François Laliberté

Real-world comparative effectiveness and safety of rivaroxaban and warfarin in nonvalvular atrial fibrillation patients

Abstract Background: Rivaroxaban was shown to be effective in reducing the risk of stroke and systemic embolism in patients with nonvalvular atrial fibrillation (AF) in a randomized controlled trial setting. Objective: To assess real-world safety, effectiveness, and persistence associated with rivaroxaban and warfarin in nonvalvular AF patients. Methods: Healthcare claims from Symphony Health Solutions’ Patient Transactional Datasets from May 2011 to July 2012 were analyzed. Adult patients newly initiated on rivaroxaban or warfarin, with ≥2 AF diagnoses (ICD-9-CM: 427.31) and a CHADS2 score ≥1 during the 180 day baseline period were included. Cohorts were matched 1:4 using propensity score methods. Study outcomes were major bleeding, intracranial hemorrhage (ICH), gastrointestinal (GI) bleeding, composite stroke and systemic embolism, and venous thromboembolism (VTE) events. Cox proportional hazard models were used to compare event and persistence rates. Results: The matched sample included 3654 rivaroxaban and 14,616 warfarin patients. Matching was adequate, with all standardized differences in patient characteristics <10%. No significant differences were observed for bleeding and composite stroke and systemic embolism outcomes, although rivaroxaban users were associated with significantly fewer VTE events (hazard ratio [HR] = 0.36, 95% confidence interval [CI]: 0.24–0.54, p < 0.0001) compared to warfarin users. Rivaroxaban was also associated with a significantly lower risk of treatment non-persistence (HR = 0.66; 95% CI: 0.60–0.72, p < 0.0001). Limitations: Claims data may have contained inaccuracies, and mortality and laboratory data were not available. Confounding may still have been possible even after propensity score matching. Early use pattern of medications may have changed over time. Conclusion: This analysis suggests that rivaroxaban and warfarin do not differ significantly in real-world rates of composite stroke and systemic embolism and major, intracranial, or GI bleeding. Rivaroxaban, however, was associated with significantly fewer VTE events and significantly better treatment persistence compared with warfarin.

Impact of Daily Dosing Frequency on Adherence to Chronic Medications Among Nonvalvular Atrial Fibrillation Patients

IntroductionMultiple daily dosing may be negatively associated with patient medication adherence, but the findings are inconclusive. The objective of this study was to compare adherence rates to once-daily (q.d.) versus twice-daily (b.i.d.) dosing regimen of chronic medications in patients with nonvalvular atrial fibrillation (AF).Patients and MethodsThe authors analyzed the PharMetrics Integrated Claims database from January 1, 2004 to December 31, 2009. Adult patients with continuous insurance coverage, newly initiated on diabetes or hypertension medication, and having at least one AF diagnosis with no valvular heart disease or valve replacement procedures were included. Compliance to q.d. and b.i.d. therapies was calculated in two ways: medication possession ratio (MPR) and proportion of days covered (PDC). Adherence was defined as an MPR or PDC ≥0.8. Multivariate logistic regressions were conducted to compare the probability of adherence between the q.d. and b.i.d. groups adjusting for baseline confounders.ResultsA total of 8,256 q.d. and 2,441 b.i.d. patients were identified. The mean duration of exposure to therapy for q.d. and b.i.d. patients was 447 and 406 days (P < 0.001), respectively. Based on MPR, 75.3% of q.d. and 70.4% of b.i.d. patients were adherent (P < 0.001). For PDC at 12 months, the proportion of adherent patients for the q.d. and b.i.d. groups was 56.5% and 49.6% (P < 0.001), respectively. Adjusted odds ratios (95% CI) of adherence for the q.d. relative to b.i.d. group were 1.26 (1.13, 1.41) based on MPR and 1.23 (1.07, 1.41) based on PDC at 12 months.ConclusionThis study demonstrates that nonvalvular AF patients treated with q.d. dosing regimens for chronic medications were associated with approximately a 26% higher likelihood of adherence compared with subjects on b.i.d. regimens.

