Prescribing trends of SGLT2 inhibitors among HFrEF and HFpEF patients with and without T2DM, 2013-2021.

BACKGROUND: Sodium-glucose cotransporter-2 inhibitors (SGLT2i) are recommended for treatment of heart failure (HF), regardless of type 2 diabetes (T2DM) status. However, limited data exist on SGLT2i prescribing in HF patients without T2DM or across HF subtypes. METHODS: This was a serial, cross-sectional study of US MarketScan commercial and Medicare claims (2013-2021). Prevalence of SGLT2i was calculated by calendar year among HFrEF and HFpEF patients and stratified by T2DM status. RESULTS: Among 218,066 HFrEF patients [mean (SD): 54.9 (8.92) years; 66.4% male], the prevalence of SGLT2i use increased from 0.3 to 18.6%, while among 150,437 HFpEF patients [56.5 (7.77) years; 47.6% male], it rose from 0.5 to 9.9%. These increases were driven by the subgroup with comorbid T2DM. SGLT2i prevalence use ratios among patients with T2DM compared to those without decreased from > 100 in 2018 to 3.8 in 2021 among HFrEF patients, and from 83.1 in 2018 to 17.5 in 2021, coinciding with the publication of landmark trials and corresponding changes in clinical guidelines. CONCLUSIONS: SGLT2i use rose rapidly following changes in guidelines but remained low among those without T2DM. By the end of the study, approximately 1 in 3 HFrEF and 1 in 5 HFpEF patients with T2DM were using an SGLT2i, compared to only 1 in 11 HFrEF and 1 in 85 HFpEF patients without T2DM. Future work identifying barriers with the uptake of GDMT, including SGLT2i, among HF patients is needed.

Prospective Real-Time Validation of a Lung Ultrasound Deep Learning Model in the ICU.

OBJECTIVES: To evaluate the accuracy of a bedside, real-time deployment of a deep learning (DL) model capable of distinguishing between normal (A line pattern) and abnormal (B line pattern) lung parenchyma on lung ultrasound (LUS) in critically ill patients. DESIGN: Prospective, observational study evaluating the performance of a previously trained LUS DL model. Enrolled patients received a LUS examination with simultaneous DL model predictions using a portable device. Clip-level model predictions were analyzed and compared with blinded expert review for A versus B line pattern. Four prediction thresholding approaches were applied to maximize model sensitivity and specificity at bedside. SETTING: Academic ICU. PATIENTS: One-hundred critically ill patients admitted to ICU, receiving oxygen therapy, and eligible for respiratory imaging were included. Patients who were unstable or could not undergo an LUS examination were excluded. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: A total of 100 unique ICU patients (400 clips) were enrolled from two tertiary-care sites. Fifty-six patients were mechanically ventilated. When compared with gold standard expert annotation, the real-time inference yielded an accuracy of 95%, sensitivity of 93%, and specificity of 96% for identification of the B line pattern. Varying prediction thresholds showed that real-time modification of sensitivity and specificity according to clinical priorities is possible. CONCLUSIONS: A previously validated DL classification model performs equally well in real-time at the bedside when platformed on a portable device. As the first study to test the feasibility and performance of a DL classification model for LUS in a dedicated ICU environment, our results justify further inquiry into the impact of employing real-time automation of medical imaging into the care of the critically ill.

Cardiovascular outcomes with SGLT2 inhibitors versus DPP4 inhibitors and GLP-1 receptor agonists in patients with heart failure with reduced and preserved ejection fraction.

