Baseline characteristics and secondary medication adherence among Medicare patients diagnosed with transthyretin amyloid cardiomyopathy and/or receiving tafamidis prescriptions: A retrospective analysis of a Medicare cohort.

BACKGROUND: Transthyretin amyloid cardiomyopathy (ATTR-CM) is an underdiagnosed, life-threatening condition that mostly affects older persons. In May 2019, regulatory approval of tafamidis provided the first pharmacologic treatment of ATTR-CM. In the pivotal phase 3 Transthyretin Amyloidosis Cardiomyopathy Clinical Trial (ATTR-ACT), 97.2% of patients were classified as adherent (defined as taking ≥ 80% of scheduled doses). Given its recent approval, there is limited real-world evidence examining patient adherence to tafamidis. OBJECTIVE: To evaluate adherence patterns, demographics, and clinical characteristics of patients in the United States receiving tafamidis prescriptions through Medicare. Secondarily, we aimed to evaluate concomitant medications filled by this patient population. METHODS: We conducted a retrospective cohort study of US Medicare claims data, limited by the Health Insurance Portability and Accountability Act of 1996, in adult patients with an adjudicated pharmacy claim for tafamidis (tafamidis free acid 61-mg capsule once daily or tafamidis meglumine four 20-mg capsules once daily) between May 1, 2019, and June 30, 2021. Gaps in therapy were measured using day gaps between prescription refills and continuous measure of medication gaps. Implementation adherence was assessed through modified medication possession ratio (MPRm), medication refill adherence (MRA), and proportion of days covered (PDC). Patients were grouped based on Medicare coverage. Patients were analyzed by subgroups based on age and at the zip code level, via distressed communities index quartiles and rural-urban tiers. RESULTS: A total of 3,558 patients who received a prescription fill of a tafamidis formulation were identified using Medicare Fee-for-Service (FFS) and Medicare Advantage (MA) claims data from May 1, 2019, to June 30, 2021. The characteristics of this patient population were consistent with published literature, as 98.6% were older than 65 years, 53.4% were between 75 years and 84 years, and 81.5% were male. In the patient population receiving tafamidis refills, adherence was high across all 3 measures, with mean MPRm greater than 90% and mean MRA greater than 80%, across all age groups. Mean PDC adherence rates were 79% or more across all age groups. Concomitant medications were generally indicated for heart failure and thrombosis. Among monotherapy groups with similar demographic makeup, adherence was significantly higher among users of tafamidis free acid vs tafamidis meglumine (P < 0.0001 across all mean adherence measures). CONCLUSIONS: Our results demonstrate that real-world adherence to tafamidis in the Medicare population is high, regardless of age, zip code-level socioeconomic quartile, or geography. Adherence was higher among patients receiving tafamidis free acid, suggesting that the enhanced convenience of a single capsule once daily may positively contribute to adherence among patients with ATTR-CM. DISCLOSURES: Darrin Benjumea is an employee of Genesis Research who has been contracted by Pfizer, Inc., for involvement in this study. Andrew Peterson is an employee of University of the Sciences who has been contracted by Pfizer, Inc., for involvement in this study. Zach Bredl is an employee of Care Journey who has been contracted by Pfizer, Inc., for involvement in this study. Anuja Roy, Nick Marchant, Jose Alvir, Rahul Bhambri, Jason Kemner, and Bhash Parasuraman are employees of Pfizer, Inc., and own stock and/or stock options. This study was supported by Pfizer, Inc.

Baseline Characteristics and Secondary Medication Adherence Patterns Among Patients Receiving Tafamidis Prescriptions: A Retrospective Analysis Using a National Specialty Pharmacy Dispensing Database.

