Guideline-recommended Therapy Research Articles

Trends in Medical and Device Therapies Following Incident Heart Failure in Denmark during 1996-2019: A Nationwide Register-Based Follow-Up Study.

Introduction: Data on temporal trends in guideline-based medical and device therapies in real-world chronic heart failure (HF) patients are lacking. Methods: Register-based nationwide follow-ups of temporal trends in characteristics, guideline-recommended therapies, one-year all-cause mortality, and HF rehospitalizations in incident HF patients in Denmark during 1996-2019. Results: Among 291,720 incident HF patients, the age at the onset of HF was stable over time. While initially fairly equal, the sex distribution markedly changed over time with more incidents occurring in men overall. Hypertension and diabetes increased significantly over time, while other comorbidities remained stable. Between 1996 and 2019, significant increases in angiotensin-converting enzyme inhibitor and angiotensin II-receptor blocker (ACEi/ARB) therapy (38.2% to 69.9%), beta-blocker therapy (15.5% to 70.6%), and mineralocorticoid receptor antagonist (MRA) therapy (11.8% to 34.5%) were seen. Angiotensin receptor-neprilysin inhibitor (ARNI) and sodium-glucose cotransporter-2 inhibitors (SGLT2i) were introduced in the middle of the past decade, with minor increases but overall low uses: ARNI (2015: 0.1% vs. 2019: 3.9%) and SGLT2i (2012: <0.1% vs. 2019: 3.9%). Between 1999 and 2019, implantable cardioverter-defibrillator (ICD) use increased significantly: 0.1% to 3-4%. Cardiac resynchronization therapy (CRT) use similarly increased between 2000 and 2019: 0.2% to 2.3%. Between 1996 and 2019, one-year all-cause mortality decreased significantly: 34.6% to 20.9%, as did HF rehospitalizations (6% to 1.3%). Conclusions: Among 291,720 incident HF patients in Denmark during 1996-2019, significant increases in the use of ACEi/ARB, beta-blockers, MRAs, and devices were seen, with concurrent significant decreases in the one-year all-cause mortality and HF rehospitalization rates. The use of CRT, ARNI, and SGLT2i remained low, and MRAs were relatively underutilized, thereby representing future targets to potentially further improve HF prognoses.

Chronic remote ischemic conditioning treatment in patients with chronic stable angina (EARLY-MYO-CSA): a randomized, controlled proof-of-concept trial

BackgroundChronic remote ischemic conditioning (CRIC) has been shown to improve myocardial ischemia in experimental animal studies; however, its effectiveness in patients with chronic stable angina (CSA) has not been investigated. We conducted a proof-of-concept study to investigate the efficacy and safety of a six-month CRIC treatment in patients with CSA.MethodsThe EARLY-MYO-CSA trial was a prospective, randomized, controlled trial evaluating the CRIC treatment in patients with CSA with persistent angina pectoris despite receiving ≥ 3-month guideline-recommended optimal medical therapy. The CRIC and control groups received CRIC (at 200 mmHg) or sham CRIC (at 60 mmHg) intervention for 6 months, respectively. The primary endpoint was the 6-month change of myocardial flow reserve (MFR) on single-photon emission computed tomography. The secondary endpoints were changes in rest and stress myocardial blood flow (MBF), angina severity according to the Canadian Cardiovascular Society (CCS) classification, the Seattle Angina Questionnaire (SAQ), and a 6-min walk test (6-MWT).ResultsAmong 220 randomized CSA patients, 208 (105 in the CRIC group, and 103 in the control group) completed the treatment and endpoint assessments. The mean change in MFR was significantly greater in the CRIC group than in the control group (0.27 ± 0.38 vs. − 0.04 ± 0.25; P < 0.001). MFR increased from 1.33 ± 0.48 at baseline to 1.61 ± 0.53 (P < 0.001) in the CRIC group; however, a similar increase was not seen in the control group (1.35 ± 0.45 at baseline and 1.31 ± 0.44 at follow-up, P = 0.757). CRIC treatment, when compared with controls, demonstrated improvements in angina symptoms assessed by CCS classification (60.0% vs. 14.6%, P < 0.001), all SAQ dimensions scores (P < 0.001), and 6-MWT distances (440 [400–523] vs. 420 [330–475] m, P = 0.016). The incidence of major adverse cardiovascular events was similar between the groups.ConclusionsCSA patients benefit from 6-month CRIC treatment with improvements in MFR, angina symptoms, and exercise performance. This treatment is well-tolerated and can be recommended for symptom relief in this clinical population.Trial registration[chictr.org.cn], identifier [ChiCTR2000038649].

