physicians in Illinois

Impact of 5-Hydroxytryptamine-3 Receptor Antagonist Step Therapy on Severe Chemotherapy-Induced Nausea and Vomiting Events in Patients with Lymphoma

Abstract Abstract 3137 Introduction: Older 5-hydroxytryptamine3 receptor antagonists (5-HT-3 RA), e.g., ondansetron and the more recent palonosetron are indicated for prevention of chemotherapy (CT) induced nausea and vomiting (CINV). Step therapy is a policy that encourages the use of generic 5-HT3 RAs, reserving prophylaxis with palonosetron as second-line therapy as means to containing costs. Objective: To evaluate potential impact of step therapy policy on risk of severe CINV events among patients (pts) with lymphoma who used ondansetron, granisetron, or dolasetron and later switched to palonosetron versus pts who were initiated and maintained on palonosetron throughout multiple CT cycles. Methods: Pts initially diagnosed with lymphoma during 2005–2009 were selected from PharMetrics claims dataset if enrolled for ≥6 months before first lymphoma diagnosis and received cyclophosphamide based CT and 5-HT-3 RA prophylaxis. Pts were followed (FUP) for 6 months from 1st CT date. Based on 5-HT-3 RA used at FUP, pts were grouped into those initiated and maintained on palonosetron throughout versus those initiated with an earlier 5-HT-3 RA and later switched to palonosetron. Outcomes included risk of severe CINV (using ICD-9 codes) associated with hospitalizations or ER admissions, as well as days with severe CINV. Logistic and Poisson regression models were used to compare risk and days with severe CINV, adjusting for cyclophosphamide dose received during the 6-month FUP, age, gender, Charlson Comorbidity Index (CCI), and the year of lymphoma diagnosis. Results: A total of 953 patients who used palonosetron throughout the FUP (palonosetron group) and 113 patients who switched from an older 5-HT-3 RA to palonosetron (switched group) were analyzed. The average (mean±SD) age at lymphoma diagnosis was 60.3±13.8 years, CCI was 0.47±0.97, number of cyclophosphamide treatment days was 5.6±1.93, and cyclophosphamide dose (mg/m2) per CT cycle was 930±676. Palonosetron group was significantly older (60.8 vs. 55.9 years, p=0.0006). There were no significant differences (NS) between the two groups in gender, CCI, or year of lymphoma diagnosis. Palonosetron group had significantly fewer 5-HT-3 RA prescription claims (4.81 vs. 7.72, p&lt;0.0001). There was NS difference between the two groups in cyclophosphamide dose [palonosetron: 937 vs. switched: 871], p&gt;0.05), although palonosetron group had significantly fewer CT treatment days (5.5 vs. 6.3, p=0.0135). Proportion of patients with ≥1 severe CINV events was significantly higher in the switched group (15.9% vs. 6.3%, p=0.0002). Switched group also had significantly more claims and days with severe CINV (2.4 vs. 0.6 in CINV claims, p=0.0001; 0.4 vs. 0.1 in CINV days, p=0.0002). Logistic regression controlling for covariates showed the palonosetron group to experience significantly lower risk of approximately 70% for hospital/ER related CINV than the switched group (Odds Ratio=0.311, p=0.0001), while older age significantly increased such an outcome. Poisson regression with number of days with severe CINV as the outcome variable found that palonosetron group had nearly 75% fewer hospital/ER related CINV days than the switched group (p=0.0024). Conclusion: Patients with lymphoma initiated and maintained on palonosetron throughout the CT cycles were at significantly lower risk and experienced fewer days with severe CINV as compared to those who were initiated on an older 5-HT-3 RA and later on switched to palonosetron. Further studies of the impact of step therapy policy with regard to first 5-HT3-RA therapy in patients with lymphoma are needed in order to assess the related economic and humanistic burden. Disclosures: Hatoum: Eisai: Consultancy, Research Funding. Lin:Eisai: Consultancy. Balu:Eisai: Employment. </jats:sec