Effectiveness and safety of prophylactic anticoagulation among hospitalized patients with inflammatory bowel disease.

ABSTRACT: Hospitalized patients with inflammatory bowel disease (IBD) are at increased risk of venous thromboembolism (VTE). We aimed to evaluate the effectiveness and safety of prophylactic anticoagulation compared with no anticoagulation in hospitalized patients with IBD. We conducted a retrospective cohort study using a hospital-based database. We included patients with IBD who had a length of hospital stay ≥2 days between 1 January 2016 and 31 December 2019. We excluded patients who had other indications for anticoagulation, users of direct oral anticoagulants, warfarin, therapeutic-intensity heparin, and patients admitted for surgery. We defined exposure to prophylactic anticoagulation using charge codes. The primary effectiveness outcome was VTE. The primary safety outcome was bleeding. We used propensity score matching to reduce potential differences between users and nonusers of anticoagulants and Cox proportional-hazards regression to estimate adjusted hazard ratios (HRs) and 95% confidence intervals (CIs). The analysis included 56 194 matched patients with IBD (users of anticoagulants, n = 28 097; nonusers, n = 28 097). In the matched sample, prophylactic use of anticoagulants (vs no use) was associated with a lower rate of VTE (HR, 0.62; 95% CI, 0.41-0.94) and with no difference in the rate of bleeding (HR, 1.05; 95% CI, 0.87-1.26). In this study of hospitalized patients with IBD, prophylactic use of heparin was associated with a lower rate of VTE without increasing bleeding risk compared with no anticoagulation. Our results suggest potential benefits of prophylactic anticoagulation to reduce the burden of VTE in hospitalized patients with IBD.

Incidence, Prevalence, and Racial and Ethnic Distribution of Inflammatory Bowel Disease in the United States.

BACKGROUND & AIMS: We sought to estimate the incidence, prevalence, and racial-ethnic distribution of physician-diagnosed inflammatory bowel disease (IBD) in the United States. METHODS: The study used 4 administrative claims data sets: a 20% random sample of national fee-for-service Medicare data (2007 to 2017); Medicaid data from Florida, New York, Pennsylvania, Ohio, and California (1999 to 2012); and commercial health insurance data from Anthem beneficiaries (2006 to 2018) and Optum's deidentified Clinformatics Data Mart (2000 to 2017). We used validated combinations of medical diagnoses, diagnostic procedures, and prescription medications to identify incident and prevalent diagnoses. We computed pooled age-, sex-, and race/ethnicity-specific insurance-weighted estimates and pooled estimates standardized to 2018 United States Census estimates with 95% confidence intervals (CIs). RESULTS: The age- and sex-standardized incidence of IBD per 100,000 person-years was 10.9 (95% CI, 10.6-11.2). The incidence of IBD peaked in the third decade of life, decreased to a relatively stable level across the fourth to eighth decades, and declined further. The age-, sex- and insurance-standardized prevalence of IBD was 721 per 100,000 population (95% CI, 717-726). Extrapolated to the 2020 United States Census, an estimated 2.39 million Americans are diagnosed with IBD. The prevalence of IBD per 100,000 population was 812 (95% CI, 802-823) in White, 504 (95% CI, 482-526) in Black, 403 (95% CI, 373-433) in Asian, and 458 (95% CI, 440-476) in Hispanic Americans. CONCLUSIONS: IBD is diagnosed in >0.7% of Americans. The incidence peaks in early adulthood and then plateaus at a lower rate. The disease is less commonly diagnosed in Black, Asian, and Hispanic Americans.

Development and Validation of Claims-Based Definitions to Identify Incident and Prevalent Inflammatory Bowel Disease in Administrative Healthcare Databases.