Circulating soluble IL-6 receptor associates with plaque inflammation but not with atherosclerosis severity and cardiovascular risk

BackgroundThe residual cardiovascular risk in subjects receiving guideline-recommended therapy is related to persistent vascular inflammation and IL-6 represents a target for its treatment. IL-6 binds to receptors on leukocytes and hepatocytes and/or by forming complexes with soluble IL-6 receptors (sIL-6R) binding to gp130 which is present on all cells. Here we aimed to estimate the associations of these two pathways with risk of cardiovascular disease (CVD). MethodsIL-6 and sIL-6R were analyzed using the proximity extension assay. Baseline plasma samples were obtained from participants in the prospective Malmö Diet and Cancer (MDC) study (n = 4661), the SUMMIT VIP study (n = 1438) and the Carotid Plaque Imaging Project (CPIP, n = 285). Incident clinical events were obtained through national registers. Plaques removed at surgery were analyzed by immunohistochemistry and biochemical methods. ResultsDuring 23.1 ± 7.0 years follow-up, 575 subjects in the MDC cohort suffered a first myocardial infarction. Subjects in the highest tertile of IL-6 had an increased risk compared to the lowest tertile (HR and 95% CI 2.60 [2.08–3.25]). High plasma IL-6 was also associated with more atherosclerosis, increased arterial stiffness, and impaired endothelial function in SUMMIT VIP, but IL-6 was only weakly associated with plaque inflammation in CPIP. sIL-6R showed no independent association with risk of myocardial infarction, atherosclerosis severity or vascular function, but was associated with plaque inflammation. ConclusionsOur findings show that sIL-6R is a poor marker of CVD risk and associated vascular changes. However, the observation that sIL-6R reflects plaque inflammation highlights the complexity of the role of IL-6 in CVD.

Dual Endothelin Antagonism with Aprocitentan as a Novel Therapeutic Approach for Resistant Hypertension.

PURPOSEOF REVIEW: Resistant hypertension (RH) defined as uncontrolled blood pressure despite the use of a combination of a renin-angiotensin system blocker, a calcium channel blocker, and a diuretic at maximally tolerated doses is associated with a substantially increased risk of cardiovascular and renal events. Despite targeting relevant pathophysiological pathways contributing to elevated blood pressure, approximately 10-15% of hypertensive patients remain above recommended blood pressure targets. Further optimization of blood pressure control is particularly challenging in patient populations who frequently present with RH such as elderly and patients with chronic kidney disease, due to the unfavorable safety profile of the recommended fourth-line therapy with mineralocorticoid receptor antagonists. This review explores the potential role of endothelin antagonists as an alternative fourth-line therapy. RECENT FINDINGS: Despite the well-described role of the endothelin pathway in the pathogenesis of hypertension, it is currently not targeted therapeutically. Recently however, main outcome data from the PRECISION study, a randomized placebo-controlled phase 3 trial, in patients with RH on guideline-recommended standardized single-pill background therapy convincingly demonstrated the safety and blood pressure-lowering efficacy of the dual endothelin antagonist Aprocitentan. Findings from the phase 3 PRECISION study could signify a turning point in the utilization of endothelin receptor antagonists as a standard treatment for patients with RH.

ASO Visual Abstract: Impact of Adherence to Operative Standards and Stage-Specific Guideline-Recommended Therapy in Non-metastatic Pancreatic Adenocarcinoma.

ASO Visual Abstract: Impact of Adherence to Operative Standards and Stage-Specific Guideline-Recommended Therapy in Non-metastatic Pancreatic Adenocarcinoma.