Introduction: Transthyretin amyloid cardiomyopathy (ATTR-CM) is a serious, underrecognized condition, which leads to heart failure and early mortality if left untreated. Until recently, heart transplantation was the only treatment for ATTR-CM. Regulatory approval of tafamidis transformed treatment for patients. In the phase 3 Transthyretin Amyloidosis Cardiomyopathy Clinical Trial (ATTR-ACT), which established the safety and efficacy of tafamidis, medication adherence was high with 97.2% of patients taking ≥80% of scheduled doses. Evidence of real-world adherence to cardiology drugs demonstrates low adherence and suboptimal outcomes; however, real-world adherence to tafamidis has not been investigated. The main objective of this study was to describe adherence patterns of patients filling tafamidis in the Symphony Health database. Methods: This retrospective analysis of the Symphony Health Solutions claims database used secondary adherence measures, including modified medication possession ratio (MPRm), days between fills adherence rate, and compliance rate, to assess adherence patterns of 2020 patients filling tafamidis free acid 61-mg capsules or tafamidis meglumine 4x20-mg capsules from June 1, 2019 to August 31, 2020. Results: Patients receiving a tafamidis formulation had characteristics consistent with the expected patient population; 71.6% were aged 75-84 years, 83.2% were male, and the highest proportion resided in the Northeast region (30.5%) of the United States. Adherence for tafamidis was high, as 75% to 100% of the patients across subgroups met or exceeded the commonly defined adherence threshold of 80%. Median number of refills ordered and received was six refills per patient. Most patients received refills with no gap (n=1633) or a gap <30 days (n=1267/1317 patients). Adherence was high across follow-up time, sex, and age subgroups. Adherence varied by geographic region, with the Northeast being significantly higher than the Midwest (mean MPRm 94.41% vs 88.21%, p=0.0007). Conclusion: These results provide evidence that real-world adherence to tafamidis in patients with ATTR-CM is high.

Healthcare Costs of Smokers Using Varenicline Versus Nicotine-Replacement Therapy Patch in the United States: Evidence from Real-World Practice.

INTRODUCTION: Varenicline (VAR) is an effective smoking-cessation therapy compared to the commonly used nicotine-replacement therapy patch (NRT-P). However, comparative real-world evidence on smoking-cessation therapies is limited, especially for economic outcomes. METHODS: Using national claims databases (2012-2016) in the United States (US), adults initiating VAR or NRT-P without use of any other smoking-cessation products were followed for up to 1 year on a quarterly basis. Outcomes included smoking-attributable (SA) (cardiovascular, diabetes, pulmonary diseases, and smoking cessation) and all-cause costs (2017 US dollars). Adjusted mean costs were estimated from multivariable regressions, with baseline characteristics and propensity scores as covariates. Annual adjusted costs were calculated from quarterly averages. RESULTS: The VAR cohort (n = 209,284) was younger (mean age 46.7 vs. 49.0 years) and had fewer comorbidities [mean Charlson Comorbidity Index (CCI): 0.8 vs. 1.6] than the NRT-P cohort (n = 34,593). After adjustment, VAR cohort had lower SA and all-cause medical costs than NRT-P cohort in Quarters 1-4 (Q1-Q4) of follow-up, and had lower SA and all-cause total costs in Q2-Q4. Annually, VAR cohort had higher SA total costs ($307) and lower all-cause costs (- $2089) than NRT-P cohort. Annual medical costs were lower in VAR cohort (- $640 for SA and - $2876 for all-cause), and pharmacy costs were higher ($762 for SA and $777 for all-cause). In adherent patients (VAR: n = 38,744; NRT-P: n = 2702), VAR patients had lower annual medical costs (- $794 for SA and - $1636 for all-cause) and higher pharmacy costs ($1175 for SA and $1269 for all-cause); differences in SA and all-cause total costs were not statistically significant between treatment groups. CONCLUSIONS: Lower SA and all-cause medical costs associated with the use of VAR versus NRT-P resulted in savings in all-cause total costs and, among adherent patients, potentially offset the high pharmacy costs of VAR. FUNDING: Pfizer, Inc.

Vitamin K antagonist treatment in patients with atrial fibrillation and time in therapeutic range in four European countries.

PURPOSE: Patients with atrial fibrillation are at increased risk for stroke and thus require anticoagulant prophylaxis with vitamin K antagonists. However, many such patients fail to achieve target coagulation status. The objective of this study was to evaluate time in the therapeutic range and its relationship to clinical outcomes in patients with nonvalvular atrial fibrillation prescribed a vitamin K antagonist in everyday clinical practice in 4 European countries (France, Germany, Italy and the United Kingdom). METHODS: Data were extracted from the European electronic primary care database, the Longitudinal Patient Database. Included in the analysis were 6250 adult patients for whom data on monitoring of coagulation time and international normalized ratio were available. The time within the therapeutic range was estimated by using the Rosendaal method. Patients spending >70% of time within the therapeutic range were considered to have well-controlled treatment. Data on stroke and bleeding events occurring during the study period were taken from patient records. Stroke risk was calculated by using the CHA2DS2-VASc score (i.e. 2 points for a history of stroke or TIA and age >75 years, and 1 point for age between 65 and 74 years, hypertension, diabetes mellitus, a recent cardiac failure, vascular disease and female sex). FINDINGS: The proportion of patients with poorly controlled treatment varied from 34.6% in the United Kingdom to 55.8% in Germany. The incidence of stroke was 0.5/100 person-years in well-controlled patients, compared with 1.0/100 in poorly controlled patients. After adjustment for stroke risk factors, the odds ratio was 1.38 (95% CI, 0.93-2.06; P = 0.110). The incidence of hemorrhage was 1.1 and 1.3 events/100 person-years, respectively (odds ratio, 0.91 [95% CI, 0.72-1.16]). IMPLICATIONS: Many patients receiving prophylaxis with vitamin K antagonists in everyday community care have poorly controlled anticoagulation treatment with vitamin K antagonists. Their international normalized ratio is frequently outside the therapeutic range, and they are thus exposed to an unnecessary risk of stroke or bleeding complications.

