Real-world Patient Population Research Articles

Analysis of inactivating TSC1 and TSC2 alterations in a real-world patient population with advanced gynecologic cancers in the Foundation Medicine genomic database

Analysis of inactivating TSC1 and TSC2 alterations in a real-world patient population with advanced gynecologic cancers in the Foundation Medicine genomic database

The prognostic value of contrast stress echocardiography in a real-world population of symptomatic patients without known coronary artery disease

Abstract Background Coronary artery disease (CAD) is the leading cause of mortality and morbidity worldwide. In addition to diagnosis, non-invasive tests may also provide prognostic information useful in the risk stratification and management of CAD patients. Stress echocardiography (SE) is an accurate, non-invasive method for the detection of obstructive CAD. However, in real-world clinical practice the test performance may vary among different centres, depending on availability, local protocols, and operator expertise. Purpose To evaluate the prognostic value of contrast SE in a real-world population of symptomatic patients without known CAD. Methods This was a cohort follow-up study of patients without known CAD and symptoms of atypical chest pain, unexplained dyspnoea or palpitations who were referred to the echocardiography lab of a tertiary hospital for SE between January 2020 and December 2021. Patients with resting regional wall motion abnormalities were excluded. All patients underwent treadmill exercise stress echocardiography (ESE) or dobutamine stress echocardiography (DSE) if unable to exercise. Contrast agents were used in almost all patients (99%). The study population was followed-up for at least 2 years after SE by phone and/or electronic hospital records. Cardiac outcome was defined as anatomically or functionally significant stenosis on angiography, revascularization, acute coronary syndrome (ACS), or cardiac-related death. Results The study comprised 266 patients (mean age 58±12 years, 63% male) who underwent either ESE (58%) or DSE (42%). The patients' details are reported in Table 1. The most common indication for the exam was atypical chest pain, with a prevalence of 73%. SE exams were positive for inducible ischaemia in 14 (5%) patients. Symptoms during the exam were present in 3 (21%) patients with positive SE and 4 patients (2%) with negative SE (p=0.004). No serious complications (sustained ventricular tachycardia, myocardial infarction, or death) were recorded. During the follow-up (median 30, IQR 23–38 months), 264 patients (99%) were successfully contacted. Cardiac outcome occurred in 10 patients. Among 14 patients with positive SE, 8 underwent revascularization due to significant coronary artery stenosis. Among 250 patients with negative SE, 1 underwent revascularization due to significant coronary artery stenosis and 1 presented with ACS 13 months after the test (both patients underwent DSE). Negative predictive value was 99% over a median follow-up of 30 months, corresponding to an annualized event rate of 0.32% per year. A positive SE was significantly associated with cardiac outcome (log-rank test p<0.0001, Figure 1). Conclusion Contrast SE carries significant prognostic implications in symptomatic patients without known CAD. A positive test is strongly associated with the need for revascularization, while a normal test result has an excellent negative predictive value regarding cardiovascular morbidity and mortality.Figure 1

GLP1-RA versus DPP4 inhibitors on cardiovascular outcomes: A three-year real-world analysis

Abstract Background Cardiovascular outcome trials of GLP1-RAs have massively impacted the clinical practice in the management of patients with type 2 diabetes. The cardiovascular protective properties of GLP1-RA compared to DPP4 have been demonstrated in an observational setting before, however recent methodological developments have enabled clinically relevant effect estimation. Aim This study aimed to evaluate the real-world cardiovascular outcomes of GLP1-RA versus DPP4 inhibitors in patients with type 2 diabetes and high cardiovascular risk. Methods In this study, we utilized the Danish nationwide registers to identify new users of GLP1-RA or DPP4 therapies from 2012 to 2022. Participants were required to be either at least 50 years of age and have one or more of the following conditions: hypertension, chronic obstructive pulmonary disease, cardiovascular disease, or chronic renal disease or be at least 60 years of age and have hypertension. Additionally, their glycated hemoglobin (HbA1c) levels needed to be 53 mmol/mol or higher within the year preceding their first prescription date for these therapies. The index date was defined as the initial prescription date, and comorbidities and medicine use were evaluated up to 10 years prior to this date. Individuals who had filled prescriptions for SGLT2 inhibitors within six months prior to their index date were excluded from the study. The outcome of interest was a composite of cardiovascular death, nonfatal myocardial infarction, or nonfatal stroke (MACE). Patients were followed for up to three years until MACE, all-cause mortality, emigration, or until the end of follow-up on December 31, 2022. To assess the three-year risk of MACE, the Aalen Johansson estimator was used. A casual inference framework was employed estimating the three-year average treatment effect using g-formula based on Cox regression with competing risk. Results A total of 26,190 individuals were included, with 19,494 initiating DPP4 inhibitor therapy and 6,696 initiating GLP1-RA therapy. The three-year risk of MACE was 8.56% (95% confidence interval [CI]: 8.11 to 9.00) for the DPP4 initiator group, compared to 4.76% (95% CI: 4.08 to 5.43) for the GLP1-RA initiator group. Emulating what would have happened had all included individuals initiated GLP1-RA treatment versus had all initiated treatment with DPP4, accounting for age, sex, income, education, degree of urbanization, diabetes duration, baseline hba1c level, co-medicine, and co-morbidities, we estimated an three-year average treatment effect of -2.05% (95% CI:-2.92;-1.18) , p-value<0.001) for GLP1-RA initiation versus DPP4 initiation for MACE. Conclusion Our findings suggest that GLP1-RA use is associated with a significantly lower risk of MACE compared to DPP4 inhibitors in a real-world population of patients with type 2 diabetes and high cardiovascular risk. This supports the cardiovascular protective role of GLP1-RA in clinical practice.