Does the route of administration for estrogen hormone therapy impact the risk of venous thromboembolism? Estradiol transdermal system versus oral estrogen-only hormone therapy.

Objective:The aim of this study was to quantify the magnitude of risk reduction for venous thromboembolism events associated with an estradiol transdermal system relative to oral estrogen-only hormone therapy agents. Methods:A claims analysis was conducted using the Thomson Reuters MarketScan database from January 2002 to October 2009. Participants 35 years or older who were newly using an estradiol transdermal system or an oral estrogen-only hormone therapy with two or more dispensings were analyzed. Venous thromboembolism was defined as one or more diagnosis codes for deep vein thrombosis or pulmonary embolism. Cohorts of estradiol transdermal system and oral estrogen-only hormone therapy were matched 1:1 based on both exact factor and propensity score matching, and an incidence rate ratio was used to compare the rates of venous thromboembolism between the matched cohorts. Remaining baseline imbalances from matching were included as covariates in multivariate adjustments. Results:Among the matched estradiol transdermal system and oral estrogen-only hormone therapy users (27,018 women in each group), the mean age of the cohorts was 48.9 years; in each cohort, 6,044 (22.4%) and 1,788 (6.6%) participants had a hysterectomy and an oophorectomy at baseline, respectively. A total of 115 estradiol transdermal system users developed venous thromboembolism, compared with 164 women in the estrogen-only hormone therapy cohort (unadjusted incidence rate ratio, 0.72; 95% CI, 0.57-0.91; P = 0.006). After adjustment for confounding factors, the incidence of venous thromboembolism remained significantly lower for estradiol transdermal system users than for estrogen-only hormone therapy users. Conclusions:This large population-based study suggests that participants receiving an estradiol transdermal system have a significantly lower incidence of venous thromboembolism than do participants receiving oral estrogen-only hormone therapy.

Adherence to non-vitamin-K-antagonist oral anticoagulant medications based on the Pharmacy Quality Alliance measure

Abstract Background: CMS Star Ratings help inform beneficiaries about the performance of health and drug plans. Medication adherence is currently weighted at nearly half of a Part D plan’s Star Ratings. Including the adherence to non-vitamin-K-antagonist oral anticoagulants (NOACs) as a measure in the Star Ratings program may increase a plan’s incentives to improve patient adherence. Objective: To assess the adherence to medication of patients who used the NOACs rivaroxaban, dabigatran, or apixaban in 2014 based on the Pharmacy Quality Alliance (PQA) adherence measure. Methods: Healthcare claims from the Humana database between July 2013 and December 2014 were analyzed. Adult patients with ≥2 dispensings of NOAC agents in 2014, at least 180 days apart, with >60 days of supply, and ≥180 days of continuous enrollment prior to the index NOAC were identified. The PQA measure was calculated as the percentage of patients who had a proportion of days covered (PDC) ≥0.8. Multivariate logistic regression analyses were also conducted adjusting for baseline confounders. Results: A total of 11,095 rivaroxaban, 6548 dabigatran, and 3532 apixaban users were identified. Based on the PQA adherence measure (PDC ≥0.8), a significantly higher proportion of rivaroxaban users (72.7%) was found to be adherent compared to dabigatran (67.2%: p < 0.001) and apixaban (69.5%: p < 0.001) users. Compared to apixaban users, the adjusted likelihood of being adherent was significantly higher for rivaroxaban users (unadjusted OR [95% CI]: 1.17 [1.08–1.27], p < 0.001; adjusted OR [95% CI]: 1.20 (1.10–1.31), p < 0.001) and significantly lower for dabigatran users (unadjusted OR [95% CI]: 0.90 [0.82–0.98], p = 0.019; adjusted OR [95% CI]: 0.85 [0.77–0.93], p < 0.001). Limitations: Limitations of the study are potential inaccuracies in claims data, possible change in patterns over time, and the impossibility of knowing whether all supplied tablets were taken. Conclusion: Using the PQA’s adherence measure, rivaroxaban users were found to have significantly higher adherence compared to apixaban and dabigatran users.