BACKGROUND: To facilitate inflammatory bowel disease (IBD) research in the United States, we developed and validated claims-based definitions to identify incident and prevalent IBD diagnoses using administrative healthcare claims data among multiple payers. METHODS: We used data from Medicare, Medicaid, and the HealthCore Integrated Research Database (Anthem commercial and Medicare Advantage claims). The gold standard for validation was review of medical records. We evaluated 1 incidence and 4 prevalence algorithms based on a combination of International Classification of Diseases codes, National Drug Codes, and Current Procedural Terminology codes. The claims-based incident diagnosis date needed to be within ±90 days of that recorded in the medical record to be valid. RESULTS: We reviewed 111 charts of patients with a potentially incident diagnosis. The positive predictive value (PPV) of the claims algorithm was 91% (95% confidence interval [CI], 81%-97%). We reviewed 332 charts to validate prevalent case definition algorithms. The PPV was 94% (95% CI, 86%-98%) for ≥2 IBD diagnoses and presence of prescriptions for IBD medications, 92% (95% CI, 85%-97%) for ≥2 diagnoses without any medications, 78% (95% CI, 67%-87%) for a single diagnosis and presence of an IBD medication, and 35% (95% CI, 25%-46%) for 1 physician diagnosis and no IBD medications. CONCLUSIONS: Through a combination of diagnosis, procedural, and medication codes in insurance claims data, we were able to identify incident and prevalent IBD cases with high accuracy. These algorithms can be useful for the ascertainment of IBD cases in future studies.

Real-World Evidence Comparing Vedolizumab and Ustekinumab in Antitumor Necrosis Factor-Experienced Patients With Crohn's Disease.

INTRODUCTION: Many patients with Crohn's disease (CD) lose response or become intolerant to antitumor necrosis factor (TNF) therapy and subsequently switch out of class. We compared the effectiveness and safety of ustekinumab to vedolizumab in a large, geographically diverse US population of TNF-experienced patients with CD. METHODS: We conducted a retrospective cohort study using longitudinal claims data from a large US insurer (Anthem, Inc.). We identified patients with CD initiating vedolizumab or ustekinumab with anti-TNF treatment in the prior 6 months. Our primary outcome was treatment persistence for >52 weeks. Secondary outcomes included (i) all-cause hospitalization, (ii) hospitalization for CD with surgery, (iii) hospitalization for CD without surgery, and (iv) hospitalization for infection. Propensity score fine stratification was used to control for demographic and baseline clinical characteristics and prior treatments. RESULTS: Among 885 new users of ustekinumab and 490 new users of vedolizumab, we observed no difference in treatment persistence (adjusted risk ratio 1.09 [95% confidence interval 0.95-1.25]). Ustekinumab was associated with a lower rate of all-cause hospitalization (adjusted hazard ratio 0.73 [0.59-0.91]), nonsurgical CD hospitalization (adjusted hazard ratio 0.58 [0.40-0.83]), and hospitalization for infection (adjusted hazard ratio 0.56 [0.34-0.92]). DISCUSSION: This real-world comparative effectiveness study of anti-TNF-experienced patients with CD initiating vedolizumab or ustekinumab showed similar treatment persistence rates beyond 52 weeks, although secondary outcomes such as all-cause hospitalizations, nonsurgical CD hospitalizations, and hospitalizations for infection favored ustekinumab initiation. We, therefore, advocate for individualized decision making in this medically refractory population, considering patient preference and other factors such as cost and route of administration.

Apixaban Versus Rivaroxaban in Patients With Atrial Fibrillation and Valvular Heart Disease : A Population-Based Study.

BACKGROUND: Although apixaban and rivaroxaban are commonly used in patients with atrial fibrillation (AF) and valvular heart disease (VHD), there is limited evidence comparing the 2 drugs in these patients. OBJECTIVE: To emulate a target trial of effectiveness and safety of apixaban and rivaroxaban in patients with AF and VHD. DESIGN: New-user, active comparator, cohort study design. SETTING: Commercial health insurance database from 1 January 2013 to 31 December 2020. PATIENTS: New users of apixaban or rivaroxaban who had a diagnosis of AF and VHD before initiation of anticoagulant therapy. MEASUREMENTS: The primary effectiveness outcome was a composite of ischemic stroke or systemic embolism. The primary safety outcome was a composite of gastrointestinal or intracranial bleeding. Cox proportional hazards regression with a robust variance estimator was used to estimate hazard ratios (HRs) and 95% CIs. RESULTS: When compared with rivaroxaban in a propensity score-matched cohort of 19 894 patients (9947 receiving each drug), apixaban was associated with a lower rate of ischemic stroke or systemic embolism (HR, 0.57 [95% CI, 0.40 to 0.80]) and bleeding (HR, 0.51 [CI, 0.41 to 0.62]). The absolute reduction in the probability of stroke or systemic embolism with apixaban compared with rivaroxaban was 0.0026 within 6 months and 0.011 within 1 year of treatment initiation. The absolute reduction in the probability of bleeding events with apixaban compared with rivaroxaban was 0.012 within 6 months and 0.019 within 1 year of treatment initiation. LIMITATION: Short follow-up time and inability to ascertain some types of VHD. CONCLUSION: In this study of patients with AF and VHD, patients receiving apixaban had a lower risk for ischemic stroke or systemic embolism and for bleeding when compared with those receiving rivaroxaban. PRIMARY FUNDING SOURCE: National Institutes of Health.