The Belgian registry on coronary function testing (BELmicro registry): study population and prevalence of coronary vascular dysfunction

Abstract Background Coronary function tests (CFT) play a pivotal role in the diagnosis of coronary vascular dysfunction and in providing patients with tailored therapy. Aims To describe baseline characteristics and prevalence of coronary microvascular dysfunction (CMD) and coronary vasospasm in a real-world population of patients undergoing CFT. Methods The Belgian registry on coronary function testing (BELmicro registry) is a prospective, observational registry that includes 14 centers in Belgium. All patients undergoing clinically indicated CFT were included. Baseline characteristics, CFT data, and clinical outcomes were collected. Results Between October 2021 and September 2023, 449 patients were enrolled. The mean age was 65 ± 10 years, and 47.4% of patients were male. Fifty-nine percent of patients had hypertension, 18.7% diabetes, 69.5% hypercholesterolemia, and 40.1% smoking habit. On coronary angiography, the presence of coronary stenosis ≥ 50% was detected in 20.3% of patients. A microvascular physiology assessment was performed in 95.5% of patients, a vasoreactivity test in 28.5%, and both in 24.0%. CMD was diagnosed in 23.6% of patients. Definite epicardial vasospasm was diagnosed in 27.3% of patients, and microvascular spasm in 14.1%. The rates of severe complications were 0.7% for the microvascular physiology assessment and 0% for the vasoreactivity test. Conclusion Participants in the BELmicro registry represent a real-world population of patients, characterized by a high burden of cardiovascular risk factors. Both CMD and coronary vasospasm were frequent. CFT in daily clinical practice was feasible with a low rate of complications.Visual summaryScatter plot of measurements

One- and five-year mortality according to first use of ticagrelor or clopidogrel at the acute stage of myocardial infarction in elderly patients: the FAST-MI 2015 registry

Abstract Background Guidelines recommend ticagrelor over clopidogrel in patients with AMI, irrespective of their age. The PLATO trial, which showed lower mortality with ticagrelor, included only few very elderly patients. Purpose To analyze one- and 5-year outcomes according to use of ticagrelor vs clopidogrel as first P2Y12-inhibitor at the acute stage of AMI, in real-life conditions in patients aged ≥80 years. Methods FAST-MI 2015 included consecutive patients with AMI in 204 centers throughout France. This analysis focused on patients ≥ 80 years of age, in whom the first P2Y12-inhibitor used was either clopidogrel or ticagrelor. Both Cox time-dependent logistic regression and propensity score (PS) matching were used. Results Among 5,291 patients, 995 (19%) were aged ≥ 80 years, of whom 721 (72%) met the inclusion criteria. Mean age was 86 ± 4 years for patients receiving clopidogrel and 84±3 for those receiving ticagrelor, 54% and 52% respectively were women, and 37% vs 54% had STEMI. Using Cox time-dependent regression, the HR (95%CI) for use of ticagrelor vs clopidogrel first was 1.11 (0.75-1.67), P=0.59 for one-year death and 0.61 (0.43-0.86), P=0.004 for death from one to 5 years. After PS matching, the two cohorts (N=231 each) were well balanced; one-year mortality was similar for the 2 medications, while 5-year survival was higher for those receiving ticagrelor first (Figure). Conclusion In this real-world population of elderly patients (mean age 85 years) with AMI, the use of ticagrelor as the first P2Y12-inhibitor was associated with similar survival at one year and improved survival at 5 years, compared with clopidogrel. The diverging one- and 5-year results suggest the possibility of unmeasured confounders. Further research is needed in older patients.Kaplan-Meir curves: survival at 5-years

Transcatheter Valve Repair for TricuspidRegurgitation: 1-Year Results from a Large European Real-World Registry.

