Chris Worrall

Cardiovascular, Bleeding, and Mortality Risks in Elderly Medicare Patients Treated With Dabigatran or Warfarin for Nonvalvular Atrial Fibrillation

Background— The comparative safety of dabigatran versus warfarin for treatment of nonvalvular atrial fibrillation in general practice settings has not been established. Methods and Results— We formed new-user cohorts of propensity score–matched elderly patients enrolled in Medicare who initiated dabigatran or warfarin for treatment of nonvalvular atrial fibrillation between October 2010 and December 2012. Among 134 414 patients with 37 587 person-years of follow-up, there were 2715 primary outcome events. The hazard ratios (95% confidence intervals) comparing dabigatran with warfarin (reference) were as follows: ischemic stroke, 0.80 (0.67–0.96); intracranial hemorrhage, 0.34 (0.26–0.46); major gastrointestinal bleeding, 1.28 (1.14–1.44); acute myocardial infarction, 0.92 (0.78–1.08); and death, 0.86 (0.77–0.96). In the subgroup treated with dabigatran 75 mg twice daily, there was no difference in risk compared with warfarin for any outcome except intracranial hemorrhage, in which case dabigatran risk was reduced. Most patients treated with dabigatran 75 mg twice daily appeared not to have severe renal impairment, the intended population for this dose. In the dabigatran 150-mg twice daily subgroup, the magnitude of effect for each outcome was greater than in the combined-dose analysis. Conclusions— In general practice settings, dabigatran was associated with reduced risk of ischemic stroke, intracranial hemorrhage, and death and increased risk of major gastrointestinal hemorrhage compared with warfarin in elderly patients with nonvalvular atrial fibrillation. These associations were most pronounced in patients treated with dabigatran 150 mg twice daily, whereas the association of 75 mg twice daily with study outcomes was indistinguishable from warfarin except for a lower risk of intracranial hemorrhage with dabigatran.

Stroke, Bleeding, and Mortality Risks in Elderly Medicare Beneficiaries Treated With Dabigatran or Rivaroxaban for Nonvalvular Atrial Fibrillation

Importance Dabigatran and rivaroxaban are non-vitamin K oral anticoagulants approved for stroke prevention in patients with nonvalvular atrial fibrillation (AF). There are no randomized head-to-head comparisons of these drugs for stroke, bleeding, or mortality outcomes. Objective To compare risks of thromboembolic stroke, intracranial hemorrhage (ICH), major extracranial bleeding including major gastrointestinal bleeding, and mortality in patients with nonvalvular AF who initiated dabigatran or rivaroxaban treatment for stroke prevention. Design, Setting, and Participants Retrospective new-user cohort study of 118 891 patients with nonvalvular AF who were 65 years or older, enrolled in fee-for-service Medicare, and who initiated treatment with dabigatran or rivaroxaban from November 4, 2011, through June 30, 2014. Differences in baseline characteristics were adjusted using stabilized inverse probability of treatment weights based on propensity scores. The data analysis was performed from May 7, 2015, through June 30, 2016. Exposures Dabigatran, 150 mg, twice daily; rivaroxaban, 20 mg, once daily. Main Outcomes and Measures Adjusted hazard ratios (HRs) for the primary outcomes of thromboembolic stroke, ICH, major extracranial bleeding including major gastrointestinal bleeding, and mortality, with dabigatran as reference. Adjusted incidence rate differences (AIRDs) were also estimated. Results A total of 52 240 dabigatran-treated and 66 651 rivaroxaban-treated patients (47% female) contributed 15 524 and 20 199 person-years of on-treatment follow-up, respectively, during which 2537 primary outcome events occurred. Rivaroxaban use was associated with a statistically nonsignificant reduction in thromboembolic stroke (HR, 0.81; 95% CI, 0.65-1.01; P = .07; AIRD = 1.8 fewer cases/1000 person-years), statistically significant increases in ICH (HR, 1.65; 95% CI, 1.20-2.26; P = .002; AIRD = 2.3 excess cases/1000 person-years) and major extracranial bleeding (HR, 1.48; 95% CI, 1.32-1.67; P < .001; AIRD = 13.0 excess cases/1000 person-years), including major gastrointestinal bleeding (HR, 1.40; 95% CI, 1.23-1.59; P < .001; AIRD = 9.4 excess cases/1000 person-years), and with a statistically nonsignificant increase in mortality (HR, 1.15; 95% CI, 1.00-1.32; P = .051; AIRD = 3.1 excess cases/1000 person-years). In patients 75 years or older or with CHADS2 score greater than 2, rivaroxaban use was associated with significantly increased mortality compared with dabigatran use. The excess rate of ICH with rivaroxaban use exceeded its reduced rate of thromboembolic stroke. Conclusions and Relevance Treatment with rivaroxaban 20 mg once daily was associated with statistically significant increases in ICH and major extracranial bleeding, including major gastrointestinal bleeding, compared with dabigatran 150 mg twice daily.