Gaps in Guideline-Based Lipid-Lowering Therapy for Secondary Prevention in the United States: A Retrospective Cohort Study of 322 153 Patients.

Many patients with atherosclerotic cardiovascular disease (ASCVD) are not on guideline-recommended statin therapy. We evaluated utilization of statins and other lipid-lowering therapy (LLT), and changes in low-density lipoprotein cholesterol (LDL-C), among patients with ASCVD over a 1-year period. LLT and LDL-C levels at the first outpatient visit (January 1, 2017-December 31, 2018) and 1-year follow-up were evaluated using data from Cerner Real-World Data, an electronic health record-derived data set from 92 US health systems. Logistic regression was used to evaluate factors associated with high-intensity statin use. We identified 322 153 patients with ASCVD (median age 69 years, 58.8% men, 81.8% White). Overall, 76.1% of patients were on statins, with only 39.4% on high-intensity statins. Men were more likely to receive high-intensity statins than women (multivariable-adjusted odds ratio, 1.34 [95% CI, 1.30-1.38]). Increasing age was associated with lower odds of statin use (odds ratio, 0.79 per 5-year increase at 60 years [95% CI, 0.78-0.81]). Patients with peripheral artery disease (odds ratio, 0.40 [95% CI, 0.37-0.42]) and cerebrovascular disease (odds ratio, 0.75 [95% CI, 0.70-0.80]) had lower odds of using high-intensity statins than those with coronary artery disease. At baseline, most patients (61.3%) had elevated LDL-C (≥70 mg/dL), including 59.8% of those on low/moderate-intensity statins and 76.1% on no statin; only 45.3% achieved an LDL-C <70 mg/dL at 1 year. Nonstatin LLT use was low (ezetimibe, 4.4%; proprotein convertase subtilisin/kexin type 9 inhibitors, 0.7%). Among patients on no statin or low/moderate-intensity statin at baseline, 14.8% and 13.4%, respectively, were on high-intensity statins at 1 year. Among patients with ASCVD in routine care, high-intensity statins are underutilized, and uptitration and use of nonstatin therapy are uncommon. Women, older adults, and individuals with noncardiac ASCVD are particularly undertreated. Concerted efforts are needed to address therapeutic inertia for lipid management in patients with ASCVD.

Temporal Trends in Infarct Severity Outcomes in ST-Segment-Elevation Myocardial Infarction: A Cardiac Magnetic Resonance Imaging Study.

Background Severity of myocardial tissue injury is a main determinant of morbidity and death related to ST-segment-elevation myocardial infarction (STEMI). Temporal trends of infarct characteristics at the myocardial tissue level have not been described. This study sought to assess temporal trends in infarct characteristics through a comprehensive assessment by cardiac magnetic resonance imaging at a standardized time point early after STEMI. Methods and Results We analyzed patients with STEMI treated with percutaneous coronary intervention at the University Hospital of Innsbruck who underwent cardiac magnetic resonance imaging between 2005 and 2021. The study period was divided into terciles. Myocardial damage characteristics were assessed using a multiparametric cardiac magnetic resonance imaging protocol within the first week after STEMI and compared between groups. A total of 843 patients with STEMI (17% women) with a median age of 57 (interquartile range, 51-66) years were analyzed. While age, sex, and the clinical risk profile expressed as thrombolysis in myocardial infarction risk score were comparable across the study period, there were differences in guideline-recommended therapies. At the same time, there was no significant change in infarct size (P=0.25), microvascular obstruction (P=0.50), and intramyocardial hemorrhage (P=0.34). Left ventricular remodeling indices and left ventricular ejection fraction remained virtually unchanged (all P>0.05). Major adverse cardiovascular events at 4 (interquartile range, 4-5) months were similar between groups (P=0.36). Conclusions In this magnetic resonance imaging study investigating patients with STEMI treated with primary percutaneous coronary intervention over the past 15 years, no change in infarct severity at the myocardial level has been observed. Clinical research on novel therapeutic approaches to reduce myocardial tissue injury should be a priority.

Using Polygenic Risk Scores for Prioritizing Individuals at Greatest Need of a Cardiovascular Disease Risk Assessment.