Tricuspid valve transcatheter edge-to-edge repair has emerged as a valuable treatment option for patients with severe tricuspid regurgitation (TR). This study aims to investigate the safety and effectiveness of the PASCAL transcatheter valve repair system in treating severe TR in a real-world patient population. The PASTE (PASCAL for Tricuspid Regurgitation-a European registry) study is an investigator-initiated, multicenter, retrospective, and prospective observational cohort analysis conducted across 16 European heart valve centers including consecutive patients treated with the PASCAL transcatheter valve repair system from February 2019 to November 2023. Echocardiographic assessments were performed at baseline, discharge, and follow-up, and were subjected to centralized analysis. The study included 1,059 high-risk patients (mean age 79 ± 9 years; 53% female; TRI-SCORE risk 23% ± 18%; 87% NYHA functional class III/IV) with multiple comorbidities. Severe or higher graded TR was observed in 96% of patients. Intraprocedural success according to Tricuspid Valve Academic Research Consortium criteria was achieved in 85%, and TR reduced to ≤moderate in 87%. Independent predictors for a postprocedure residual TR of >moderate were coaptation gaps≥8mm (OR: 1.67; 95%CI: 1.03-2.72; P=0.038), tenting height≥10mm (OR: 2.18; CI: 1.30-3.65; P=0.003), the presence of a transvalvular lead (OR: 1.91; 95% CI: 1.19-3.05; P=0.007), right ventricular dilatation >42mm (OR: 3.35; 95% CI: 1.37-9.1; P=0.009) and massive/torrential TR at baseline (OR: 4.59; 95% CI:2.35-8.96; P< 0.001). At 1 year, 83% of patients showed ≤moderate TR. Significant clinical improvements included enhanced NYHA functional class (66% class I/II vs 17% at baseline; P< 0.001). Patients treated with the first-generation PASCAL system (n = 570) and with the new PASCAL Precision system (n = 489) had similar clinical profiles and TR severity at baseline. However, the Precision cohort showed greater TR reduction to trace/mild (63% vs 49%; P< 0.001), shorter procedure times (median 93minutes [Q1-Q3: 69-130 minutes] vs 120minutes [Q1-Q3: 82-165 minutes]; P< 0.001), and higher clinical success rates according to the Tricuspid Valve Academic Research Consortium at 30days and 1 year (87% vs 81% [P=0.021] and 56% vs 50% [P=0.044], respectively). Higher center experience (≥21 patients/year) resulted in higher intraprocedural and clinical success. The PASCAL system effectively treats severe TR in high-risk patients, offering sustained TR reduction and significant clinical improvements at 1-year follow-up. (PASCAL for Tricuspid Regurgitation-a European registry [PASTE]; NCT05328284).

Predictors of response to venetoclax and therapeutic potential of CDK7 inhibition in multiple myeloma

AbstractVenetoclax, a selective BCL2 inhibitor, has emerged as a promising therapeutic agent for multiple myeloma (MM), particularly in patients harboring the t(11;14) translocation. In this study, we set out to identify markers of sensitivity and resistance to venetoclax in a real-world patient population, aiming to facilitate the development of personalized therapeutic strategies. Through the analysis of RNA-seq data from relapsed/refractory patients treated with venetoclax, either as a single agent or in combination with other drugs, we unveiled a novel 6-gene signature that significantly stratified patients into risk groups for relapse and further validated its clinical relevance in 2 independent clinical and ex vivo data sets. Our analysis also highlighted the negative impact of chromosome 1q gain, which harbors the MCL1 gene, on progression-free survival, even in t(11;14)-positive patients. Encouraged by the well-documented role of MCL1 in resistance to venetoclax in various malignancies and the prognostic importance of the BCL2/MCL1 ratio in our cohort, we explored Cyclin-Dependent Kinase 7 (CDK7) inhibition as a potential strategy to overcome venetoclax resistance. In vitro experiments demonstrated that CRISPR-Cas9–mediated CDK7 depletion led to decreased MCL1 levels, enhancing the sensitivity of MM cells to venetoclax. Moreover, the combination of the CDK7 inhibitor THZ1 with venetoclax markedly induced cell death in venetoclax-resistant MM cells harboring 1q gain, thus offering a rational therapeutic approach, particularly for patients with this aberration. Overall, these findings provide important insights for optimizing venetoclax-based therapeutic strategies in MM.