Comparative effectiveness of high-dose versus standard-dose influenza vaccines in US residents aged 65 years and older from 2012 to 2013 using Medicare data: a retrospective cohort analysis

BACKGROUND A high-dose trivalent inactivated influenza vaccine was licensed in 2009 by the US Food and Drug Administration (FDA) on the basis of serological criteria. We sought to establish whether high-dose inactivated influenza vaccine was more effective for prevention of influenza-related visits and hospital admissions in US Medicare beneficiaries than was standard-dose inactivated influenza vaccine. METHODS In this retrospective cohort study, we identified Medicare beneficiaries aged 65 years and older who received high-dose or standard-dose inactivated influenza vaccines from community pharmacies that offered both vaccines during the 2012-13 influenza season. Outcomes were defined with billing codes on Medicare claims. The primary outcome was probable influenza infection, defined by receipt of a rapid influenza test followed by dispensing of the neuraminidase inhibitor oseltamivir. The secondary outcome was a hospital or emergency department visit, listing a Medicare billing code for influenza. We estimated relative vaccine effectiveness by comparing outcome rates in Medicare beneficiaries during periods of high influenza circulation. Univariate and multivariate Poisson regression models were used for analyses. FINDINGS Between Aug 1, 2012 and Jan 31, 2013, we studied 929,730 recipients of high-dose vaccine and 1,615,545 recipients of standard-dose vaccine. Participants enrolled in each cohort were well balanced with respect to age and presence of underlying medical disorders. The high-dose vaccine (1·30 outcomes per 10,000 person-weeks) was 22% (95% CI 15-29) more effective than the standard-dose vaccine (1·01 outcomes per 10,000 person-weeks) for prevention of probable influenza infections (rapid influenza test followed by oseltamivir treatment) and 22% (95% CI 16-27%) more effective for prevention of influenza hospital admissions (0·86 outcomes per 10,000 person-weeks in the high-dose cohort vs 1·10 outcomes per 10,000 person-weeks in the standard-dose cohort). INTERPRETATION Our retrospective cohort study in US Medicare beneficiaries shows that, in people 65 years of age and older, high-dose inactivated influenza vaccine was significantly more effective than standard-dose vaccine in prevention of influenza-related medical encounters. Additionally, the large population in our study enabled us to show, for the first time, a significant reduction in influenza-related hospital admissions in high-dose compared to standard-dose vaccine recipients, an outcome not shown in randomised studies. These results provide important new information to be considered by policy makers recommending influenza vaccinations for elderly people. FUNDING FDA and the office of the Assistant Secretary of Planning and Evaluation.

Comparative Risk of Anaphylactic Reactions Associated With Intravenous Iron Products

IMPORTANCE All intravenous (IV) iron products are associated with anaphylaxis, but the comparative safety of each product has not been well established. OBJECTIVE To compare the risk of anaphylaxis among marketed IV iron products. DESIGN, SETTING, AND PARTICIPANTS Retrospective new user cohort study of IV iron recipients (n = 688,183) enrolled in the US fee-for-service Medicare program from January 2003 to December 2013. Analyses involving ferumoxytol were limited to the period January 2010 to December 2013. EXPOSURES Administrations of IV iron dextran, gluconate, sucrose, or ferumoxytol as reported in outpatient Medicare claims data. MAIN OUTCOMES AND MEASURES Anaphylaxis was identified using a prespecified and validated algorithm defined with standard diagnosis and procedure codes and applied to both inpatient and outpatient Medicare claims. The absolute and relative risks of anaphylaxis were estimated, adjusting for imbalances among treatment groups. RESULTS A total of 274 anaphylaxis cases were identified at first exposure, with an additional 170 incident anaphylaxis cases identified during subsequent IV iron administrations. The risk for anaphylaxis at first exposure was 68 per 100,000 persons for iron dextran (95% CI, 57.8-78.7 per 100,000) and 24 per 100,000 persons for all nondextran IV iron products combined (iron sucrose, gluconate, and ferumoxytol) (95% CI, 20.0-29.5 per 100,000) , with an adjusted odds ratio (OR) of 2.6 (95% CI, 2.0-3.3; P < .001). At first exposure, when compared with iron sucrose, the adjusted OR of anaphylaxis for iron dextran was 3.6 (95% CI, 2.4-5.4); for iron gluconate, 2.0 (95% CI 1.2, 3.5); and for ferumoxytol, 2.2 (95% CI, 1.1-4.3). The estimated cumulative anaphylaxis risk following total iron repletion of 1000 mg administered within a 12-week period was highest with iron dextran (82 per 100,000 persons, 95% CI, 70.5- 93.1) and lowest with iron sucrose (21 per 100,000 persons, 95% CI, 15.3- 26.4). CONCLUSIONS AND RELEVANCE Among patients in the US Medicare nondialysis population with first exposure to IV iron, the risk of anaphylaxis was highest for iron dextran and lowest for iron sucrose.

