Changes in Drug List Prices and Amounts Paid by Patients and Insurers.

Importance: High out-of-pocket drug costs can cause patients to skip treatment and worsen outcomes, and high insurer drug payments could increase premiums. Drug wholesale list prices have doubled in recent years. However, because of manufacturer discounts and rebates, the extent to which increases in wholesale list prices are associated with amounts paid by patients and insurers is poorly characterized. Objective: To determine whether increases in wholesale list prices are associated with increases in amounts paid by patients and insurers for branded medications. Design, Setting, and Participants: Cross-sectional retrospective study analyzing pharmacy claims for patients younger than 65 years in the IBM MarketScan Commercial Database and pricing data from SSR Health, LLC, between January 1, 2010, and December 31, 2016. Pharmacy claims analyzed represent claims of employees and dependents participating in employer health benefit programs belonging to large employers. Rebate data were estimated from sales data from publicly traded companies. Analysis focused on the top 5 patent-protected specialty and 9 traditional brand-name medications with the highest total drug expenditures by commercial insurers nationwide in 2014. Data were analyzed from July 2017 to July 2020. Exposures: Calendar year. Main Outcomes and Measures: Changes in inflation-adjusted amounts paid by patients and insurers for branded medications. Results: In this analysis of 14.4 million pharmacy claims made by 1.8 million patients from 2010-2016, median drug wholesale list price increased by 129% (interquartile range [IQR], 78%-133%), while median insurance payments increased by 64% (IQR, 28%-120%) and out-of-pocket costs increased by 53% (IQR, 42%-82%). The mean percentage of wholesale list price accounted for by discounts increased from 17% in 2010 to 21% in 2016, and the mean percentage of wholesale list price accounted for by rebates increased from 22% in 2010 to 24% in 2016. For specialty medications, median patient out-of-pocket costs increased by 85% (IQR, 73%-88%) from 2010 to 2016 after adjustment for inflation and 42% (IQR, 25%-53%) for nonspecialty medications. During that same period, insurer payments increased by 116% for specialty medications (IQR, 100%-127%) and 28% for nonspecialty medications (IQR, 5%-34%). Conclusions and Relevance: This study's findings suggest that drug list prices more than doubled over a 7-year study period. Despite rising manufacturer discounts and rebates, these price increases were associated with large increases in patient out-of-pocket costs and insurer payments.

Assessment of Platelet REACtivity After Transcatheter Aortic Valve Replacement: The REAC-TAVI Trial.

OBJECTIVES: The REAC-TAVI (Assessment of platelet REACtivity after Transcatheter Aortic Valve Implantation) trial enrolled patients with aortic stenosis (AS) undergoing transcatheter aortic valve replacement (TAVR) pre-treated with aspirin + clopidogrel, aimed to compare the efficacy of clopidogrel and ticagrelor in suppressing high platelet reactivity (HPR) after TAVI. BACKGROUND: Current recommendations support short-term use of aspirin + clopidogrel for patients with severe AS undergoing TAVR despite the lack of compelling evidence. METHODS: This was a prospective, randomized, multicenter investigation. Platelet reactivity was measured at 6 different time points with the VerifyNow assay (Accriva Diagnostics, San Diego, California). HPR was defined as (P2Y12 reaction units (PRU) ≥208. Patients with HPR before TAVR were randomized to either aspirin + ticagrelor or aspirin + clopidogrel for 3 months. Patients without HPR continued with aspirin + clopidogrel (registry cohort). The primary endpoint was non-HPR status (PRU <208) in ≥70% of patients treated with ticagrelor at 90 days post-TAVR. RESULTS: A total of 68 patients were included. Of these, 48 (71%) had HPR (PRU 273 ± 09) and were randomized to aspirin + ticagrelor (n = 24, PRU 277 ± 08) or continued with aspirin + clopidogrel (n = 24, PRU 269 ± 49). The remaining 20 patients (29%) without HPR (PRU 133 ± 12) were included in the registry. Overall, platelet reactivity across all the study time points after TAVR was lower in patients randomized to ticagrelor compared with those treated with clopidogrel, including those enrolled in the registry (p < 0.001). The primary endpoint was achieved in 100% of patients with ticagrelor compared with 21% with clopidogrel (p < 0.001). Interestingly, 33% of clopidogrel responder patients at baseline developed HPR status during the first month after TAVR. CONCLUSIONS: HPR to clopidogrel is present in a considerable number of patients with AS undergoing TAVR. Ticagrelor achieves a better and faster effect, providing sustained suppression of HPR to these patients. (Platelet Reactivity After TAVI: A Multicenter Pilot Study [REAC-TAVI]; NCT02224066).