S1305 TNFi Cyclers vs MOA Switchers in a Real-World Population of TNFi-Experienced Patients With Ulcerative Colitis: A Propensity Score Adjusted Analysis

S1305 TNFi Cyclers vs MOA Switchers in a Real-World Population of TNFi-Experienced Patients With Ulcerative Colitis: A Propensity Score Adjusted Analysis

The Belgian Registry on Coronary Function Testing (BELmicro Registry): Study Population, Prevalence of Coronary Vascular Dysfunction, and Procedural Safety

Coronary function testing (CFT) plays a pivotal role in the diagnosis of coronary vascular dysfunction and providing patients with tailored therapy. The Belgian registry on CFT (BELmicro registry) is a prospective, observational, multicenter registry including 14 centers in Belgium. All patients who underwent clinically indicated CFT were included in the registry. Baseline characteristics, CFT data, and clinical outcomes were collected. This analysis aimed to describe the baseline characteristics of a real-world population of patients who underwent CFT, evaluate the prevalence of coronary vascular dysfunction, and assess the safety of CFT in daily clinical practice. Between October 2021 and September 2023, 449 patients were enrolled. The mean age was 65 ± 10 years, and 47.4% of patients were men. A total of 59% of patients had hypertension, 18.7% had diabetes, 69.5% had hypercholesterolemia, and 40.1% had a smoking habit. Angina and nonobstructive coronary arteries (ANOCAs) were identified in 85.1% of the patients. Microvascular physiology assessment was performed in 95.5% of patients, vasoreactivity test in 28.5%, and both in 24.0%. coronary microvascular dysfunction was diagnosed in 23.4% of patients with ANOCA, epicardial vasospasm in 26.3%, and microvascular spasm in 14.9%. Rates of major complications were 0.7% for microvascular physiology assessment and 0% for vasoreactivity test. In conclusion, participants in the BELmicro registry represented a real-world population of patients, characterized by a high burden of cardiovascular risk factors. Coronary microvascular dysfunction and coronary vasospasm were frequent in patients with ANOCA. Performing CFT in daily clinical practice was feasible, with a low rate of complications.

Real-world dosing patterns of regorafenib for patients with metastatic colorectal cancer in Spain: the RE-SEARCH study.

To describe the dosing patterns of regorafenib in a real-world population of patients with metastatic colorectal cancer (mCRC) in a routine clinical practice setting in Spain, focusing on the starting dose of regorafenib. An observational, retrospective, multicenter study that included patients ≥ 18years old who had histologically documented mCRC and who had initiated treatment with regorafenib since January 2017. Post hoc categorization of dosing patterns revealed the following: initial dose < 160mg and dose escalation, initial dose < 160mg and maintenance, initial dose equal to 160mg and maintenance, and initial dose equal to 160mg and dose reduction. Most patients (152/241, 63.8%) initiated treatment with regorafenib at doses < 160mg. There was large variation in the starting dose of regorafenib over time: in 2017, most patients (59%) initiated regorafenib at a dose of 160mg, this proportion decreased to 6% in 2021. There were no significant differences in the median progression-free survival according to the regorafenib dose patterns during the first two cycles. The proportion of patients who reported at least one adverse event (AE), had a grade 3-4 AE or had an AE leading to dose reduction was greater in the group of patients who received an initial dose equal to 160 and reduction. Our results indicate that physicians in Spain have gradually adopted a dose-escalation approach during cycle 1, which is a common practice for starting treatment with a reduced dose (< 160mg/day), a strategy that seems to improve tolerability while maintaining efficacy. Not applicable.

Temporal Association Between Atrial Fibrillation Burden in Cardiac Implantable Electronic Devices and the Risk of Heart Failure Hospitalization.