The efficacy and safety of pharmacological prophylaxis of venous thromboembolism following elective knee or hip replacement: systematic review and network meta-analysis.

The present systematic review was conducted to assess the efficacy and safety of apixaban versus other anticoagulants, for the prevention of venous thromboembolism (VTE) following total hip replacement (THR) and total knee replacement (TKR) surgery. Electronic databases were interrogated to identify relevant randomized controlled trials. A series of direct/indirect comparisons and a network meta-analysis were conducted. Indirect comparisons found that the odds ratio of "all VTE and all-cause death" were significantly higher for dabigatran than for apixaban in patients with THR (odds ratio [OR], 2.51; 95% confidence interval [CI], 1.50-4.21) and TKR (OR, 1.72; 95% CI, 1.22-2.42). Rivaroxaban showed similar efficacy to apixaban in patients with THR and TKR (OR, 0.69; 95% CI, 0.38-1.25 and OR, 0.83; 95% CI, 0.57-1.19, respectively). No significant differences were observed in bleeding outcomes between treatments. The novel anticoagulants apixaban, rivaroxaban, and dabigatran demonstrated similar or improved efficacy and similar safety compared with current therapies in this indication.

Preferences of patients with diabetes mellitus for inhaled versus injectable insulin regimens.

BACKGROUND: In clinical trials, patients have expressed greater satisfaction with inhaled human insulin (EXUBERA, Pfizer) than with injectable insulin. No studies to date have attempted to quantify the strength of preferences for these alternative routes of administration. OBJECTIVE: To elicit health state preference values from people with diabetes mellitus for treatment with inhaled human insulin compared with injectable insulin. STUDY DESIGN: A patient preference study. METHODS: Written descriptions were developed for five clinical scenarios: two for type 1 diabetes and three for type 2 diabetes. Each scenario required adjustment or initiation of insulin treatment because of poor glycaemic control. Two alternative insulin regimens were described for each scenario: injectable-only or inhaled human insulin to replace or reduce the number of daily injections. Equal efficacy was assumed within each of these scenario pairs.A total of 344 UK adults (66% male), 132 (mean age 49 years) with type 1 diabetes and 212 (mean age 63 years) with type 2 diabetes, rated scenario pairs corresponding to their own type of diabetes and rated their own health by time trade-off (TTO), by correspondence with EQ-5D health descriptions and on the EQ-5D visual analogue scale. Respondents stated their preference for, or indifference between, the injection-only or inhalation variant comprising each scenario pair. TTO utilities and EQ-5D utilities by UK community tariff were compared within each scenario pair, for the total sample rating, each scenario pair, and by subgroups of stated preference for each variant. RESULTS: A majority, ranging from 63% to 81% across the scenarios, preferred inhalation. Mean differences in TTO scores were 0.074, 0.076, 0.088, 0.053 and 0.043 for the five scenarios, respectively (p < 0.005 for all). Mean EQ-5D differences were 0.043, 0.029, 0.037, 0.020 and 0.021 for the five scenarios, respectively (p < 0.05 for scenarios 1 and 3), driven mainly by differences on the pain/discomfort dimension of the EQ-5D. Differences in favour of inhalation among those preferring inhalation, were greater than differences in favour of injections among those preferring injections. Mean self-rated health was similar between respondents with type 1 and type 2 diabetes, at 0.83 (TTO) and 0.75 (EQ-5D). The TTO was more sensitive than EQ-5D. Self-rated health by EQ-5D compared closely with reported values from the UK Prospective Diabetes Study (UKPDS). CONCLUSIONS: This study highlights the utility differences that people with diabetes perceive between the prospect of inhaled and injected routes of insulin administration, even under the assumption of no difference in efficacy. These differences are magnified when the comparison in utility scores is between the majority who prefer the inhaled route and the minority who prefer the injectable route.

The financial costs of hospital care for people with diabetes who have single and multiple macrovascular complications.

