United States Clinical Practice Research Articles

Low-density lipoprotein cholesterol lowering in real-world patients treated with evolocumab.

BackgroundLow‐density lipoprotein cholesterol (LDL‐C) is a risk factor for atherosclerotic cardiovascular disease (ASCVD). There are limited real‐world data on LDL‐C lowering with evolocumab in United States clinical practice.HypothesisWe assessed LDL‐C lowering during 1 year of evolocumab therapy.MethodsThis retrospective cohort study used linked laboratory (Prognos) and medical claims (IQVIA Dx/LRx and PharMetrics Plus®) data. Patients with a first fill for evolocumab between 7/1/2015 and 10/31/2019 (index event) and LDL‐C ≥ 70 mg/dL were included (overall cohort; N = 5897). Additionally, a patient subgroup with a recent myocardial infarction (MI) within 12 months (median 130 days) before the first evolocumab fill was identified (N = 152). Reduction from baseline LDL‐C was calculated based on the lowest LDL‐C value recorded during a 12‐month follow‐up period.ResultsThe mean (SD) age was 65 (10) years; 61.9% of patients had ASCVD diagnoses and 70.7% of patients were in receipt of lipid‐lowering therapy. Following evolocumab treatment, changes in LDL‐C from baseline were −60% in the overall cohort (median [interquartile range (IQR)] 146 [115–180] mg/dL to 58 [36–84] mg/dL) and −65% in the recent MI subgroup (median [IQR] 137 [109–165] mg/dL to 48 [30–78] mg/dL). In the overall cohort and recent MI subgroup, 62.1% and 69.7% of patients achieved LDL‐C < 70 mg/dL, respectively.ConclusionsIn this real‐world analysis, evolocumab was associated with significant reductions in LDL‐C comparable to that seen in the FOURIER clinical trial, which were durable over 1 year of treatment.

HSR21-051: Treatment Outcomes Among HR+/HER2- Advanced/Metastatic Breast Cancer Patients Receiving CDK 4 &amp; 6 Inhibitors in a United States Clinical Practice Setting

"HSR21-051: Treatment Outcomes Among HR+/HER2- Advanced/Metastatic Breast Cancer Patients Receiving CDK 4 & 6 Inhibitors in a United States Clinical Practice Setting" published on 17 Mar 2021 by National Comprehensive Cancer Network.

The demise of islet allotransplantation in the United States: A call for an urgent regulatory update.

Islet allotransplantation in the United States (US) is facing an imminent demise. Despite nearly three decades of progress in the field, an archaic regulatory framework has stymied US clinical practice. Current regulations do not reflect the state-of-the-art in clinical or technical practices. In the US, islets are considered biologic drugs and "more than minimally manipulated" human cell and tissue products (HCT/Ps). In contrast, across the world, human islets are appropriately defined as "minimally manipulated tissue" and not regulated as a drug, which has led to islet allotransplantation (allo-ITx) becoming a standard-of-care procedure for selected patients with type 1 diabetes mellitus. This regulatory distinction impedes patient access to islets for transplantation in the US. As a result only 11 patients underwent allo-ITx in the US between 2016 and 2019, and all as investigational procedures in the settings of a clinical trials. Herein, we describe the current regulations pertaining to islet transplantation in the United States. We explore the progress which has been made in the field and demonstrate why the regulatory framework must be updated to both better reflect our current clinical practice and to deal with upcoming challenges. We propose specific updates to current regulations which are required for the renaissance of ethical, safe, effective, and affordable allo-ITx in the United States.