BACKGROUND: No study has compared the cardiovascular outcomes for sodium-glucose cotransporter-2 inhibitors (SGLT2i) head-to-head against other glucose-lowering therapies, including dipeptidyl peptidase 4 inhibitor (DDP4i) or glucagon-like peptide-1 receptor agonist (GLP-1RA)-which also have cardiovascular benefits-in patients with heart failure with reduced (HFrEF) or preserved (HFpEF) ejection fraction. METHODS: Medicare fee-for-service data (2013-2019) were used to create four pair-wise comparison cohorts of type 2 diabetes patients with: (1a) HFrEF initiating SGLT2i versus DPP4i; (1b) HFrEF initiating SGLT2i versus GLP-1RA; (2a) HFpEF initiating SGLT2i versus DPP4i; and (2b) HFpEF initiating SGLT2i versus GLP-1RA. The primary outcomes were (1) hospitalization for heart failure (HHF) and (2) myocardial infarction (MI) or stroke hospitalizations. Adjusted hazards ratios (HR) and 95% CIs were estimated using inverse probability of treatment weighting. RESULTS: Among HFrEF patients, initiation of SGLT2i versus DPP4i (cohort 1a; n = 13,882) was associated with a lower risk of HHF (adjusted Hazard Ratio [HR (95% confidence interval)], 0.67 (0.63, 0.72) and MI or stroke (HR: 0.86 [0.75, 0.99]), and initiation of SGLT2i versus GLP-1RA (cohort 1b; n = 6951) was associated with lower risk of HHF (HR: 0.86 [0.79, 0.93]), but not MI or stroke (HR: 1.02 [0.85, 1.22]). Among HFpEF patients, initiation of SGLT2i versus DPP4i (cohort 2a; n = 17,493) was associated with lower risk of HHF (HR: 0.65 [0.61, 0.69]) but not MI or stroke (HR: 0.90 [0.79, 1.02]), and initiation of SGLT2i versus GLP-1RA (cohort 2b; n = 9053) was associated with lower risk of HHF (0.89 [0.83, 0.96]), but not MI or stroke (HR: 0.97 [0.83, 1.14]). Results were robust across range of secondary outcomes (e.g., all-cause mortality) and sensitivity analyses. CONCLUSIONS: Bias from residual confounding cannot be ruled out. Use of SGLT2i was associated with reduced risk of HHF against DPP4i and GLP-1RA, reduced risk of MI or stroke against DPP4i within the HFrEF subgroup, and comparable risk of MI or stroke against GLP-1RA. Notably, the magnitude of cardiovascular benefit conferred by SGLT2i was similar among patients with HFrEF and HFpEF.

Improving the prospective prediction of a near-term suicide attempt in veterans at risk for suicide, using a go/no-go task.

BACKGROUND: Neurocognitive testing may advance the goal of predicting near-term suicide risk. The current study examined whether performance on a Go/No-go (GNG) task, and computational modeling to extract latent cognitive variables, could enhance prediction of suicide attempts within next 90 days, among individuals at high-risk for suicide. METHOD: 136 Veterans at high-risk for suicide previously completed a computer-based GNG task requiring rapid responding (Go) to target stimuli, while withholding responses (No-go) to infrequent foil stimuli; behavioral variables included false alarms to foils (failure to inhibit) and missed responses to targets. We conducted a secondary analysis of these data, with outcomes defined as actual suicide attempt (ASA), other suicide-related event (OtherSE) such as interrupted/aborted attempt or preparatory behavior, or neither (noSE), within 90-days after GNG testing, to examine whether GNG variables could improve ASA prediction over standard clinical variables. A computational model (linear ballistic accumulator, LBA) was also applied, to elucidate cognitive mechanisms underlying group differences. RESULTS: On GNG, increased miss rate selectively predicted ASA, while increased false alarm rate predicted OtherSE (without ASA) within the 90-day follow-up window. In LBA modeling, ASA (but not OtherSE) was associated with decreases in decisional efficiency to targets, suggesting differences in the evidence accumulation process were specifically associated with upcoming ASA. CONCLUSIONS: These findings suggest that GNG may improve prediction of near-term suicide risk, with distinct behavioral patterns in those who will attempt suicide within the next 90 days. Computational modeling suggests qualitative differences in cognition in individuals at near-term risk of suicide attempt.

