William H. Olson

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.

A Multicenter, Open-Label, Randomized Comparison of Levofloxacin and Azithromycin Plus Ceftriaxone in Hospitalized Adults with Moderate to Severe Community-Acquired Pneumonia

BACKGROUND Changing etiologic patterns and the growing problem of antimicrobial resistance, particularly an increase in macrolide-resistant pneumococcal bacteremia, are causing physicians to adopt new approaches to the treatment of community-acquired pneumonia (CAP). OBJECTIVE The relative efficacy and tolerability of levofloxacin monotherapy and azithromycin and ceftriaxone combination therapy were assessed in hospitalized adults with moderate to severe CAP. METHODS This Phase IV, multicenter, open-label, randomized trial compared 2 treatment regimens: (1) levofloxacin 500 mg PO or IV q24h, and (2) azithromycin 500 mg IV q24h for > or = 2 days plus ceftriaxone 1 g IV q24h for 2 days, followed by an optional transition to azithromycin 500 mg PO q24h at the investigators discretion. The total duration of therapy was to be a minimum of 10 days in both treatment groups. Ceftriaxone was included in the initial azithromycin regimen to ensure coverage against pneumococcal bacteremia. RESULTS Of 236 patients in the intent-to-treat population, completion or withdrawal information was available for 110 patients in the levofloxacin group and 114 in the azithromycin group. Baseline demographic and disease characteristics were comparable between groups. At the end of treatment, the clinical success rate (cured + improved) in clinically evaluable patients was 94.1% in the levofloxacin group and 92.3% in the azithromycin group. The respective posttherapy microbiologic eradication rates were 89.5% and 92.3%. Levofloxacin was as well tolerated as azithromycin, with an incidence of drug-related adverse events (AEs) for all body systems of 5.3% and 9.3%, respectively. None of the drug-related AEs were considered serious [corrected]. CONCLUSIONS In this study in hospitalized patients with moderate to severe CAP, levofloxacin monotherapy was at least as effective as a combination regimen of azithromycin and ceftriaxone in providing coverage against the current causative pathogens in CAP. In addition, levofloxacin was as well tolerated as the combination of azithromycin and ceftriaxone.

Time course of adverse events most commonly associated with topiramate for migraine prevention

The efficacy, safety and tolerability of topiramate has been demonstrated in three large multicenter, randomized, double‐blind, placebo‐controlled trials. To characterize the time course of adverse events (AEs) that led to treatment discontinuation in ≥2% of patients who received topiramate 100 mg/day during three pivotal, multicenter, randomized, double‐blind, placebo‐controlled, and 26‐week trials. The pooled population comprised all randomized patients who reported safety data during the double‐blind phase (topiramate 100 mg/day, n = 386; placebo n = 372), which consisted of a 4‐week titration period and a 22‐week maintenance period. Incidence, time to onset, and cumulative mean rate of AEs were assessed. Overall, AEs led to treatment discontinuation in 24.9% of patients receiving topiramate 100 mg/day and 11.0% receiving placebo (P < 0.001). AEs leading to discontinuation during the double‐blind phase in ≥2% of patients included paresthesia (8.0% discontinued), any cognitive symptoms (7.3% discontinued), fatigue (4.7% discontinued), insomnia (3.4% discontinued), nausea (2.3% discontinued), loss of appetite, anxiety, and dizziness (2.1% discontinued because each AE). Most AEs began during the titration period. Paresthesia, any cognitive symptoms, nausea, and loss of appetite occurred at a higher rate in the topiramate group than in the placebo group (P < 0.01). AEs leading to discontinuation of topiramate are probably to occur during dose titration. If a patient has not experienced one of these AEs within the first 6 weeks of initiating topiramate 100 mg/day, these AEs are unlikely to occur.

Estimating the economic impact of a half-day reduction in length of hospital stay among patients with community-acquired pneumonia in the US

ABSTRACT Background: A recent study suggested that levofloxacin significantly reduces the hospital length of stay (LOS), by 0.5 days (p = 0.02), relative to moxifloxacin in patients with community-acquired pneumonia (CAP). The current analysis evaluated the potential economic impact of this half-day reduction in LOS. Methods: A cost model was developed to estimate the impact of a half-day reduction in LOS for CAP hospitalizations in the US. CAP incidence, hospitalization rate, and costs were obtained from published studies in PubMed and from publicly available government sources. The average daily cost of hospitalization was estimated for fixed costs, which comprise 59% of total inpatient costs. Costs from prior years were inflated to 2007 US dollars using the consumer price index. A range of cost savings, calculated using inpatient CAP costs from several studies, was extrapolated to the US CAP population. Results: Using the Centers for Disease Control National Hospital Discharge estimate of 5.3 days LOS for CAP, and an average cost (2007

Topiramate intervention to prevent transformation of episodic migraine: the topiramate INTREPID study.

US) of

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

13,009 per CAP hospitalization, a daily fixed cost of

A comparison of levofloxacin and moxifloxacin use in hospitalized community-acquired pneumonia (CAP) patients in the US: focus on length of stay

1448 was estimated. The resultant half-day reduction in costs associated with LOS was

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

724/hospitalization (range

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

457 to

Development and validation of a new instrument to evaluate the ease of use of patient-controlled analgesic modalities for postoperative patients

846/hospitalization). When fixed and variable costs were considered, the estimated savings were