Background The aim of this study was to provide quantitative evidence of the use of polygenic risk scores for systematically identifying individuals for invitation for full formal cardiovascular disease (CVD) risk assessment. Methods and Results A total of 108 685 participants aged 40 to 69 years, with measured biomarkers, linked primary care records, and genetic data in UK Biobank were used for model derivation and population health modeling. Prioritization tools using age, polygenic risk scores for coronary artery disease and stroke, and conventional risk factors for CVD available within longitudinal primary care records were derived using sex-specific Cox models. We modeled the implications of initiating guideline-recommended statin therapy after prioritizing individuals for invitation to a formal CVD risk assessment. If primary care records were used to prioritize individuals for formal risk assessment using age- and sex-specific thresholds corresponding to 5% false-negative rates, then the numbers of men and women needed to be screened to prevent 1 CVD event are 149 and 280, respectively. In contrast, adding polygenic risk scores to both prioritization and formal assessments, and selecting thresholds to capture the same number of events, resulted in a number needed to screen of 116 for men and 180 for women. Conclusions Using both polygenic risk scores and primary care records to prioritize individuals at highest risk of a CVD event for a formal CVD risk assessment can efficiently prioritize those who need interventions the most than using primary care records alone. This could lead to better allocation of resources by reducing the number of risk assessments in primary care while still preventing the same number of CVD events.

Switching from Dual Antiplatelet Therapy with Aspirin Plus a P2Y12 Inhibitor to Dual Pathway Inhibition with Aspirin Plus Vascular-Dose Rivaroxaban: The Switching Anti-Platelet and Anti-Coagulant Therapy (SWAP-AC) Study.

To date, there are no data on switching to dual pathway inhibition (DPI) patients who have completed a guideline-recommended dual antiplatelet therapy (DAPT) regimen. To assess the feasibility of switching from DAPT to DPI and to compare the pharmacodynamic (PD) profiles of these treatments. This was a prospective, randomized, PD study conducted in 90 patients with chronic coronary syndrome (CCS) on DAPT with aspirin (81 mg/qd) plus a P2Y12 inhibitor (clopidogrel [75 mg/qd; n = 30], ticagrelor [90 mg/bid; n = 30], or prasugrel [10 mg/qd; n = 30]). Patients in each cohort were randomized to maintain DAPT or switch to DPI (aspirin 81 mg/qd plus rivaroxaban 2.5 mg/bid). PD assessments included: VerifyNow P2Y12 reaction units; light transmittance aggregometry following stimuli with adenosine diphosphate (ADP), tissue factor (TF), and a combination of collagen, ADP, and TF (maximum platelet aggregation %); thrombin generation (TG). Assays were performed at baseline and 30 days postrandomization. Switching from DAPT to DPI occurred without major side effects. DAPT was associated with enhanced P2Y12 inhibition, while DPI with reduced TG. Platelet-mediated global thrombogenicity (primary endpoint) showed no differences between DAPT and DPI in the ticagrelor (14.5% [0.0-63.0] vs. 20.0% [0.0-70.0]; p = 0.477) and prasugrel (20.0% [0.0-66.0] vs. 4.0% [0.0-70.0]; p = 0.482), but not clopidogrel (27.0% [0.0-68.0] vs. 53.0% [0.0-81.0]; p = 0.011), cohorts. In patients with CCS, switching from different DAPT regimens to DPI was feasible, showing enhanced P2Y12 inhibition with DAPT and reduced TG with DPI, with no differences in platelet-mediated global thrombogenicity between DPI and ticagrelor- and prasugrel-, but not clopidogrel-, based DAPT. http://www. gov Unique Identifier: NCT04006288.