Risks for Anaphylaxis With Intravenous Iron Formulations : A Retrospective Cohort Study.

BACKGROUND: The risks for anaphylaxis among intravenous (IV) iron products currently in use have not been assessed. OBJECTIVE: To compare risks for anaphylaxis among 5 IV iron products that are used frequently. DESIGN: Retrospective cohort study using a target trial emulation framework. SETTING: Medicare fee-for-service data with Part D coverage between July 2013 and December 2018. PARTICIPANTS: Older adults receiving their first administration of IV iron. MEASUREMENTS: The primary outcome was the occurrence of anaphylaxis within 1 day of IV iron administration, ascertained using a validated case definition. Analysis was adjusted for 40 baseline covariates using inverse probability of treatment weighting. The adjusted incidence rates (IRs) for anaphylaxis per 10 000 first administrations and odds ratios (ORs) were computed. RESULTS: The adjusted IRs for anaphylaxis per 10 000 first administrations were 9.8 cases (95% CI, 6.2 to 15.3 cases) for iron dextran, 4.0 cases (CI, 2.5 to 6.6 cases) for ferumoxytol, 1.5 cases (CI, 0.3 to 6.6 cases) for ferric gluconate, 1.2 cases (CI, 0.6 to 2.5 cases) for iron sucrose, and 0.8 cases (CI, 0.3 to 2.6 cases) for ferric carboxymaltose. Using iron sucrose as the referent category, the adjusted ORs for anaphylaxis were 8.3 (CI, 3.5 to 19.8) for iron dextran and 3.4 (CI, 1.4 to 8.3) for ferumoxytol. When cohort entry was restricted to the period after withdrawal of high-molecular-weight iron dextran from the U.S. market in 2014, the risk for anaphylaxis associated with low-molecular-weight iron dextran (OR, 8.4 [CI, 2.8 to 24.7]) did not change appreciably. Anaphylactic reactions requiring hospitalizations were observed only among patients using iron dextran or ferumoxytol. LIMITATION: Generalizability to non-Medicare populations. CONCLUSION: The rates of anaphylaxis were very low with all IV iron products but were 3- to 8-fold greater for iron dextran and ferumoxytol than for iron sucrose. PRIMARY FUNDING SOURCE: None.

Risk of Cardiovascular Outcomes in Patients With Type 2 Diabetes After Addition of SGLT2 Inhibitors Versus Sulfonylureas to Baseline GLP-1RA Therapy.

BACKGROUND: Several glucagon-like peptide receptor agonists (GLP-1RA) and sodium-glucose cotransporter-2 inhibitors (SGLT2i) have demonstrated cardiovascular benefit in type 2 diabetes in large randomized controlled trials in patients with established cardiovascular disease or multiple risk factors. However, few trial participants were on both agents, and it remains unknown whether the addition of SGLT2i to GLP-1RA therapy has further cardiovascular benefits. METHODS: Patients adding either SGLT2i or sulfonylureas to baseline GLP-1RA were identified within 3 US claims datasets (2013-2018) and were 1:1 propensity score-matched, adjusting for >95 baseline covariates. The primary outcomes were a composite cardiovascular end point (comprising myocardial infarction, stroke, and all-cause mortality) and heart failure hospitalization. Adjusted hazard ratios (HRs) and 95% CIs were estimated in each dataset and pooled through fixed-effects meta-analysis. RESULTS: Among 12 584 propensity score-matched pairs (mean [SD] age, 58.3 [10.9] years; 48.2% male) across the 3 datasets, there were 107 composite cardiovascular end point events (incidence rate per 1000 person-years, 9.9 [95% CI, 8.1-11.9]) among SGLT2i initiators compared with 129 events (incidence rate, 13.0 [95% CI, 10.9-15.3]) among sulfonylurea initiators, corresponding to an adjusted pooled HR of 0.76 (95% CI, 0.59-0.98); this decrease in composite cardiovascular end point was driven by numeric decreases in the risk of myocardial infarction (HR, 0.71 [95% CI, 0.51-1.003]) and all-cause mortality (HR, 0.68 [95% CI, 0.40-1.14]) but not stroke (HR, 1.05 [95% CI, 0.62-1.79]). For the outcome of heart failure hospitalization, there were 141 events (incidence rate, 13.0 [95% CI, 11.0-15.2]) among SGLT2i initiators versus 206 events (incidence rate, 20.8 [95% CI, 18.1-23.8]) among sulfonylurea initiators, corresponding to an adjusted pooled HR of 0.65 (95% CI, 0.50-0.82). CONCLUSIONS: Risk of residual confounding cannot be fully excluded. Individual therapeutic agents within each class may have different magnitudes of effect. In this large real-world cohort of patients with diabetes already on GLP-1RA, addition of SGLT2i conferred greater cardiovascular benefit compared with addition of sulfonylurea. The magnitude of the cardiovascular risk reduction was comparable with the benefit seen in cardiovascular outcome trials of SGLT2i versus placebo, where baseline GLP-1RA use was minimal.