Population-based screening to detect benzodiazepine drug-drug-drug interaction signals associated with unintentional traumatic injury.

Drug interactions involving benzodiazepines and related drugs (BZDs) are increasingly recognized as a contributor to increased risk of unintentional traumatic injury. Yet, it remains unknown to what extent drug interaction triads (3DIs) may amplify BZDs' inherent injury risk. We identified BZD 3DI signals associated with increased injury rates by conducting high-throughput pharmacoepidemiologic screening of 2000-2019 Optum's health insurance data. Using self-controlled case series design, we included patients aged ≥ 16 years with an injury while using a BZD + co-dispensed medication (i.e., base pair). During base pair-exposed observation time, we identified other co-dispensed medications as candidate interacting precipitants. Within each patient, we compared injury rates during time exposed to the drug triad versus to the base pair only using conditional Poisson regression, adjusting for time-varying covariates. We calculated rate ratios (RRs) with 95% confidence intervals (CIs) and accounted for multiple estimation via semi-Bayes shrinkage. Among the 65,123 BZD triads examined, 79 (0.1%) were associated with increased injury rates and considered 3DI signals. Adjusted RRs for signals ranged from 3.01 (95% CI = 1.53-5.94) for clonazepam + atorvastatin with cefuroxime to 1.42 (95% CI = 1.00-2.02, p = 0.049) for alprazolam + hydrocodone with tizanidine. These signals may help researchers prioritize future etiologic studies to investigate higher-order BZD interactions.

Trends in post-discharge prophylactic anticoagulant use among stroke patients in the United States between 2006 and 2019.

BACKGROUND: Stroke is an independent risk factor for venous thromboembolism (VTE). Although the risk of VTE persists after hospital discharge, information on the utilization of anticoagulants among stroke patients after discharge remains limited. OBJECTIVE: To evaluate changes in post-discharge thromboprophylaxis among stroke patients between 2006 and 2019. METHODS: We conducted a retrospective repeated cross-sectional analysis using a commercial healthcare insurance database in the United States. We included patients aged ≥ 18 years with incident stroke diagnosis and assessed prophylactic use of anticoagulants in the 30 days following hospital discharge including low-molecular-weight heparin (enoxaparin ≤40 mg/day, dalteparin ≤5000 IU/day), unfractionated heparin ≤5000 IU/ twice daily or 3 times a day, apixaban 2.5 mg twice daily, and rivaroxaban 10 mg/day. Patients with atrial fibrillation, VTE, mechanical heart valves, cancer, antiphospholipid antibody syndrome, and users of therapeutic doses of anticoagulants were excluded. We used the Cochrane-Armitage test to assess changes in the use of anticoagulants across the study period. RESULTS: There was a small increase in the overall use of post-discharge prophylactic anticoagulants among stroke patients between 2006 and 2019 from 0.5% to 1.9%. The use of heparin decreased from 0.5% in 2006 to 0.3% in 2019 (P-value for trend = 0.001). In contrast, the use of apixaban or rivaroxaban increased from 0.1% in 2013 to 1.6% in 2019 (P-value for trend < 0.001). Apixaban was more commonly used than rivaroxaban. CONCLUSIONS: In this population-based study of stroke patients, we found that post-discharge anticoagulant use remains low through 2019. Prophylactic use of heparin or rivaroxaban was relatively low but the use of apixaban increased over the study period. Further research is needed to determine if these agents are safe and effective for VTE prevention in stroke patients.