AIM: To evaluate the impact on hospital costs of patients being diagnosed with multiple complications of diabetes. METHODS: All inpatient admissions and outpatient appointments from the Cardiff and Vale of Glamorgan area (1996 onwards) were cross-referenced to the diabetes register. Each episode of inpatient care was coded using Healthcare Resource Group (HRG) grouper software. The allocated HRG-coded episode was linked to a series of elective and emergency reference costs from the National Health Service costing manual. Outpatient appointments were cost-coded using the mean reference costs by specialty. Non-psychiatric finished consultant episodes (FCEs) were used rather than admissions to report inpatient utilisation. RESULTS: Overall, 2815 of the total 10,287 patients identified as inpatients had at least one admission; 6133 admissions (finished consultant episodes) were successfully grouped to give a total estimated cost of pound sterling 7,373,539. An incremental, linear relationship was observed in the cost increases for each additional diagnosed complication. Mean annual inpatient age-standardised costs were pound sterling 434 for no complications, pound sterling 999 for one complication, pound sterling 1,641 for two, and pound sterling 2,462 for three. There were 5717 patients with diabetes who attended 25,334 outpatient appointments. The estimated cost for these outpatient appointments was pound sterling 1,833,232. CONCLUSION: Minimising the number of complications in patients with diabetes would result in considerable cost offsets.

Comparative estimates of the financial burden to the UK health system of hospital care for people with and without diabetes in the year before death.

OBJECTIVE: To quantify hospital costs prior to death for patients with and without diabetes. RESEARCH DESIGN AND METHODS: Using the Cardiff Diabetes Database, mortality data from the UK Office of National Statistics for 1996 were linked to existing hospital records using probability matching techniques. Costs were attributed using a statistical costing technique (healthcare resource groups (HRGs)) with UK 2000 prices. RESULTS: There were 4394 deaths of which 412 (9.4%) were for patients with diabetes. In the year before death 380 (92%) patients with diabetes (DM+) were admitted as an inpatient compared with 73% of those without diabetes (DM-), a relative rate of 1.27. Total inpatient costs were 12.2M UK pound sterling (20M US dollars) of which costs for patients with diabetes were 1.6M UK pound sterling (2.6M US dollars), accounting for 15.6% of revenue. This translates to a rate of 2.8M UK pound sterling (4.0M US dollars) per 100,000 population per year. The mean annual inpatient cost before death was UK pound 3997 (5676 US dollars) for DM+ compared with UK pound 2656 (3772 US dollars) for DM-. Mean annual outpatient costs ranged from 185 UK pound sterling (263 US dollars: year minus 4) to 248 UK pound sterling (352 US dollars: year minus 2) in DM+, and 91 UK pound sterling (129 US dollars: year minus 4) to 116 UK pound sterling (165 US dollars: year minus 2) in DM-. Mean annual outpatient costs associated with the care of people with diabetes are consistently higher: +80% at minus 1-year rising to +120% at minus 3 years. CONCLUSIONS: The costs of inpatient care for all patients increases markedly in the final year of life. People with diabetes were found to be more financially costly, even in this stage of their care, than were people who did not have diabetes.

Financial and health costs of uncontrolled blood pressure in the United Kingdom.

BACKGROUND: Uncontrolled hypertension is associated with an elevated risk of all cardiovascular disease, especially stroke. However, many patients with hypertension do not achieve agreed targets for blood pressure. OBJECTIVE: To estimate the cost and morbidity consequences of uncontrolled hypertension in the UK. DESIGN: Descriptive epidemiological study. METHODS: The study used a burden-of-disease model combining data on the prevalence of hypertension, the incidence of major cardiovascular (CV) events and the costs of treating these events. The prevalence of uncontrolled hypertension was taken from the 1998 Health Survey for England. The incidences of three CV events, acute myocardial infarction, congestive heart failure and stroke, at different levels of achieved blood pressure, were estimated using results from the Hypertension Optimal Treatment study. Costs were taken from published sources. We estimated the number of major CV events and acute hospital costs that would be avoided if all people with hypertension had blood pressure treated to target levels. RESULTS: The model estimated that in the UK 5.7 million adults (12% of the population aged >16 years) have actual blood pressure above 160/95 mm Hg, and a further 10.3 million (21%) have blood pressure in the range 140/90-160/95 mm Hg. An estimated 58000 major CV events per year occur in these patients that would be avoided if their blood pressure was at target levels. If all patients had blood pressure treated to target, the cost to the NHS of managing major CV events would fall by pound 97.2 million per year at 2000/01 prices (95% CI: pound 56- pound 144 million). CONCLUSION: Failure to achieve blood pressure targets contributes substantially to avoidable NHS costs and to the number of CV events in the UK.