Impact of the SGLT2-inhibitor empagliflozin on inflammatory biomarkers after acute myocardial infarction – a post-hoc analysis of the EMMY trial

BackgroundSGTL2-inhibitors are a cornerstone in the treatment of heart failure, but data on patients with acute myocardial infarction (AMI) is limited. The EMMY trial was the first to show a significant reduction in NTproBNP levels as well as improved cardiac structure and function in post-AMI patients treated with Empagliflozin compared to placebo. However, data on the potential impact of SGLT2-inhibitors on inflammatory biomarkers after AMI are scarce.Materials and methodsThe EMMY trial is an investigator-initiated, multicentre, double-blind, placebo-controlled trial, which enrolled patients after AMI, receiving either 10 mg Empagliflozin once daily or placebo over a period of 26 weeks on top of standard guideline-recommended therapy starting within 72 h after percutaneous coronary intervention. In this post-hoc subgroup analysis of the EMMY trial, we investigated inflammatory biomarkers of 374 patients. The endpoints investigated were the mean change in inflammatory biomarkers such as high-sensitive c-reactive protein (hsCRP), interleukin-6 (IL-6), neutrophils, leukocytes, neutrophile/lymphocyte ratio (NLR) and platelet to lymphocyte ratio (PLR) from baseline to 26 weeks.ResultsBaseline median (interquartile ranges) IL-6 was 17.9 pg/mL (9.0-38.7), hsCRP 18.9 mg/L (11.2–37.1), neutrophil count 7.9 x G/L (6.2–10.1), leukocyte count 10.8 x G/L (9.1–12.8) and neutrophile/lymphocyte ratio (NLR) of 0.74 (0.67–0.80). At week 26, a significant mean reduction in inflammatory biomarkers was observed, being 35.1 ± 3.2% (p < 0.001) for IL-6, 57.4 ± 0.7% (p < 0.001) for hsCRP, 26.1 ± 0.7% (p < 0.001) for neutrophils, 20.5 ± 0.6% (p < 0.001) for leukocytes, 10.22 ± 0.50% (p < 0.001) for NLR, and − 2.53 ± 0.92% for PLR (p = 0.006) with no significant difference between Empagliflozin and placebo treatment.ConclusionTrajectories of inflammatory biomarkers showed a pronounced decline after AMI, but Empagliflozin treatment did not impact this decline indicating no central role in blunted systemic inflammation mediating beneficial effects.

Demonstrating the importance of local culture and susceptibility data: antibiograms from dogs at a veterinary tertiary care center.

To create antibiograms for commonly cultured organisms in a small animal tertiary care hospital following Clinical and Laboratory Standards Institute guidelines and to compare these local resistance patterns to published first-tier antimicrobial recommendations. Urine (n = 429), respiratory (41), and skin (75) isolates cultured from dogs between January 1, 2019, and December 31, 2020, at the Tufts University Foster Hospital for Small Animals. MIC and susceptibility interpretations were recorded for multiple sites for 2 years. Sites with greater than 30 isolates for at least 1 organism were included. Urinary, respiratory, and skin antibiograms were created using Clinical and Laboratory Standards Institute breakpoints and guidelines. Urinary Escherichia coli had a higher susceptibility percentage for amoxicillin-clavulanate (80% [221/275]) than amoxicillin alone (64% [175/275]). Respiratory E coli were greater than 80% susceptible to only 2 antimicrobials (imipenem, amikacin). Of skin Staphylococcus pseudintermedius isolates, 40% (30/75) were methicillin-resistant and frequently also displayed resistance to non-beta lactam antimicrobials. Susceptibility to recommended first-line antimicrobials varied and was greatest for gram-negative urinary isolates and lowest for methicillin-resistant S pseudintermedius skin isolates and respiratory E coli. Local antibiogram creation identified frequent resistance that may preclude the use of guideline-recommended first-line therapy. High levels of resistance identified in methicillin-resistant S pseudintermedius isolates supports growing concern for methicillin-resistant staphylococci in veterinary patients. This project highlights the need for population-specific resistance profiles to be used in conjunction with national guidelines.

Coronary revascularization for heart failure with coronary artery disease: a systematic review and meta-analysis of randomized trials.