Identifying Clinically Relevant Drug-Drug Interactions With Methadone and Buprenorphine: A Translational Approach to Signal Detection.

Methadone and buprenorphine have pharmacologic properties that are concerning for a high risk of drug-drug interactions (DDIs). We performed high-throughput screening for clinically relevant DDIs with methadone or buprenorphine by combining pharmacoepidemiologic and pharmacokinetic approaches. We conducted pharmacoepidemiologic screening via a series of self-controlled case series studies (SCCS) in Optum claims data from 2000 to 2019. We included persons 18 years or older who experienced an outcome of interest during target drug treatment. Exposures were all overlapping medications (i.e., the candidate precipitants) during target drug treatment. Outcomes were opioid overdose, non-overdose adverse effects, and cardiac arrest. We used conditional Poisson regression to calculate rate ratios, accounting for multiple comparisons with semi-Bayes shrinkage. We explored the impact of key study design choices in analyses that varied the exposure definitions of the target drugs and the candidate precipitant drugs. Pharmacokinetic screening was conducted by incorporating published data on CYP enzyme metabolism into an equation-based static model. In SCCS analysis, 1,432 events were included from 248,069 new users of methadone or buprenorphine. In the primary analysis, statistically significant DDIs included gabapentinoids with either methadone or buprenorphine; baclofen with methadone; and benzodiazepines with methadone. In sensitivity analysis, additional statistically significant DDIs included methocarbamol, quetiapine, or simvastatin with methadone. Pharmacokinetic screening identified two moderate-to-strong potential DDIs (clonidine and fluconazole with buprenorphine). The combination of clonidine and buprenorphine was also associated with a significantly increased risk of opioid overdose in pharmacoepidemiologic screening. These DDI signals may be the most important targets for future confirmation studies.

Skeletal muscle relaxant drug-drug-drug interactions and unintentional traumatic injury: Screening to detect three-way drug interaction signals.

AIM: The aim of this study was to identify skeletal muscle relaxant (SMR) drug-drug-drug interaction (3DI) signals associated with increased rates of unintentional traumatic injury. METHODS: We conducted automated high-throughput pharmacoepidemiologic screening of 2000-2019 healthcare data for members of United States commercial and Medicare Advantage health plans. We performed a self-controlled case series study for each drug triad consisting of an SMR base-pair (i.e., concomitant use of an SMR with another medication), and a co-dispensed medication (i.e., candidate interacting precipitant) taken during ongoing use of the base-pair. We included patients aged ≥16 years with an injury occurring during base-pair-exposed observation time. We used conditional Poisson regression to calculate adjusted rate ratios (RRs) with 95% confidence intervals (CIs) for injury with each SMR base-pair + candidate interacting precipitant (i.e., triad) versus the SMR-containing base-pair alone. RESULTS: Among 58 478 triads, 29 were significantly positively associated with injury; confounder-adjusted RRs ranged from 1.39 (95% CI = 1.01-1.91) for tizanidine + omeprazole with gabapentin to 2.23 (95% CI = 1.02-4.87) for tizanidine + diclofenac with alprazolam. Most identified 3DI signals are new and have not been formally investigated. CONCLUSION: We identified 29 SMR 3DI signals associated with increased rates of injury. Future aetiologic studies should confirm or refute these SMR 3DI signals.

Outcomes of Direct Oral Anticoagulants in Patients with Atrial Fibrillation and Valvular Heart Disease.

PURPOSE OF REVIEW: Direct oral anticoagulants (DOACs) are increasingly used for the treatment and prevention of thromboembolic events in patients with non-valvular atrial fibrillation (AF). Evidence regarding their role in patients with AF and concurrent valvular heart disease (VHD) continues to evolve. RECENT FINDINGS: Post hoc analyses of randomized clinical trials suggest that DOACs are non-inferior to warfarin for the prevention of stroke or systemic embolism in patients with AF and VHD. Emerging evidence from observational data showed a favorable benefit-risk profile for DOACs compared to warfarin in patients with AF and VHD. DOACs are an attractive option for the treatment of patients with AF and VHD who cannot tolerate or have contraindications to warfarin therapy. Future studies are needed to evaluate their effectiveness, safety, and examine variability in the direction and magnitude of treatment effects in selected VHD subgroups.