Atrial fibrillation (AF) events in cardiac implantable electronic devices (CIEDs) are temporally associated with stroke risk. This study explores temporal differences in AF burden associated with HF hospitalization risk in patients with CIEDs. Patients with HF events from the Optum de-identified Electronic Health Records from 2007 to 2021 and 120 days of preceding CIED-derived rhythm data from a linked manufacturer's data warehouse were included. AF burden ≥5.5 h/d was defined as an AF event. The AF event burden in the case period (days 1-30 immediately before the HF event) was considered temporally associated with the HF event and compared with the AF event burden in a temporally dissociated control period (days 91-120 before the HF event). The odds ratio for temporally associated HF events and the odds ratio associated with poorly rate-controlled AF (>110 bpm) were calculated. In total, 7257 HF events with prerequisite CIED data were included; 957 (13.2%) patients had AF events recorded only in either their case (763 [10.5%]) or control (194 [2.7%]) periods, but not both. The odds ratio for a temporally associated HF event was 3.93 (95% CI, 3.36-4.60). This was greater for an HF event with a longer stay of >3 days (odds ratio, 4.51 [95% CI, 3.57-5.68]). In patients with AF during both the control and case periods, poor AF rate control during the case period also increased HF event risk (1.78 [95% CI, 1.22-2.61]). In all, 222 of 4759 (5%) patients without AF events before their HF event had an AF event in the 10 days following. In a large real-world population of patients with CIED devices, AF burden was associated with HF hospitalization risk in the subsequent 30 days. The risk is increased with AF and an uncontrolled ventricular rate. Our findings support AF monitoring in CIED algorithms to prevent HF admissions.

Glucagon-like peptide-1 receptor agonist therapy effects on glycemic control and weight in a primary care clinic population.

Glucagon-like peptide-1 receptor agonist (GLP-1a) medications have been shown in randomized controlled trials (RCTs) to have consistent and impressive effectiveness in lowering hemoglobin A1c (HbA1c) and weight, but limited data exist on the efficacy of GLP-1a medications in clinical practice. We studied the association between GLP-1a therapy and changes in weight and HbA1c in a real-world patient population. In this retrospective cohort study of patients seen in a primary care clinic between 2012 and 2021, we examined the change in weight and HbA1c over 12 months in a cohort of patients with at least one prescription for a GLP-1a. Within this cohort, treatment was defined as having ≥2 GLP-1a prescriptions at a therapeutic dosage separated by ≥10 months. The cohort included 693 patients of whom 393 (57%) were treated with GLP-1a therapy. The treatment group had a mean change in body mass index (BMI) of -0.83 kg/m2 (±2.88) compared to -0.70 kg/m2 (±2.99) in the without GLP-1a group (p = 0.57). Treated patients had a mean change in HbA1c of -1.00% (±2.07) compared to -0.83% (±1.92) in the without GLP-1a group (p = 0.27). For treated and without GLP-1a patients, respectively, the proportion of patients with a decrease in BMI was 65 versus 64% (p = 0.86), and the proportion with a decrease in HbA1c was 73 versus 69% (p = 0.28). In clinical practice, GLP-1a therapy was associated with more modest reductions in weight and HbA1c than shown in prior RCTs. As GLP-1a use continues to expand throughout primary care, the real-world impact of this pharmacotherapy will require further evaluation.

External validation of Standardized KELIM and platinum-resistant recurrence scores in patients with advanced epithelial ovarian cancer

BackgroundNeoadjuvant chemotherapy followed by interval debulking surgery is currently a common treatment option for advanced epithelial ovarian cancer (EOC). The Standardized CA-125 ELIMination rate constant K (Std KELIM) and the Platinum Resistant Recurrence (PtRR) Score have been proposed as markers of tumor chemosensitivity. The aim of our study was to validate these tools for predicting platinum sensitivity in a real-world population of patients with advanced EOC treated with neoadjuvant chemotherapy.Experimental designAll patients with advanced EOC treated with neoadjuvant chemotherapy at the Institut Curie between 2000 and 2015 were included. The Std KELIM was calculated with the CA-125 concentrations during the first 100 days of chemotherapy. The predictive value of Std KELIM and PtRR scores for the risk of subsequent PtRR was assessed using receiver operating characteristic (ROC) curve analysis, logistic regression and calibration curve. Kaplan–Meier survival analysis was performed for the treatment-free interval from platinum (TFIp) therapy and overall survival (OS).ResultsStd KELIM data were available for 149 patients. The AUC was 0.67 for PtRR. A low Std KELIM was significantly associated with PtRR (OR = 0.19 (95% CI [0.06, 0.53], p = 0.002)) according to the univariate analysis. The calibration curve of the PtRR showed a slight but significant underestimation (p = 0.02) of the probability of platinum resistance. Favorable Std KELIM (≥ 1) alone and combined with the completeness of surgery were associated with significantly better survival in terms of TFIp and OS.ConclusionsStd KELIM is an early prognostic marker of chemosensitivity in a real-life setting complementary to surgical status. It could help the clinician in the early management of patients by identifying those with a worse prognosis.

Real-world clinical outcomes with fostamatinib for the treatment of refractory chronic immune thrombocytopenia: a single-center experience.