Risk of clinically relevant hyperglycemia with metoprolol compared to carvedilol in older adults with heart failure and diabetes.

BACKGROUND: Although prior literature suggests that metoprolol may worsen glucose control compared to carvedilol, whether this has clinical relevance among older adults with diabetes and heart failure (HF) remains an open question. METHODS: This was a US retrospective cohort study utilizing data sourced from a 50% national sample of Medicare fee-for-service claims of patients with part D prescription drug coverage (2007-2017). Among patients with diabetes and HF, we identified initiators of metoprolol or carvedilol, which were 1:1 propensity score matched on >90 variables. The primary outcome was initiation of a new oral or injectable antidiabetic medication (proxy for uncontrolled diabetes); secondary outcomes included initiation of insulin and severe hyperglycemic event (composite of emergency room visits or hospitalizations related to hyperglycemia). RESULTS: Among 24 239 propensity score-matched pairs (mean [SD] age 77.7 [8.0] years; male [39.1%]), there were 8150 (incidence rate per 100 person-years [IR] = 33.5) episodes of antidiabetic medication initiation among metoprolol users (exposure arm) compared to 8576 (IR = 33.4) among carvedilol users (comparator arm) compared to corresponding to an adjusted hazard ratio (aHR) of 0.97 (95% confidence interval [CI]: 0.94, 1.01). Similarly, metoprolol was not associated with a significant increase in the risk of secondary outcomes including insulin initiation: aHR of 0.98 (95% CI: 0.93, 1.04) and severe hyperglycemic events: aHR of 0.98 (95% CI: 0.93, 1.02). CONCLUSIONS: In this large study of older adults with HF and diabetes, initiation of metoprolol compared to carvedilol was not associated with an increase in the risk of clinically relevant hyperglycemia.

Dynamic Assessment of Fluid Responsiveness in Surgical ICU Patients Through Stroke Volume Variation is Associated With Decreased Length of Stay and Costs: A Systematic Review and Meta-Analysis.