Signals of Muscle Relaxant Drug Interactions Associated with Unintentional Traumatic Injury: A Population-Based Screening Study.

BACKGROUND: Use of muscle relaxants is rapidly increasing in the USA. Little is understood about the role of drug interactions in the known association between muscle relaxants and unintentional traumatic injury, a clinically important endpoint causing substantial morbidity, disability, and death. OBJECTIVE: We examined potential associations between concomitant drugs (i.e., precipitants) taken with muscle relaxants (affected drugs, i.e., objects) and hospital presentation for unintentional traumatic injury. METHODS: In a series of self-controlled case series studies, we screened to identify drug interaction signals for muscle relaxant + precipitant pairs and unintentional traumatic injury. We used Optum's de-identified Clinformatics® Data Mart Database, 2000-2019. We included new users of a muscle relaxant, aged 16-90 years, who were dispensed at least one precipitant drug and experienced an unintentional traumatic injury during the observation period. We classified each observation day as precipitant exposed or precipitant unexposed. The outcome was an emergency department or inpatient discharge diagnosis for unintentional traumatic injury. We used conditional Poisson regression to estimate rate ratios adjusting for time-varying confounders and then accounted for multiple estimation via semi-Bayes shrinkage. RESULTS: We identified 74,657 people who initiated muscle relaxants and experienced an unintentional traumatic injury, in whom we studied concomitant use of 2543 muscle relaxant + precipitant pairs. After adjusting for time-varying confounders, 16 (0.6%) pairs were statistically significantly and positively associated with injury, and therefore deemed signals of a potential drug interaction. Among signals, semi-Bayes shrunk, confounder-adjusted rate ratios ranged from 1.29 (95% confidence interval 1.04-1.62) for baclofen + sertraline to 2.28 (95% confidence interval 1.14-4.55) for methocarbamol + lamotrigine. CONCLUSIONS: Using real-world data, we identified several new signals of potential muscle relaxant drug interactions associated with unintentional traumatic injury. Only one among 16 signals is currently reported in a major drug interaction knowledge base. Future studies should seek to confirm or refute these signals.

Comparative Safety of Sodium-Glucose Cotransporter 2 Inhibitors Versus Dipeptidyl Peptidase 4 Inhibitors and Sulfonylureas on the Risk of Diabetic Ketoacidosis.

OBJECTIVE: To assess the association of sodium-glucose cotransporter 2 (SGLT2) inhibitors with diabetic ketoacidosis compared with dipeptidyl peptidase 4 (DPP-4) inhibitors and sulfonylureas in patients with type 2 diabetes. RESEARCH DESIGN AND METHODS: We conducted a new-user active comparator cohort study to examine two pairwise comparisons: 1) SGLT2 inhibitors versus DPP-4 inhibitors and 2) SGLT2 inhibitors versus sulfonylureas. The main outcome was diabetic ketoacidosis present on hospital admission. We adjusted for confounders through propensity score matching. We used Cox proportional hazards regression with a robust variance estimator to estimate hazard ratios (HRs) and corresponding 95% CIs while adjusting for calendar time. RESULTS: In cohort 1 (n = 85,125 for SGLT2 inhibitors and n = 85,125 for DPP-4 inhibitors), the incidence rates of diabetic ketoacidosis per 1,000 person-years were 6.0 and 4.3 for SGLT2 inhibitors and DPP4 inhibitors, respectively. In cohort 2 (n = 72,436 for SGLT2 inhibitors and n = 72,436 for sulfonylureas), the incidence rates of diabetic ketoacidosis per 1,000 person-years were 6.3 and 4.5 for SGLT2 inhibitors and sulfonylureas, respectively. In Cox proportional hazards regression models, the use of SGLT2 inhibitors was associated with a higher rate of diabetic ketoacidosis compared with DPP-4 inhibitors (adjusted HR [aHR] 1.63; 95% CI 1.36, 1.96) and sulfonylureas (aHR 1.56; 95% CI 1.30, 1.87). CONCLUSIONS: In this comparative safety study using real-world data, patients with type 2 diabetes who were newly prescribed SGLT2 inhibitors had a higher rate of diabetic ketoacidosis compared with DPP-4 inhibitors and sulfonylureas. Clinicians should be vigilant about this association.