Comprehensive geriatric assessment and 2-year mortality in elderly patients hospitalized for heart failure.

BACKGROUND: In older adults hospitalized for heart failure, a poor score on a comprehensive geriatric assessment (CGA) is associated with worse prognosis during hospitalization and at 1 month after discharge. However, the association between the CGA score and long-term mortality is uncertain. METHODS AND RESULTS: This is a prospective study of 487 patients aged ≥75 years admitted for decompensated heart failure. At discharge, a CGA score (range, 0-10) was calculated based on limitation in activities of daily living, mobility limitation, comorbidity, cognitive decline, and previous medication use. The analysis of the association between the CGA score and 2-year subsequent mortality was performed with Cox regression and adjusted for the main confounders. A 1-point increase in the CGA score was associated with a 19% higher mortality (hazard ratio, 1.19; 95% confidence interval, 1.11-1.27). Results were similar regardless of age, sex, left ventricular ejection fraction, and the coexistence of atrial fibrillation, ischemic heart disease, or hypertensive cardiopathy. All components of the CGA score showed a consistent association with higher death risk: the hazard ratio (95% confidence interval) of mortality was 1.78 (1.25-2.54) with ≥3 versus 0 limitations in activities of daily living, 1.36 (1.0-1.86) with moderate or severe versus no or mild limitation in mobility, 1.98 (1.29-3.03) with a ≥5 versus ≤1 score on the Charlson index, 2.48 (1.84-3.34) with previous cognitive decline, and 1.77 (0.99-3.18) in those using ≥8 versus ≤3 medications. CONCLUSIONS: The score on a simple CGA is associated with long-term mortality in older patients hospitalized for heart failure.

Comprehensive geriatric assessment and hospital mortality among older adults with decompensated heart failure.

BACKGROUND: The aim of this study is to assess whether a simple comprehensive geriatric assessment (CGA) score predicts hospital mortality among very elderly patients admitted with heart failure (HF). METHODS: This is a prospective follow-up of 581 individuals aged ≥75 years admitted for decompensated HF to an acute geriatric unit from October 2006 to September 2009. A CGA score (range, 0-10) was constructed using baseline individual data on 5 domains: dependence in activities of daily living (Katz index), mobility (qualitative mobility scale), cognition (Mini-Mental State Examination), comorbidity (Charlson index), and number of prescribed medications. RESULTS: Mean age of patients was 85.8 ± 5.8 years, 67% were women, and 75% had preserved ventricular function (ejection fraction >45%). Fifty percent of patients required assistance in ≥1 activities of daily living, 66% had mobility problems, 45% had cognitive impairment, the mean Charlson index was 3.97 ± 3.01, and 36% had >7 medications prescribed. As a result, the mean CGA score was 4.8 ± 2.2. Hospital mortality was 8.2%. In multivariate analysis, variables associated with hospital mortality included New York Heart Association functional class III (odds ratio [OR] 4.1, 95% CI 1.5-10.8), class IV (OR 19.6, 95% CI 6.3-61), pulmonary edema on chest radiography (OR 3.0, 95% CI 1.3-6.6), renal failure (OR 2.8, 95% 1.2-6.2), and the CGA score (OR 1.2, 95% CI 1.02-1.4 for each point of increment). The area under the receiver operating characteristic curve was 0.856 (95% CI 0.790-0.921), and the model classified 93.4% of cases correctly. CONCLUSIONS: In our cohort of very old patients with HF, a simple CGA score predicts hospital mortality.