Fostamatinib is a spleen tyrosine kinase inhibitor indicated for the treatment of chronic immune thrombocytopenia (ITP) unresponsive to a previous treatment. Real-world studies evaluating the utilization and effectiveness of fostamatinib outside the context of a clinical trial are lacking. The objective of this analysis was to evaluate the effectiveness of fostamatinib for the treatment of ITP in a real-world cohort. We conducted a single-center, retrospective, observational study to evaluate the effectiveness of fostamatinib for the treatment of ITP. The primary endpoint was durable response as defined by the American Society of Hematology ITP response criteria. Secondary endpoints included overall response rate, time to response, and safety. Subgroup analysis was performed to assess frequency of durable response in key subgroups of patients based on prior therapies. Thirty-one patients treated with fostamatinib for ITP were included in our analysis. Patients had received a median of four prior lines of therapy. Ten patients (32%) achieved a durable response. Most durable responders maintained their response at 24 months ( n = 7; 70%). The median time to response was 9 days. Four patients (13%) discontinued fostamatinib due to an adverse event. Subgroups who had higher rates of durable responses included those who had received two to three prior lines of therapy (40%), splenectomized patients (50%), and those who had not received prior rituximab (55%). Fostamatinib therapy in a real-world population of patients with heavily pretreated ITP led to a durable response in a third of patients, which was maintained for most responders.

Rigid Sternal Fixation and Enhanced Recovery for Opioid-Free Analgesia After Cardiac Surgery

BackgroundWe evaluated the individual contributions of rigid-plate fixation (RPF) and an enhanced recovery protocol (ERP) on postoperative pain, opioid use, and other outcomes after median sternotomy as they were sequentially adopted into practice. MethodsThis single-center, retrospective, case-cohort study compared outcomes between median sternotomy patients (all comers) who underwent operation before implementation of RPF or ERP (“controls”), patients closed with RPF before ERP implementation (“RPF-only”), and patients managed with RPF and ERP during early “RPF+ERP-2020” and late “RPF+ERP-2022” implementation. ResultsThe analysis included 608 median sternotomy patients (mean age, 65.7 ± 10.8 years; 29.6% women). Of those, 59.2% were isolated coronary artery bypass grafting, 7.7% were isolated valve procedures, and the rest were mixed/concomitant procedures. Median in-hospital, postoperative opioid administration was 172.5 morphine milligram equivalents (MMEs) in the control cohort vs 0 MMEs for RPF+ERP-2022 (P < .0001), despite similar or slightly reduced patient-reported pain scores. The proportion of patients discharged directly to home was 66.2% for controls, 79.6% for RPF-only (P = .010), and 93.5% for RPF+ERP-2022 (P < .0001). Median opioids prescribed at discharge were 600 MMEs for controls and 0 for RPF+ERP-2020 and RPF+ERP-2022 (P < .0001). At discharge, 86.7% of RPF-only patients received prescription opioids vs 5% in RPF+ERP-2020 and 4.3% RPF+ERP-2022 (P < .0001). These outcomes occurred without increased readmissions. ConclusionsSystematic implementation of RPF and ERP was associated with a significant and clinically meaningful decrease in opioid use in this large, real-world patient population.

The Multi-Institutional Medullary Thyroid Cancer Collaborative Registry: Can a Rare Tumor Registry Accurately Represent the Real-World Patient Population?