Hospital length of stay: is rivaroxaban associated with shorter inpatient stay compared to warfarin among patients with non-valvular atrial fibrillation?

Abstract Background: Warfarin has been the mainstay treatment for prevention of stroke among patients with non-valvular atrial fibrillation (NVAF). Unlike rivaroxaban, warfarin requires laboratory monitoring to allow the attainment of the prothrombin time (PT) international normalized ratio (INR) goal, thereby potentially prolonging a patient’s hospital length of stay (LOS). Objective: To compare hospital LOS between hospitalized NVAF patients using rivaroxaban versus warfarin in a real-world setting. Methods: A retrospective claims analysis was conducted using the Premier Perspective Comparative Hospital Database from 11/2010 to 9/2012. Adult patients were included in the study if they had a hospitalization for NVAF. Patients using rivaroxaban during hospitalization were matched with up to four warfarin users by propensity score analyses. Patients who were first administered their oral anticoagulants on day 3 or later of their hospital stay were also evaluated. Comparison of hospital LOS was assessed using generalized estimating equations. Results: The characteristics of the matched cohorts were well balanced. Among the matched rivaroxaban and warfarin users (2809 and 11,085 patients, respectively), the mean age of the cohorts was 71 years and 49% of patients were female. The average (median) hospital LOS for rivaroxaban patients was 4.46 (3) days, compared to 5.27 (4) days for the warfarin cohort. The mean difference in hospital LOS of 0.81 days (19.44 hours) was found to be significant at P < 0.001. Patients who were administered rivaroxaban on day 3 of their hospital stay or later also had a significantly lower LOS compared to warfarin users. Limitations: These included inaccuracies or omissions in diagnoses, completeness of baseline characteristics, and a study population that included patients newly initiated on and patients who continued anticoagulant therapy. Conclusion: The study sample of NVAF patients receiving rivaroxaban was associated with a significantly shorter hospital length of stay compared to the sample of patients receiving warfarin.

Direct and indirect cost burden associated with multiple sclerosis relapses: Excess costs of persons with MS and their spouse caregivers

BACKGROUND MS relapses are unpredictable and can be concerning to patients and their caregivers. OBJECTIVE To assess the direct and indirect cost burden associated with relapses of different severities in MS patients and with MS relapse frequency on spouse caregivers. METHODS Using a U.S. insurance claims and employee disability database (1999-2011), we studied adult MS patients (ICD-9-CM: 340.x) and their spouse caregivers. A previously published algorithm to identify relapses was used to stratify: (1) MS patients into cohorts of no, low/moderate, and high severity relapse based on the most severe relapse within one year of follow-up (if any); (2) caregivers into cohorts of no, less, and more frequent relapses based on the overall frequency of relapses of their spouse. Adjusted cost differences and 95% confidence intervals evaluating the yearly incremental costs at 12 months of follow-up (MS patients) and overall (caregivers) associated with relapses are reported. RESULTS Among the 9421 MS patients (N: no relapse=7686; low/moderate severity relapse=1220; high severity relapse=515) identified, both relapse cohorts incurred significantly higher annual incremental direct costs than the no relapse cohort (low/moderate severity=

Cost Burden and Treatment Patterns Associated with Management of Heavy Menstrual Bleeding

8269 [6565-10,115]; high severity=

Pharmacy quality alliance measure: adherence to non-warfarin oral anticoagulant medications

24,180 [20,263-28,482]) and indirect costs (low/moderate severity=

In-hospital risk of venous thromboembolism and bleeding and associated costs for patients undergoing total hip or knee arthroplasty

1429 [759-2147]; high severity=

All-cause and disease-related health care costs associated with recurrent venous thromboembolism

2714 [1468-4035]). More frequent relapses versus no relapse also translated into a significantly greater cost burden for caregivers (direct+indirect=