Design of the Association of Uterine Perforation and Expulsion of Intrauterine Device study: a multisite retrospective cohort study

Intrauterine devices are effective and safe, long-acting reversible contraceptives, but the risk of uterine perforation occurs with an estimated incidence of 1 to 2 per 1000 insertions. The European Active Surveillance Study for Intrauterine Devices, a European prospective observational study that enrolled 61,448 participants (2006-2012), found that women breastfeeding at the time of device insertion or with the device inserted at ≤36 weeks after delivery had a higher risk of uterine perforation. The Association of Uterine Perforation and Expulsion of Intrauterine Device (APEX-IUD) study was a Food and Drug Administration-mandated study designed to reflect current United States clinical practice. The aims of the APEX-IUD study were to evaluate the risk of intrauterine device-related uterine perforation and device expulsion among women who were breastfeeding or within 12 months after delivery at insertion. We aimed to describe the APEX-IUD study design, methodology, and analytical plan and present population characteristics, size of risk factor groups, and duration of follow-up. APEX-IUD study was a retrospective cohort study conducted in 4 organizations with access to electronic health records: Kaiser Permanente Northern California, Kaiser Permanente Southern California, Kaiser Permanente Washington, and Regenstrief Institute in Indiana. Variables were identified through structured data (eg, diagnostic, procedural, medication codes) and unstructured data (eg, clinical notes) via natural language processing. Outcomes include uterine perforation and device expulsion; potential risk factors were breastfeeding at insertion, postpartum timing of insertion, device type, and menorrhagia diagnosis in the year before insertion. Covariates include demographic characteristics, clinical characteristics, and procedure-related variables, such as difficult insertion. The first potential date of inclusion for eligible women varies by research site (from January 1, 2001 to January 1, 2010). Follow-up begins at insertion and ends at first occurrence of an outcome of interest, a censoring event (device removal or reinsertion, pregnancy, hysterectomy, sterilization, device expiration, death, disenrollment, last clinical encounter), or end of the study period (June 30, 2018). Comparisons of levels of exposure variables were made using Cox regression models with confounding adjusted by propensity score weighting using overlap weights. The study population includes 326,658 women with at least 1 device insertion during the study period (Kaiser Permanente Northern California, 161,442; Kaiser Permanente Southern California, 123,214; Kaiser Permanente Washington, 20,526; Regenstrief Institute, 21,476). The median duration of continuous enrollment was 90 (site medians 74-177) months. The mean age was 32 years, and the population was racially and ethnically diverse across the 4 sites. The mean body mass index was 28.5 kg/m2, and of the women included in the study, 10.0% had menorrhagia ≤12 months before insertion, 5.3% had uterine fibroids, and 10% were recent smokers; furthermore, among these women, 79.4% had levonorgestrel-releasing devices, and 19.5% had copper devices. Across sites, 97,824 women had an intrauterine device insertion at ≤52 weeks after delivery, of which 94,817 women (97%) had breastfeeding status at insertion determined; in addition, 228,834 women had intrauterine device insertion at >52 weeks after delivery or no evidence of a delivery in their health record. Combining retrospective data from multiple sites allowed for a large and diverse study population. Collaboration with clinicians in the study design and validation of outcomes ensured that the APEX-IUD study results reflect current United States clinical practice. Results from this study will provide valuable information based on real-world evidence about risk factors for intrauterine devices perforation and expulsion for clinicians.

Contemporary procedural trends of Watchman percutaneous left atrial appendage occlusion in the United States.

To determine trends in real-world utilization and in-hospital adverse events from Watchman implantation since its approval by the Food and Drug Administration in 2015. The risk of embolic stroke caused by atrial fibrillation is reduced by oral anticoagulants, but not all patients can tolerate long-term anticoagulation. Left atrial appendage occlusion with the Watchman device has emerged as an alternative therapy. This was a retrospective cohort study utilizing data from National Inpatient Sample for calendar years 2015-2017. The outcomes assessed in this study were associated complications, in-hospital mortality, and resource utilization trends after Watchman implantation. Trends analysis were performed using analysis of variance. Multivariable adjusted logistic regression analysis was performed to determine predictors of mortality. A total of 17 700 patients underwent Watchman implantation during the study period. There was a significantly increased trend in the number of Watchman procedures performed over the study years (from 1195 in 2015 to 11 165 devices in 2017, p < .01). A significant decline in the rate of complications (from 26.4% in 2015% to 7.9% in 2017, p < .01) and inpatient mortality (from 1.3% in 2015% to 0.1% in 2017, p < .01) were noted. Predictors of in-hospital mortality included a higher CHA2 DS2 -VASc score (odds ratio [OR]: 2.61 per 1-point increase, 95% confidence interval [CI]: 1.91-3.57), chronic blood loss anemia (OR:3.63, 95% CI: 1.37-9.61) and coagulopathy (OR: 4.90, 95% CI: 2.32-10.35). In contemporary United States clinical practice, Watchman utilization has increased significantly since approval in 2015, while complications and in-patient mortality have declined.