Background: Large population-based registries, such as the Surveillance, Epidemiology and End Results (SEER) Registry, help in the study of rare tumors, including medullary thyroid cancer (MTC), but lack data to understand the natural history of the disease. The Medullary Thyroid Cancer Collaborative Registry (MTCCoRe) is an exhaustive multi-institutional collection of demographic, clinical, and pathological data. To determine the extent to which MTCCoRe represents the real-world MTC population, we compared the characteristics of patients enrolled in MTCCoRe with patients enrolled in population-based cancer registries. Methods: Comparison of demographic and clinical characteristics of MTC patients who were enrolled in MTCCoRe, Texas Cancer Registry (TCR), California Cancer Registry (CCR), and SEER between 1995 and 2018. Results: A total of 1416 patients were identified in MTCCoRe, 329 in TCR, 2105 in CCR, and 3820 in SEER. Percentages of patients 20-54 years in MTCCoRe were 58.0%, 50.2% in TCR, 47.2% in CCR, and 44.8% in SEER (p < 0.0001). About half of the patients were female (55.9% in MTCCoRe, 61.4% in TCR, 59% in CCR, and 57.5% in SEER (p = 0.3). Percentages of Hispanic and Black patients differed among cohorts (10.1% and 3.8% for MTCCoRe, 23.7% and 8.2% for TCR, 24.8% and 4.9% in CCR, and 15.9% and 8.2% for SEER, respectively; p < 0.001). MTCCoRe patients presented with more advanced T and N classifications than patients in the other registries (MTCCoRe, 28.6% T3-4 and 49.4% N1; TCR, 12.7% and 32.2%; CCR, 18.6% and 32.4%; and SEER, 24% and 37.8%; p < 0.0001). Prevalence of M1 disease was 10% in MTCCoRe, 11.9% in TCR, 14.1% in CCR, and 9.5% in SEER (p < 0.0001). In the MTCCoRe, 11.4% underwent systemic therapy (compared with 0.3% in TCR and 5.6% in CCR). Conclusions: The clinicodemographic profile of patients with MTC enrolled in a multi-institutional registry differs from those enrolled in population-based databases, with lower proportions of Hispanic and Black patients but additive data on treatment modalities. Moving forward, MTCCoRe and other registry and clinical trial enrollment efforts should intentionally include underrepresented groups via community engagement techniques, patient stakeholder involvement, and inclusion of languages other than English in study materials to yield more generalizable results and conclusions.

Impact of selexipag maintenance dose on persistence, adherence, and hospitalization in US patients with pulmonary arterial hypertension.

Selexipag is an oral selective agonist of the prostacyclin receptor approved to treat adults with pulmonary arterial hypertension (PAH). Selexipag is initiated at a dose of 200 μg twice daily (bid) and usually titrated up by 200 μg bid weekly (per label) or more slowly (e.g., every other week in real-world clinical practice) to the highest tolerated individualized dose (ID) ranging from 200 to 1600 µg bid. In the Phase 3 GRIPHON trial, selexipag delayed disease progression and reduced risk of PAH-related hospitalization compared with placebo; the effect was consistent across three prespecified ID groups: low (200-400 µg bid), medium (600-1000 µg bid), and high (1200-1600 µg bid). This study evaluated patient outcomes across selexipag dose ranges in real-world practice. Data were analyzed from 1186 US adult patients with PAH on selexipag from the Komodo closed-claims database (2015‒2022). Of these, 634 (53.5%) patients completed titration and reached their selexipag ID (43.8% high ID, 29.8% medium ID, 26.3% low ID). Subsequently, 72.4% of patients in the low ID group had dose adjustments compared with 61.9% (medium ID) and 34.5% (high ID; standardized mean difference 0.63). There were no significant differences in patient outcomes, i,e, persistence (time to discontinuation) and risk of all-cause and PAH-related hospitalization across ID groups. The findings in this diverse, real-world population of patients with PAH reinforced an individualized approach to the dosing scheme to maximize benefit-risk and achieve the highest tolerated dose with selexipag similar to findings from the GRIPHON trial and other studies.

OPTImal PHARMacological therapy for patients with heart failure: Rationale and design of the OPTIPHARM-HF registry.

Patients with heart failure (HF) remain often undertreated for multiple reasons, including treatment inertia, contraindications, and intolerance. The OPTIimal PHARMacological therapy for patients with Heart Failure (OPTIPHARM-HF) registry is designed to evaluate the prevalence of evidence-based medical treatment prescription and titration, as well as the causes of its underuse, in a broad real-world population of consecutive patients with HF across the whole ejection fraction spectrum and among different clinical phenotypes. The OPTIPHARM-HF registry (NCT06192524) is a prospective, multicenter, observational, national study of adult patients with symptomatic HF, as defined by current international guidelines, regardless of ejection fraction. Both outpatients and inpatients with chronic and acute decompensated HF will be recruited. The study will enroll up to 2500 patients with chronic HF at approximately 35 Italian HF centres. Patients will be followed for a maximum duration of 24 months. The primary objective of the OPTIPHARM-HF registry is to assess prescription and adherence to evidence-based guideline-directed medical therapy (GDMT) in patients with HF. The primary outcome is to describe the prevalence of GDMT use according to target guideline recommendation. Secondary objectives include implementation of comorbidity treatment, evaluation of sequence of treatment introduction and up-titration, description of GDMT implementation in the specific HF population, main causes of GDMT underuse, and assessment of cumulative rate of cardiovascular events. The OPTIPHARM-HF registry will provide important implications for improving patient care and adoption of recommended medical therapy into clinical practice among HF patients.

Safety and Efficacy of Dapagliflozin in Patients with Heart Failure with Reduced Ejection Fraction: Multicentre Retrospective Study on Echocardiographic Parameters and Biomarkers of Heart Congestion.