Static indices, such as the central venous pressure, have proven to be inaccurate predictors of fluid responsiveness. An emerging approach uses dynamic assessment of fluid responsiveness (FT-DYN), such as stroke volume variation (SVV) or surrogate dynamic variables, as more accurate measures of volume status. Recent work has demonstrated that goal-directed therapy guided by FT-DYN was associated with reduced intensive care unit (ICU) mortality; however, no study has specifically assessed this in surgical ICU patients. This study aimed to conduct a systematic review and meta-analysis on the impact of employing FT-DYN in the perioperative care of surgical ICU patients on length of stay in the ICU. As secondary objectives, we performed a cost analysis of FT-DYN and assessed the impact of FT-DYN versus standard care on hospital length of stay and mortality. We identified all randomized controlled trials (RCTs) through MEDLINE, EMBASE, and CENTRAL that examined adult patients in the ICU who were randomized to standard care or to FT-DYN from inception to September 2017. Two investigators independently reviewed search results, identified appropriate studies, and extracted data using standardized spreadsheets. A random effect meta-analysis was carried out. Eleven RCTs were included with a total of 1015 patients. The incorporation of FT-DYN through SVV in surgical patients led to shorter ICU length of stay (weighted mean difference [WMD], -1.43d; 95% confidence interval [CI], -2.09 to -0.78), shorter hospital length of stay (WMD, -1.96d; 95% CI, -2.34 to -1.59), and trended toward improved mortality (odds ratio, 0.55; 95% CI, 0.30-1.03). There was a decrease in daily ICU-related costs per patient for those who received FT-DYN in the perioperative period (WMD, US$ -1619; 95% CI, -2173.68 to -1063.26). Incorporation of FT-DYN through SVV in the perioperative care of surgical ICU patients is associated with decreased ICU length of stay, hospital length of stay, and ICU costs.

Sodium-Glucose Cotransporter-2 Inhibitors and the Risk for Severe Urinary Tract Infections: A Population-Based Cohort Study.

Background: Prior studies evaluating risk for severe urinary tract infections (UTIs) with sodium-glucose cotransporter-2 (SGLT-2) inhibitors have reported conflicting findings. Objective: To assess whether patients initiating use of SGLT-2 inhibitors were at increased risk for severe UTI events compared with those initiating use of dipeptidyl peptidase-4 (DPP-4) inhibitors or glucagon-like peptide-1 receptor (GLP-1) agonists. Design: Population-based cohort study. Setting: 2 large, U.S.-based databases of commercial claims (March 2013 to September 2015). Participants: Within each database, 2 cohorts were created and matched 1:1 on propensity score. Patients were aged 18 years or older, had type 2 diabetes mellitus, and were initiating use of SGLT-2 inhibitors versus DPP-4 inhibitors (cohort 1) or GLP-1 agonists (cohort 2). Measurements: The primary outcome was a severe UTI event, defined as a hospitalization for primary UTI, sepsis with UTI, or pyelonephritis; the secondary outcome was outpatient UTI treated with antibiotics. Hazard ratios (HRs) were estimated in each propensity score-matched cohort, with adjustment for more than 90 baseline characteristics. Results: After 1:1 matching on propensity score, 123 752 patients were identified in cohort 1 and 111 978 in cohort 2 in the 2 databases. In cohort 1, persons newly receiving SGLT-2 inhibitors had 61 severe UTI events (incidence rate [IR] per 1000 person-years, 1.76), compared with 57 events in the DPP-4 inhibitor group (IR, 1.77) (HR, 0.98 [95% CI, 0.68 to 1.41]). In cohort 2, those receiving SGLT-2 inhibitors had 73 events (IR, 2.15), compared with 87 events in the GLP-1 agonist group (IR, 2.96) (HR, 0.72 [CI, 0.53 to 0.99]). Findings were robust across sensitivity analyses; within several subgroups of age, sex, and frailty; and for canagliflozin and dapagliflozin individually. In addition, SGLT-2 inhibitors were not associated with increased risk for outpatient UTIs (cohort 1: HR, 0.96 [CI, 0.89 to 1.04]; cohort 2: HR, 0.91 [CI, 0.84 to 0.99]). Limitation: Generalizability of the study findings may be limited to patients with commercial insurance. Conclusion: In a large cohort of patients seen in routine clinical practice, risk for severe and nonsevere UTI events among those initiating SGLT-2 inhibitor therapy was similar to that among patients initiating treatment with other second-line antidiabetic medications. Primary Funding Source: Brigham and Women's Hospital, Division of Pharmacoepidemiology and Pharmacoeconomics.