Characteristics and Treatment Patterns of Newly Diagnosed Open-Angle Glaucoma Patients in the United States: An Administrative Database Analysis

To characterize newly diagnosed primary open-angle glaucoma (OAG) patients and to describe their treatment journey in United States clinical practice according to the use of topical therapy, laser trabeculoplasty, and surgical procedures. Retrospective claims database study. Patients with at least 2 diagnoses of OAG 7 days or more apart and within 1 year, with the first (index) diagnosis in 2010, at least 30 months of continuous enrollment before index diagnosis with no OAG diagnosis or medication (exception for ocular hypertension diagnosis), and 48 months of continuous enrollment. Analysis of United States healthcare insurance claims database (July 2007-December 2014). Treatment patterns and ophthalmology visits were evaluated over 48 months in 4 cohorts based on initial therapy after the index diagnosis: (1) drug monotherapy, (2) combination drug therapy, (3) glaucoma procedure, or (4) no claims for treatment. Treatment modification was defined as an addition to or change in drug therapy or procedure. In total, 83.0% of patients (5120/6172) began a drug therapy (69.5%) or underwent a procedure initially (13.5%); topical prostaglandin analogs (n= 2887/5120 [56.4%]) and laser trabeculoplasty (n= 705/5120 [13.8%]) were the most common. During the 4-year follow-up, 58.3% of patients (2109/3620) who began drug monotherapy experienced no further treatment modification. Over this period, 43.8% of patients who began treatment (2242/5120) experienced a treatment modification to the first treatment. Two thirds (1505/2242 [67.1%]) of these patients subsequently underwent a third treatment modification. Ophthalmology visits declined over time regardless of initial therapy, with the greatest decrease among the untreated and first-treatment procedure cohorts. The high rates of 2 or 3 treatment modifications over the 4-year period suggest an unmet need for glaucoma therapies with durable and predictable actions.

Increased Bacillus Calmette-Guérin Treatment Intensity Associated With Improved Outcomes in Elderly Patients With Non–Muscle-invasive Bladder Cancer in United States Clinical Practice

To characterize Bacillus Calmette-Guérin (BCG) treatment patterns and associated outcomes in a large cohort of patients with non-muscle-invasive bladder cancer (NMIBC). Our retrospective analysis of patients aged ≥66 years with stage 0-1 urothelial bladder carcinoma diagnosed between 2000 and 2012 in the United States Surveillance, Epidemiology, and End Results-Medicare database estimated proxies for recurrence and secondary events and both all-cause and bladder cancer-specific mortality. Proportional hazards models were used in conditional landmark analyses to compare adequate (≥5 induction instillations and ≥2 maintenance instillations) and inadequate BCG, stratified by National Comprehensive Cancer Network risk group. Of 39,532 patients who met the selection criteria, 16,225 (41.0%) received BCG; of them, 4602 (28.4%; 11.6% overall) received adequate treatment. Adequately treated patients were slightly younger and healthier than inadequately treated patients. Half of patients with intermediate- and high-risk NMIBC did not receive BCG; few received adequate treatment. At the 12-month landmark, adequate BCG treatment was associated with decreased risks of recurrence and of cancer-specific and all-cause mortality in patients with intermediate- and high-risk disease. We observed lower than expected use of adequate BCG treatment in patients with intermediate- to high-risk NMIBC despite evidence of improved outcomes, which suggested that practice patterns may not be in line with management recommendations in this population.