Comparative Safety of Dipeptidyl Peptidase-4 Inhibitors and Sudden Cardiac Arrest and Ventricular Arrhythmia: Population-Based Cohort Studies.

In vivo studies suggest that arrhythmia risk may be greater with less selective dipeptidyl peptidase-4 inhibitors, but evidence from population-based studies is missing. We aimed to compare saxagliptin, sitagliptin, and linagliptin with regard to risk of sudden cardiac arrest (SCA)/ventricular arrhythmia (VA). We conducted high-dimensional propensity score (hdPS) matched, new-user cohort studies. We analyzed Medicaid and Optum Clinformatics separately. We identified new users of saxagliptin, sitagliptin (both databases), and linagliptin (Optum only). We defined SCA/VA outcomes using emergency department and inpatient diagnoses. We identified and then controlled for confounders via a data-adaptive, hdPS approach. We generated marginal hazard ratios (HRs) via Cox proportional hazards regression using a robust variance estimator while adjusting for calendar year. We identified the following matched comparisons: saxagliptin vs. sitagliptin (23,895 vs. 96,972) in Medicaid, saxagliptin vs. sitagliptin (48,388 vs. 117,383) in Optum, and linagliptin vs. sitagliptin (36,820 vs. 78,701) in Optum. In Medicaid, use of saxagliptin (vs. sitagliptin) was associated with an increased rate of SCA/VA (adjusted HR (aHR), 2.01, 95% confidence interval (CI) 1.24-3.25). However, in Optum data, this finding was not present (aHR, 0.79, 95% CI 0.41-1.51). Further, we found no association between linagliptin (vs. sitagliptin) and SCA/VA (aHR, 0.65, 95% CI 0.36-1.17). We found discordant results regarding the association between SCA/VA with saxagliptin compared with sitagliptin in two independent datasets. It remains unclear whether these findings are due to heterogeneity of treatment effect in the different populations, chance, or unmeasured confounding.

Long-term Outcomes Following Multiply Recurrent Clostridioides difficile Infection and Fecal Microbiota Transplantation.

BACKGROUND AND AIMS: Fecal microbiota transplantation (FMT) is a commonly used therapy for multiply recurrent Clostridioides difficile (mrCDI). By altering the gut microbiota, there is the potential for FMT to impact the risk for cardiometabolic, intestinal or immune-mediated conditions. Likewise, the microbiota disturbance associated with mrCDI could potentially lead to these conditions. We aimed to assess the associations of mrCDI and FMT with cardiometabolic, immune-mediated diseases, and irritable bowel syndrome. METHODS: This retrospective cohort study using a United States commercial claims database included persons diagnosed with CDI or undergoing FMT. We created 2 pairwise comparisons: mrCDI vs non-mrCDI, and non-mrCDI or mrCDI treated with FMT vs mrCDI without FMT. RESULTS: We found no significant association between mrCDI (vs non-mrCDI) and inflammatory bowel disease (adjusted hazard ratio (aHR) = 1.65; 95% confidence interval, 0.67-4.04), rheumatoid arthritis (HR = 0.86; 0.47-1.56), psoriasis (HR = 0.72; 0.23-2.27), diabetes (aHR = 0.97; 0.67-1.40), hypertension (aHR = 1.05; 0.76-1.44), myocardial infarction (aHR = 0.82; 0.63-1.06), stroke (aHR = 0.83; 0.62-1.12), or irritable bowel syndrome (HR = 0.94; 0.61-1.45). Similarly, we found no association of CDI with FMT (vs mrCDI without FMT) and diabetes (aHR = 0.92; 0.27-3.11), hypertension (aHR = 1.41; 0.64-3.15), stroke (aHR = 1.27; 0.69-2.34) or inflammatory bowel syndrome (aHR = 0.80; 0.26-2.46). However, the incidence of myocardial infarction was increased following FMT (aHR = 1.68; 1.01-2.81). CONCLUSION: Relative to those with CDI, persons with mrCDI do not appear to be intrinsically at higher risk of cardiometabolic, immune-mediated diseases, or irritable bowel syndrome. However, those who underwent FMT for CDI had a higher incidence of myocardial infarction. Future studies should assess this association to assess reproducibility.