Frailty and Associated Outcomes and Resource Utilization Among Older ICU Patients With Suspected Infection.

OBJECTIVES: Suspected infection and sepsis are common conditions seen among older ICU patients. Frailty has prognostic importance among critically ill patients, but its impact on outcomes and resource utilization in older patients with suspected infection is unknown. We sought to evaluate the association between patient frailty (defined as a Clinical Frailty Scale ≥ 5) and outcomes of critically ill patients with suspected infection. We also evaluated the association between frailty and the quick Sequential Organ Failure Assessment score. DESIGN: Analysis of a prospectively collected registry. SETTING: Two hospitals within a single tertiary care level hospital system between 2011 and 2016. PATIENTS: We analyzed 1,510 patients 65 years old or older (at the time of ICU admission) and with suspected infection at the time of ICU admission. Of these, 507 (33.6%) were categorized as "frail" (Clinical Frailty Scale ≥ 5). INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The primary outcome was in-hospital mortality. A total of 558 patients (37.0%) died in-hospital. Frailty was associated with increased risk of in-hospital death (adjusted odds ratio, 1.81 [95% CIs, 1.34-2.49]). Frailty was also associated with higher likelihood of discharge to long-term care (adjusted odds ratio, 2.06 [95% CI, 1.50-2.64]) and higher likelihood of readmission within 30 days (adjusted odds ratio, 1.83 [95% CI, 1.38-2.34]). Frail patients had increased ICU resource utilization and total costs. The combination of frailty and quick Sequential Organ Failure Assessment greater than or equal to 2 further increased the risk of death (adjusted odds ratio, 7.54 [95% CI, 5.82-9.90]). CONCLUSIONS: The presence of frailty among older ICU patients with suspected infection is associated with increased mortality, discharge to long-term care, hospital readmission, resource utilization, and costs. This work highlights the importance of clinical frailty in risk stratification of older ICU patients with suspected infection.

Comparative risk of genital infections associated with sodium-glucose co-transporter-2 inhibitors.

The extent to which sodium-glucose co-transporter-2 (SGLT2) inhibitors increase the risk of genital infections in routine clinical care, compared with other antidiabetic medications, is not clear, or whether the increased risk is consistent across gender or age subgroups, within individual SGLT2 agents, or if it is more pronounced at a particular time after treatment initiation. We conducted a retrospective cohort study using two US commercial claims databases (2013-2017). In the primary analysis, 1:1 propensity score-matched cohorts of female and male subjects with type 2 diabetes mellitus initiating SGLT2 versus dipeptidyl peptidase-4 inhibitors were created. The outcome was a composite of genital candidal infections, vaginitis or vulvovaginitis in women, and genital candidal infections, balanitis, balanoposthitis, phimosis or paraphimosis in men. Among propensity score-matched cohorts of 129 994 women and 156 074 men, the adjusted hazard ratio (HR) and excess risk per 1000 person-years for SGLT2 versus DPP-4 inhibitors was 2.81 (95% confidence interval [CI], 2.64, 2.99) and 87.4 (95% CI, 79.1, 96.2) respectively for women, and was 2.68 (95% CI, 2.31, 3.11) and 11.9 (95% CI, 9.3-15.0) for men. Findings were similar in the SGLT2 inhibitor versus GLP-1 agonist comparison, more pronounced in the subgroup of patients aged ≥60 (HR, 4.45 [95% CI, 3.83-5.17] in women and 3.30 [95% CI, 2.56-4.25] in men), and no meaningful difference across individual SGLT2 inhibitors was identified. This increase in risk was evident in the first month of treatment initiation and remained elevated throughout the course of therapy. SGLT2 inhibitors were associated with an approximately 3-fold increase in risk of genital infections.

Predictors of Drug Shortages and Association with Generic Drug Prices: A Retrospective Cohort Study.