Management and Outcomes for Neovascular Age-Related Macular Degeneration: Analysis of United States Electronic Health Records

To assess anti-vascular endothelial growth factor (VEGF) management patterns and anatomic and visual acuity (VA) outcomes among patients with neovascular age-related macular degeneration (nAMD) in United States clinical practice. Retrospective observational cohort study. Patients (N = 30 106) initiating intravitreal anti-VEGF treatment for nAMD between October 2009 and November2016. Analysis of longitudinal electronic health records from USRetina. Number of intravitreal injections, OCT examinations, and fluorescein angiography (FA) examinations per study eye during the first 12 months; corrected VA and central retinal thickness (CRT) at 12 months; and number of ophthalmologist visits, stratified by index anti-VEGF agent. Over the first 12 months, patients made a mean of 8.1 (range, 1-39) ophthalmologist visits, received a mean of 6.0 (range, 1-27) anti-VEGF injections, and underwent 7.2 OCT and 5.3 FA examinations per study eye. For eyes with paired baseline and 12-month readings, mean CRT declined from 320 to 271 μm (mean change, -48 μm), and mean VA increased from 60.3 to 61.0 approximate Early Treatment Diabetic Retinopathy Study (ETDRS) letters (mean change,+0.6 letters). Twelve months after initiating index treatment with bevacizumab, ranibizumab, and aflibercept, 19.3%, 15.8%, and 15.5% of eyes, respectively, showed greater than 10-letter gain, whereas 13.2%, 14.7%, and 14.4% of eyes, respectively, showed greater than 10-letter loss. Mean change from baseline VA at 12 months increased linearly with cumulative anti-VEGF injection count:+1.79 versus -0.95 approximate ETDRS letters for eyes receiving 7 or more injections versus fewer than 7 injections. Similarly, the magnitude of the reduction from baseline CRT at 12 months tended to increase linearly with increasing number of anti-VEGF injections. Multivariate linear regression analysis, adjusted for covariates, indicated a significant association between cumulative number of anti-VEGF injections and change from baseline in VA at 12 months, with each unit increase producing an estimated gain of 0.37 approximate ETDRS letters. This analysis of combined morphologic and functional outcomes of anti-VEGF therapy, the largest conducted to date in nAMD, identified relatively low anti-VEGF injection frequencies, coupled withmoderate anatomic and limited VA improvements, in United States clinical practice.

Treatment (tx) characteristics of patients (pts) with locally advanced or metastatic urothelial cancer (mUC) receiving atezolizumab (atezo) monotherapy in United States clinical practice.

381 Background: Atezo (anti–PD-L1) was the first immune checkpoint inhibitor approved for mUC. Here, we describe pt characteristics, time on tx (TOT) and distribution of tx cycles for pts receiving atezo in clinical practice, to complement data from clinical trial setting. Methods: Pts diagnosed with mUC who initiated atezo monotherapy in the first-line (1L) or second-line and beyond (2L+; prior platinum tx) settings on or before Jun 30, 2017, were identified from the US-based Flatiron Health electronic health record–derived database. Tx data were analyzed through Mar 31, 2018. TOT was defined as time from first to last atezo administration, plus 1 cycle length. Median TOT was calculated by tx line using the Kaplan-Meier method. Tx cycles were calculated by the number of atezo doses received during TOT. Corresponding results from global atezo clinical trials are presented. Results: Real-world data (RWD) from 312 pts (n = 102, 1L; n = 210, 2L+) met the study selection criteria (Table). Median TOT was 3 and 3.5 months in the 1L and 2L+ settings, respectively, with 95% CIs overlapping with the trial TOT data. A median of 4 cycles (IQR, 2-7, 1L; 2-9, 2L+) was administered in both settings. Conclusions: This is the first study of RW atezo use in mUC. The TOT with atezo observed in a US RW setting and the clinical setting (IMvigor210/IMvigor211) was similar. [Table: see text]

Predictors of receipt of immunotherapy for stage II and III melanoma in United States clinical practice.

e20003 Background: Recent National Comprehensive Cancer Network guidelines for management of early stage resected melanoma highlight the significance of tumor pathology and involved lymph nodes in ...