Comparative Effectiveness of High-Dose Versus Standard-Dose Influenza Vaccines Among US Medicare Beneficiaries in Preventing Postinfluenza Deaths During 2012-2013 and 2013-2014.

Background Recipients of high-dose vs standard-dose influenza vaccines have fewer influenza illnesses. We evaluated the comparative effectiveness of high-dose vaccine in preventing postinfluenza deaths during 2012-2013 and 2013-2014, when influenza viruses and vaccines were similar. Methods We identified Medicare beneficiaries aged ≥65 years who received high-dose or standard-dose vaccines in community-located pharmacies offering both vaccines. The primary outcome was death in the 30 days following an inpatient or emergency department encounter listing an influenza International of Classification of Diseases, Ninth Revision, Clinical Modification code. Effectiveness was estimated by using multivariate Poisson regression models; effectiveness was allowed to vary by season. Results We studied 1039645 recipients of high-dose and 1683264 recipients of standard-dose vaccines during 2012-2013, and 1508176 high-dose and 1877327 standard-dose recipients during 2013-2014. Vaccinees were well-balanced for medical conditions and indicators of frail health. Rates of postinfluenza death were 0.028 and 0.038/10000 person-weeks in high-dose and standard-dose recipients, respectively. Comparative effectiveness was 24.0% (95% confidence interval [CI], .6%-42%); there was evidence of variation by season (P = .12). In 2012-2013, high-dose was 36.4% (95% CI, 9.0%-56%) more effective in reducing mortality; in 2013-2014, it was 2.5% (95% CI, -47% to 35%). Conclusions High-dose vaccine was significantly more effective in preventing postinfluenza deaths in 2012-2013, when A(H3N2) circulation was common, but not in 2013-2014.

The complexity of disease combinations in the Medicare population.

Developing systems of care that address the mortality, morbidity, and expenditures associated with Medicare beneficiaries with multiple diseases would benefit from a greater understanding of the complexity of disease combinations (DCs) found in the Medicare population. To develop estimates of the number of DCs, we performed an observational analysis on 32,220,634 beneficiaries in the Medicare Fee-for-Service claims database based on a set of records containing each beneficiarys Part A and B International Classification of Diseases, 9(th) Revision, Clinical Modification (ICD-9-CM) claims data for the year of 2008. We made 2 simplifying adjustments. First, we mapped the individual ICD-9-CM codes to the Centers for Medicare and Medicaid Services-Hierarchical Conditions Categories (HCC) model that was developed in 2004 to risk adjust capitation payments to private health care plans based on the health expenditure risk of their enrollees. Second, we aggregated beneficiaries with identical HCCs regardless of the temporal order of these findings within the 2008 claims year; thus the DC to which they are assigned represents the summation of their 2008 claims data. We defined 3 distinct populations at the HCC level. The first consisted of 35% of the beneficiaries who did not fall into any HCC category and accounted for 6% of expenditures. The second was represented by the 100 next most prevalent DCs that accounted for 33% of the beneficiaries and 15% of expenditures. The final population, accounting for 32% of the beneficiaries and 79% of expenses, was complex and consisted of over 2 million DCs. Our results indicate that the majority of expenditures are associated with a complex set of beneficiaries.

Using Medicare Data to Identify Individuals Who Are Electricity Dependent to Improve Disaster Preparedness and Response

During a disaster or prolonged power outage, individuals who use electricity-dependent medical equipment are often unable to operate it and seek care in acute care settings or local shelters. Public health officials often report that they do not have proactive and systematic ways to rapidly identify and assist these individuals. In June 2013, we piloted a first-in-the-nation emergency preparedness drill in which we used Medicare claims data to identify individuals with electricity-dependent durable medical equipment during a disaster and securely disclosed it to a local health department. We found that Medicare claims data were 93% accurate in identifying individuals using a home oxygen concentrator or ventilator. The drill findings suggest that claims data can be useful in improving preparedness and response for electricity-dependent populations.