BACKGROUND: Prescription drug shortages can disrupt essential patient care and drive up drug prices. OBJECTIVE: To evaluate some predictors of shortages within a large cohort of generic drugs in the United States and to determine the association between drug shortages and changes in generic drug prices. METHODS: This was a retrospective cohort study. Outpatient prescription claims from commercial health plans between 2008 and 2014 were analyzed. Seven years of data were divided into fourteen 6-month periods; the first period was designated as the baseline period. The first model estimated the probability of experiencing a drug shortage using drug-specific competition levels, market sizes, formulations (e.g., capsules), and drug prices as predictors. The second model estimated the percentage change in drug prices from baseline on the basis of drug shortage duration. RESULTS: From 1.3 billion prescription claims, a cohort of 1114 generic drugs was identified. Low-priced generic drugs were at a higher risk for drug shortages compared with medium- and high-priced generic drugs, with odds ratios of 0.60 (95% confidence interval [CI] 0.44-0.82) and 0.72 (95% CI 0.52-0.99), respectively. Compared with periods of no shortage, drug shortages lasting less than 6 months, 6 to 12 months, 12 to 18 months, and at least 18 months had corresponding price increases of 6.0% (95% CI 4.7-7.4), 10.9% (95% CI 8.5-13.4), 14.2% (95% CI 10.6-17.9), and 14.0% (95% CI 9.1-19.2), respectively. CONCLUSIONS: Study findings may not be generalizable to drugs that became generic after 2008 or those commonly used in an inpatient setting. The lowest priced drugs are at a substantially elevated risk of experiencing a drug shortage. Periods of drug shortages were associated with modest increases in drug prices.

High Generic Drug Prices and Market Competition: A Retrospective Cohort Study.

BACKGROUND: Prices for some generic drugs have increased in recent years, adversely affecting patients who rely on them. OBJECTIVE: To determine the association between market competition levels and the change in generic drug prices in the United States. DESIGN: Retrospective cohort study. SETTING: Prescription claims from commercial health plans between 2008 and 2013. MEASUREMENTS: The 5.5 years of data were divided into 11 study periods of 6 months each. The Herfindahl-Hirschman Index (HHI)-calculated by summing the squares of individual manufacturers' market shares, with higher values indicating a less competitive market-and average drug prices were estimated for the generic drugs in each period. The HHI value estimated in the baseline period (first half of 2008) was modeled as a fixed covariate. Models estimated price changes over time by level of competition, adjusting for drug shortages, market size, and dosage forms. RESULTS: From 1.08 billion prescription claims, a cohort of 1120 generic drugs was identified. After adjustment, drugs with quadropoly (HHI value of 2500, indicating relatively high levels of competition), duopoly (HHI value of 5000), near-monopoly (HHI value of 8000), and monopoly (HHI value of 10 000) levels of baseline competition were associated with price changes of -31.7% (95% CI, -34.4% to -28.9%), -11.8% (CI, -18.6% to -4.4%), 20.1% (CI, 5.5% to 36.6%), and 47.4% (CI, 25.4% to 73.2%), respectively, over the study period. LIMITATION: Study findings may not be generalizable to drugs that became generic after 2008. CONCLUSION: Market competition levels were associated with a change in generic drug prices. Such measurements may be helpful in identifying older prescription drugs at higher risk for price change in the future. PRIMARY FUNDING SOURCE: None.

Initiation patterns of anticoagulants for atrial fibrillation among older UK adults with and without chronic kidney disease, 2010-2020.