Objectives: Dapagliflozin has shown efficacy in clinical trials in patients with heart failure and reduced ejection fraction (HFrEF). However, real-world data on its use and outcomes in routine clinical practice are limited. We aimed to evaluate the utilisation and safety profile of dapagliflozin in a real-world population of HFrEF patients within the Marche region. Methods: Nine cardiology departments within the Marche region retrospectively included HFrEF patients who were initiated on dapagliflozin therapy in an outpatient setting. Data on medical history, comorbidities, echocardiographic parameters, and laboratory tests were collected at baseline and after 6 months. Telephone follow-up interviews were conducted at 1 and 3 months to assess adverse events. We defined the composite endpoint score as meeting at least 50% of four objective measures of improvement among: weight loss, NYHA decrease, ≥50% Natriuretic peptides (NP) decrease, and guideline/directed medical therapy (GDMT) up titration. Results: We included 95 HFrEF patients aged 66 ± 12 years, 82% were men, 48% had ischemic heart disease, and 20% had diabetes. At six months, glomerular filtration rate declined (p = 0.03) and natriuretic peptides levels decreased, on average, by 23% (p < 0.001). Echocardiographic measurements revealed a decrease in pulmonary artery pressure (p < 0.001) and E/e' (p < 0.001). In terms of drug therapy, furosemide dosage decreased (p = 0.001), and the percentage of the target dose achieved for angiotensin receptor-neprilysin inhibitors increased (p = 0.003). By multivariable Cox regression, after adjustment for age, sex, the presence of diabetes/prediabetes, and HF duration, higher baseline Hb concentrations (HR 1.347, 95% CI 1.038-1.746, p = 0.025), and eGFR levels (HR 1.016, 95% CI 1.000-1.033, p = 0.46). Conclusions: In a real-life HFrEF population, dapagliflozin therapy is safe and well-tolerated, improves echocardiographic parameters and biomarkers of congestion, and can also facilitate the titration of drugs with a prognostic impact.

Increase in blood pressure in patients with metastatic kidney cancer treated with combination checkpoint inhibitor and vascular endothelial growth factor receptor tyrosine kinase inhibitor therapy.

e24128 Background: The combination therapy of an immune checkpoint inhibitor (ICI) with a vascular endothelial growth factor receptor tyrosine kinase inhibitor (VEGFR-TKI) is considered a first line treatment option for patients with metastatic clear cell renal cell carcinoma (ccRCC). TKI-induced hypertension is a well-known potential side effect with VEGFR-TKIs however little is known about the real-world increase in systolic blood pressure (SBP) and diastolic blood pressure (DBP) in patients with and without underlying hypertension treated with this combination therapy. Methods: A retrospective study was performed that included patients with metastatic ccRCC who were treated at the University of Florida Health Cancer Center between June 2019 and September 2022 who received treatment with the combination of an ICI and VEGFR-TKI. The data collected included history of hypertension, patients use of anti-hypertensive therapy at baseline, SBP and DBP prior to initiation of therapy and at approximately one month after initiation of treatment. Results: We identified a total of 29 patients who met the inclusion criteria for our study. The median age was 68 years old (IQR 61-72) while 25 patients (86%) were male and 4 (14%) were females. There were 27 patients (93%) who were treated with axitinib with pembrolizumab, while 1 (3%) was treated with cabozantinib with nivolumab, and 1 (3%) was treated with lenvatinib with pembrolizumab. Out of the 29 patients, 11 (38%) did not have hypertension prior to therapy while 18 (62%) did have baseline hypertension and were receiving at least one anti-hypertensive treatment. In those patients without baseline hypertension, the median baseline SBP was 113 and the median SBP after one month of treatment was 144 (p = 0.01). Conversely, those patients with baseline hypertension, the median baseline SBP was 122 and median SBP after one month of treatment was 148 (p = 0.003). In those without hypertension at baseline, the mean SBP increase after one month was 27.3% while in those with baseline hypertension the mean increase in SBP of 17.0%. Conclusions: Our study demonstrates that in a real-world population of patients with metastatic ccRCC there is a statistically significant elevation of both SBP and DBP when treated with the combination of an ICI and VEGFR-TKI and that in those patients without baseline hypertension and not on anti-hypertensive therapy at baseline, there is a more pronounced increase in blood pressure. This data should reinforce the need to have close monitoring of SBP and DBP during therapy, regardless of whether the patient has underlying hypertension or not, and may help guide anti-hypertensive therapy during kidney cancer treatment.