Risk for Recurrent Venous Thromboembolism and Bleeding With Apixaban Compared With Rivaroxaban: An Analysis of Real-World Data.

BACKGROUND: Apixaban and rivaroxaban are replacing vitamin K antagonists for the treatment of venous thromboembolism (VTE) in adults; however, head-to-head comparisons remain limited. OBJECTIVE: To assess the effectiveness and safety of apixaban compared with rivaroxaban in patients with VTE. DESIGN: Retrospective new-user cohort study. SETTING: U.S.-based commercial health care insurance database from 1 January 2015 to 30 June 2020. PARTICIPANTS: Adults with VTE who were newly prescribed apixaban or rivaroxaban. MEASUREMENTS: The primary effectiveness outcome was recurrent VTE, a composite of deep venous thrombosis and pulmonary embolism. The primary safety outcome was a composite of gastrointestinal and intracranial bleeding. RESULTS: Of 49 900 eligible patients with VTE, 18 618 were new users of apixaban and 18 618 were new users of rivaroxaban. Median follow-up was 102 days (25th, 75th percentiles: 30, 128 days) among apixaban and 105 days (25th, 75th percentiles: 30, 140 days) among rivaroxaban users. After propensity score matching, apixaban (vs. rivaroxaban) was associated with a lower rate for recurrent VTE (hazard ratio, 0.77 [95% CI, 0.69 to 0.87]) and bleeding (hazard ratio, 0.60 [CI, 0.53 to 0.69]). The absolute reduction in the probability of recurrent VTE with apixaban versus rivaroxaban was 0.006 (CI, 0.005 to 0.011) within 2 months and 0.011 (CI, 0.011 to 0.013) within 6 months of initiation. The absolute reduction in the probability of gastrointestinal and intracranial bleeding with apixaban versus rivaroxaban was 0.011 (CI, 0.010 to 0.011) within 2 months and 0.015 (CI, 0.013 to 0.015) within 6 months of initiation. LIMITATION: Short follow-up. CONCLUSION: In this population-based cohort study, patients with VTE who were new users of apixaban had lower rates for recurrent VTE and bleeding than new users of rivaroxaban. PRIMARY FUNDING SOURCE: None.

Cardiovascular and major bleeding outcomes with antiplatelet and direct oral anticoagulants in patients with acute coronary syndrome and atrial fibrillation: A population-based analysis.

BACKGROUND: Direct oral anticoagulants (DOACs) are replacing warfarin for stroke prevention in patients with atrial fibrillation (AF). OBJECTIVE: To assess the effectiveness and safety of concomitant treatment with antiplatelet-DOAC compared to antiplatelet-warfarin in patients with acute coronary syndrome (ACS) and AF. DESIGN: Retrospective propensity score-matched cohort study using United States-based commercial healthcare database from January 2016 to June 2019. PARTICIPANTS: New-users of antiplatelet-DOAC and antiplatelet-warfarin who initiated the combined therapy within 30 days following incident ACS diagnosis. MEASUREMENTS: Primary study outcomes were recurrent cardiovascular diseases (CVD) (ie, a composite of stroke and myocardial infarction) and major bleeding events identified via discharge diagnoses. We controlled for potential confounders via propensity score matching (PSM). We generated marginal hazard ratios (HRs) via Cox proportional hazards regression using a robust variance estimator while adjusting for calendar time. RESULTS: After PSM, a total of 2,472 persons were included (1,236 users of antiplatelet-DOAC and 1,236 users of antiplatelet-warfarin). The use of antiplatelet-DOAC (vs. antiplatelet-warfarin) was associated with a reduced rate of recurrent CVD (adjusted HR 0.72, 95% confidence interval [CI], 0.56-0.92) and major bleeding events (adjusted HR, 0.49, 95% CI 0.33-0.72). LIMITATIONS: Residual confounding. CONCLUSIONS: In real-world data of AF patients with concurrent ACS, the use of antiplatelet-DOAC following ACS diagnosis was associated with a lower rate of recurrent CVD and major bleeding events compared with antiplatelet-warfarin. These findings highlight a potential promising role for DOACs in patients with ACS and AF requiring combined antiplatelet therapy.