Safety and Efficacy of the XIENCE V Everolimus-Eluting Stent Compared to First-Generation Drug-Eluting Stents in Contemporary Clinical Practice

Data from randomized clinical trials have shown the safety and efficacy of the XIENCE V in selected populations. However, limited data are available comparing the XIENCE V to the first-generation CYPHER sirolimus-eluting stent. This study aimed to assess the long-term safety and clinical efficacy of the XIENCE V everolimus-eluting stent compared to first-generation stents in an unselected patient population. This retrospective analysis included 6,069 patients treated with CYPHER, TAXUS, and XIENCE stents from 2003 to 2009 at our institution. The patients were followed up for ≥1 year after the index procedure. The baseline characteristics were generally comparable among the 3 groups, with the exception of a significantly greater prevalence of diabetes mellitus, systemic hypertension, and a history of angioplasty and coronary bypass surgery among the XIENCE patients. The XIENCE patients also had a twofold greater rate of type C lesions. One-year follow-up data were available for 82% of the patients. The 1-year major adverse cardiovascular events rate was 9.3% for the XIENCE stent versus 9.8% for the CYPHER stent and 11.5% for the TAXUS stent (p = 0.11). Mortality was lower in the XIENCE group than in the CYPHER and TAXUS groups (3.6% vs 4.9% vs 7.2%, respectively, p <0.001), and target lesion revascularization was similar (5.9% vs 5.2% vs 5.6%, respectively; p = 0.34). Stent thrombosis was lower in the XIENCE patients (0.2% vs 1.2% vs 0.7%, p = 0.007). In conclusion, in a contemporary United States clinical practice with an unselected patient population, use of the XIENCE V stent was associated with an improved safety profile and reduction of all-cause mortality and stent thrombosis compared to first-generation drug-eluting stents. The XIENCE V failed to demonstrate superiority for overall major adverse cardiovascular events, Q-wave myocardial infarction, and revascularization rates.

Discontinuation of Lipid Modifying Drugs Among Commercially Insured United States Patients in Recent Clinical Practice

Although several lipid-modifying drug (LMD) treatments and strategies are available to successfully manage patients at risk for cardiovascular events, the benefits of drug treatment can be realized only if these therapies are continued on a long-term basis. Previous observational studies examining rates of discontinuation with LMDs are not generalizable to current clinical practice in the United States. In this study, the discontinuation of newly initiated LMD classes in recent clinical practice was compared in a geographically diverse, commercially insured United States population. Administrative claims from the Ingenix Lab/Rx Database were used to identify patients aged >or=20 years who were newly prescribed statins, extended-release niacin, fibrates, bile acid sequestrants, or ezetimibe from January 1, 2001, to June 30, 2003. An LMD class was considered discontinued if a patient did not receive a prescription from the same LMD class within 180 days of the most recent prescription expiration date. The median time to discontinuation was 8.2 months in the bile acid sequestrant group, followed by 12 months in the extended-release niacin group, 17.4 months in the fibrate group, and 27.5 months in the statin group. By the end of 1 year, the adjusted cumulative incidence of discontinuation was 68.3% in bile acid sequestrant users, 55.4% in extended-release niacin users, 39.9% in fibrate users, 33.0% in ezetimibe users, and 28.9% in statin users (p <0.001 for all LMD classes vs statins). In conclusion, despite the changes in lipid treatment paradigms and the importance of long-term lipid therapy, this study found high discontinuation rates of LMD classes in recent United States clinical practice.