Effectiveness and Duration of Protection Provided by the Live-attenuated Herpes Zoster Vaccine in the Medicare Population Ages 65 Years and Older

Background Tens of millions of seniors are at risk of herpes zoster (HZ) and its complications. Live attenuated herpes zoster vaccine (HZV) reduces that risk, although questions regarding effectiveness and durability of protection in routine clinical practice remain. We used Medicare data to investigate HZV effectiveness (VE) and its durability. Methods This retrospective cohort study included beneficiaries ages ≥65 years during January 2007 through July 2014. Multiple adjustments to account for potential bias were made. HZV-vaccinated beneficiaries were matched to unvaccinated beneficiaries (primary analysis) and to HZV-unvaccinated beneficiaries who had received pneumococcal vaccination (secondary analysis). HZ outcomes in community and hospital settings were analyzed, including ophthalmic zoster (OZ) and postherpetic neuralgia (PHN). Results Among eligible beneficiaries (average age 77 years), the primary analysis found VE for community HZ of 33% (95% CI: 32%-35%) and 19% (95% CI: 17%-22%), for the first 3, and subsequent 4+ years postvaccination, respectively. In the secondary analysis, VE was, respectively, 37% (95% CI: 36%-39%) and 22% (95% CI: 20%-25%). In the primary analysis, VE for PHN was 57% (95% CI: 52%-61%) and 45% (95% CI: 36%-53%) in the first 3 and subsequent 4+ years, respectively; VE for hospitalized HZ was, respectively, 74% (95% CI: 67%-79%) and 55% (95% CI: 39%-67%). Differences in VE by age group were not significant. Conclusions In both the primary and secondary analyses, HZV provided protection against HZ across all ages, but effectiveness declined over time. VE was higher and better preserved over time for PHN and HZ-associated hospitalizations than for community HZ.

Early Mortality After Aortic Valve Replacement With Mechanical Prosthetic vs Bioprosthetic Valves Among Medicare Beneficiaries: A Population-Based Cohort Study

IMPORTANCE Early mortality for patients who undergo aortic valve replacement (AVR) may differ between mechanical and biological prosthetic (hereinafter referred to as bioprosthetic) valves. Clinical trials may have difficulty addressing this issue owing to limited sample sizes and low mortality rates. OBJECTIVE To compare early mortality after AVR between the recipients of mechanical and bioprosthetic aortic valves. DESIGN, SETTING, AND PARTICIPANTS A retrospective analysis of patients 65 years or older in the Medicare databases who underwent AVR from July 1, 2006, through December 31, 2011. In the mixed-effects models adjusting for physician and hospital random effects, we estimated odds ratios (OR) of early mortality to compare mechanical vs bioprosthetic valves. EXPOSURES Mechanical or bioprostheticaortic valve replacement. MAIN OUTCOMES AND MEASURES Early mortality was measured as death on the date of surgery, death within 1 to 30 or 31 to 365 days after the date of surgery, death within 30 days after the date of hospital discharge, and operative mortality (death within 30 days after surgery or at discharge, whichever is longer). RESULTS Of the 66 453 Medicare beneficiaries who met inclusion criteria, 19 190 (28.88%) received a mechanical valve and 47 263 (71.12%) received a bioprosthetic valve. The risk for death on the date of surgery was 60% higher for recipients of mechanical valves than recipients of bioprosthetic valves (OR, 1.61 [95% CI, 1.27-2.04; P < .001]; risk ratio [RR], 1.60). The risk difference decreased to 16% during the 30 days after the date of surgery (OR, 1.18 [95% CI, 1.09-1.28; P < .001]; RR, 1.16). We found no differences within 31 to 365 days after the date of surgery and within the 30 days after discharge. The risk for operative mortality was 19% higher for recipients of mechanical compared with bioprosthetic valves (OR, 1.21 [95% CI, 1.13-1.30; P < .001]; RR, 1.19). The number needed to treat with mechanical valves to observe 1 additional death on the surgery date was 290; to observe 1 additional death within 30 days of surgery, 121. Consistent findings were observed in subgroup analyses of patients who underwent concurrent AVR and coronary artery bypass graft, but not in the subgroup undergoing isolated AVR. CONCLUSIONS AND RELEVANCE In this cohort analysis of Medicare beneficiaries, use of mechanical aortic valves was associated with a higher risk for death on the date of surgery and within the 30 days after surgery compared with bioprosthetic aortic valves among patients who underwent concurrent AVR and coronary artery bypass graft but not isolated AVR.

Cardiovascular and mortality risk in elderly Medicare beneficiaries treated with olmesartan versus other angiotensin receptor blockers.

In the randomized trial, Randomized Olmesartan and Diabetes Microalbuminuria Prevention, acute cardiovascular death was increased nearly fivefold in diabetic patients treated with high‐dose olmesartan, an angiotensin receptor blocker (ARB), compared with placebo.