Compared to commercially insured patients, Medicare advantage patients adopt newer diabetes drugs more slowly and adhere to them less.

AIMS: To compare rates of use and adherence for newer versus older second-line diabetes drug classes in commercially insured, Medicare Advantage and dual-eligible (covered by both Medicare and Medicaid) patients. MATERIALS AND METHODS: Longitudinal cohort study using insurance claims data from 1/1/2012 to 12/31/2016 to identify patients with a first prescription, after metformin, of a second-line diabetes drug (eg sulphonylurea, DPP-4 inhibitor, thiazolidinedione, SGLT-2 inhibitor or GLP-1 receptor agonist) and to estimate their adherence to that drug class. Univariate analysis and multivariable logistic regression were used to examine the association between insurance type and use of each drug class, and between insurance type and adherence to each drug class. RESULTS: The study population included 96,663 patients. Trends in drug use differed by insurance type. For example, sulphonylurea use declined among the commercially insured (from 46% to 39%, p < .001) but not among Medicare Advantage or dual-eligible patients. Patterns of adherence also differed between insurance groups. For example, compared to commercial insurance, Medicare Advantage was associated with higher adherence to sulphonylurea (odds ratio [OR] 1.32, 95% CI 1.21-1.43)) but lower adherence to SGLT-2 inhibitors (OR 0.43 (95% CI 0.33-0.56)). CONCLUSIONS: This study finds differences in utilization and adherence for diabetes drugs across insurance types. Older medications such as sulphonylureas appear to be more used and better adhered to among Medicare Advantage recipients, while the opposite is true for newer medication classes. These findings suggest a need to personalize selection of diabetes drugs according to insurance status, particularly when adherence needs optimization.

Effectiveness and Safety of Direct Oral Anticoagulants Versus Warfarin in Patients With Valvular Atrial Fibrillation : A Population-Based Cohort Study.

BACKGROUND: Direct oral anticoagulants (DOACs) are increasingly used in place of warfarin, but evidence about their effectiveness and safety in patients with valvular atrial fibrillation (AF) remains limited. OBJECTIVE: To assess the effectiveness and safety of DOACs compared with warfarin in patients with valvular AF. DESIGN: New-user retrospective propensity score-matched cohort study. SETTING: U.S.-based commercial health care database from 1 January 2010 to 30 June 2019. PARTICIPANTS: Adults with valvular AF who were newly prescribed DOACs or warfarin. MEASUREMENTS: The primary effectiveness outcome was a composite of ischemic stroke or systemic embolism. The primary safety outcome was a composite of intracranial or gastrointestinal bleeding. RESULTS: Among a total of 56 336 patients with valvular AF matched on propensity score, use of DOACs (vs. warfarin) was associated with lower risk for ischemic stroke or systemic embolism (hazard ratio [HR], 0.64 [95% CI, 0.59 to 0.70]) and major bleeding events (HR, 0.67 [CI, 0.63 to 0.72]). The results for the effectiveness and safety outcomes remained consistent for apixaban (HRs, 0.54 [CI, 0.47 to 0.61] and 0.52 [CI, 0.47 to 0.57], respectively) and rivaroxaban (HRs, 0.74 [CI, 0.64 to 0.86] and 0.87 [CI, 0.79 to 0.96], respectively); with dabigatran, results were consistent for the major bleeding outcome (HR, 0.81 [CI, 0.68 to 0.97]) but not for effectiveness (HR, 1.03 [CI, 0.81 to 1.31]). LIMITATION: Relatively short follow-up; inability to ascertain disease severity. CONCLUSION: In this comparative effectiveness study using practice-based claims data, patients with valvular AF who were new users of DOACs had lower risks for ischemic stroke or systemic embolism and major bleeding than new users of warfarin. These data may be used to guide risk-benefit discussions regarding anticoagulant choices for patients with valvular AF. PRIMARY FUNDING SOURCE: None.