BACKGROUND: There is a paucity of data on the initiation patterns of anticoagulants among older atrial fibrillation patients with and without chronic kidney disease (CKD). SETTING AND METHODS: We used the UK Clinical Practice Research Datalink (2010-2020) to conduct a retrospective cohort study to evaluate anticoagulant initiation patterns for older adults (≥65 years) with CKD (N=18 421) and without CKD (N=41 901), categorised by severity of CKD: stages 3a, 3b and 4, and initiation dose by respective direct oral anticoagulant (DOAC). RESULTS: Over the study period, warfarin initiations sharply declined and were replaced by DOACs regardless of CKD status or stage. By 2020, patients with CKD were modestly more likely (8.8% difference) to initiate apixaban compared with those without CKD (58.8% vs 50.0%; p<0.01). Among patients with CKD, those with stages 3a and 3b CKD had higher apixaban initiations compared with stage 4 CKD (56.9% and 64.6% vs 52.9%, respectively; p<0.01). Conversely, patients with stage 4 CKD were over three times more likely to initiate warfarin (14.7%) compared with those with stage 3a (2.6%) and 3b (4.0%) CKD (p<0.01). Throughout the study period, there was a rise in the proportion of patients initiating the higher 10 mg daily dose for apixaban, with an increase of 20.6% (from 64.3% in 2013 to 84.9% in 2020; p value for trend <0.01) among patients without CKD, and 21.8% (53.1% to 74.9%; p<0.01), 24.4% (18.8% to 43.2%; p<0.01) and 18.5% (0.0% to 18.2%; p<0.01) among patients with stages 3a, 3b and 4 CKD, respectively. CONCLUSIONS AND RELEVANCE: Initiation of DOACs increased regardless of CKD status and stage, although with a reduced magnitude in severe CKD. Apixaban emerged as the preferred agent, with a secular trend towards the higher initiation dose in all subgroups. These findings illuminate evolving trends and priorities in anticoagulant preferences among patients with and without CKD.

Racial and Ethnic Disparities in Initiation of Direct Oral Anticoagulants Among Medicare Beneficiaries.

Importance: The influence of race and ethnicity on initiation of direct oral anticoagulants (DOACs) is relatively understudied in Medicare data. Objective: To investigate disparities in the initiation of DOACs compared with warfarin by race, ethnicity, and social vulnerability. Design, Setting, and Participants: This retrospective cohort study used a 50% sample of Medicare fee-for-service data from January 1, 2010, to December 31, 2019 (mean patient enrollment duration, 7.7 years). Analysis took place between January 2023 and February 2024. A cohort of older adults (aged ≥65 years) with atrial fibrillation who newly initiated warfarin or DOACs (dabigatran, rivaroxaban, apixaban, and edoxaban) was identified. Exposure: Patients were classified as non-Hispanic White, non-Hispanic Black, and Hispanic. Main Outcomes and Measures: The likelihood of starting use of DOACs compared with warfarin was modeled, adjusting for race, ethnicity, age, sex, county-level social vulnerability, and other clinical factors. Results: Among 950 698 anticoagulation initiations, consisting of 680 974 DOAC users and 269 724 warfarin users (mean [SD] age, 78.5 [7.6] years; 52.6% female), 5.2% were Black, 4.3% were Hispanic, and 86.7% were White. During the 10-year study period, DOAC use increased for all demographic groups. After adjustment, compared with White patients, Black patients were 23% less likely (adjusted odds ratio [AOR, 0.77; 95% CI, 0.75-0.79) and Hispanic patients were 13% less likely (AOR, 0.87; 95% CI, 0.85-0.89) to initiate DOAC use. Disparities in DOAC initiation were greatest among Black patients in the earlier years but attenuated during the study period. For instance, in 2010, the OR of Black patients initiating DOACs was 0.54 (95% CI, 0.50-0.57), attenuating linearly over time to 0.69 by 2013 (95% CI, 0.65-0.74) and 0.83 (95% CI, 0.78-0.89) by 2017. By 2019, these differences became nonsignificant (OR, 1.08; 95% CI, 0.99-1.18). Conclusions and Relevance: In this cohort study of Medicare patients with atrial fibrillation, Black and Hispanic patients were less likely to initiate DOACs for atrial fibrillation, although these differences diminished over time. Identifying the factors behind these early disparities is crucial for ensuring equitable access to novel therapies as they emerge for Black and Hispanic populations.