Coronary artery disease (CAD) is a common cause of heart failure (HF). Whether coronary revascularisation improves outcomes in patients with HF receiving guideline-recommended pharmacological therapy (GRPT) remains uncertain; therefore, we conducted a systematic review and meta-analysis of relevant randomized controlled trials (RCTs). We searched in public databases for RCTs published between 1st January 2001 and 22nd November 2022, investigating the effects of coronary revascularisation on morbidity and mortality in patients with chronic HF due to CAD. All-cause mortality was the primary outcome. We included five RCTs that enrolled, altogether, 2,842 patients (most aged <65 years; 85% men; 67% with left ventricular ejection fraction ≤35%). Overall, compared to medical therapy alone, coronary revascularisation was associated with a lower risk of all-cause mortality (HR 0.88 [95% CI, 0.79-0.99]; p=0.0278) and cardiovascular mortality (HR 0.80 [95% CI, 0.70-0.93]; p=0.0024) but not the composite of hospitalisation for HF or all-cause mortality (HR 0.87 [95% CI, 0.74-1.01]; p=0.0728). There were insufficient data to show whether the effect of CABG or PCI were similar or differed. For patients with chronic HF and CAD enrolled in RCTs, the effect of coronary revascularization on all-cause mortality was statistically significant but neither substantial (HR 0.88) nor robust (upper 95% CI close to 1.0). RCTs were not blinded, which may bias reporting of the cause-specific reasons for hospitalization and mortality. Further trials are required to determine which patients with HF and CAD obtain a substantial benefit from coronary revascularization by either CABG or PCI. This article is protected by copyright. All rights reserved.

Impact of an immersive, interactive medical education initiative on guideline-based retinal disease management knowledge/competence and effectual practice change

BackgroundRetinal diseases, including wet or dry age-related macular degeneration, diabetic macular edema, and diabetic retinopathy (DR), are underdiagnosed and undertreated in the United States. Clinical trials support the effectiveness of anti-vascular endothelial growth factor (anti-VEGF) therapies for several retinal conditions, but real-world data suggest underuse by clinicians, resulting in patients experiencing poorer visual outcomes over time. Continuing education (CE) has demonstrated effectiveness at changing practice behaviors, but more research is needed to understand whether CE can help address diagnostic and treatment gaps.MethodsThis test and control matched pair analysis examined pre-/post-test knowledge of retinal diseases and guideline-based screening and intervention among 10,786 healthcare practitioners (i.e., retina specialists, ophthalmologists, optometrists, primary care providers, diabetes educators, pharmacists/managed care specialists, and other healthcare providers, such as registered nurses, nurse practitioners, and physician assistants) who participated in a modular, interactive CE initiative. An additional medical claims analysis provided data on practice change, evaluating use of VEGF-A inhibitors among retina specialist and ophthalmologist learners (n = 7,827) pre-/post-education, compared to a matched control group of non-learners. Outcomes were pre-/post-test change in knowledge/competence and clinical change in application of anti-VEGF therapy, as identified by the medical claims analysis.ResultsLearners significantly improved knowledge/competence scores on early identification and treatment, identifying patients who could benefit from anti-VEGF agents, using guideline-recommended care, recognizing the importance of screening and referral, and recognizing the importance of early detection and care for DR (all P-values = 0.003 to 0.004). Compared with matched controls, learners’ incremental total injections for anti-VEGF agents for retinal conditions increased more after the CE intervention (P < 0.001); specifically, there were 18,513 more (new) anti-VEGF injections prescribed versus non-learners (P < 0.001).ConclusionsThis modular, interactive, immersive CE initiative resulted in significant knowledge/competence gains among retinal disease care providers and changes in practice-related treatment behaviors (i.e., appropriate consideration and greater incorporation of guideline-recommended anti-VEGF therapies) among participating ophthalmologists and retina specialists compared to matched controls. Future studies will utilize medical claims data to show longitudinal impact of this CE initiative on treatment behavior among specialists and impact on diagnosis and referral rates among optometrists and primary care providers who participate in future programming.

Impact of Adherence to Operative Standards and Stage-Specific Guideline-Recommended Therapy in Nonmetastatic Pancreatic Adenocarcinoma.

Achieving optimal surgical outcomes in pancreatic adenocarcinoma requires a combination of both curative-intent resection to oncologic standards and stage-specific neoadjuvant or adjuvant therapy. This investigation sought to examine factors associated with receipt of standard-adherent surgery (SAS) and guideline-recommended therapy (GRT) and determine the impact of compliance on patient survival. From the 2006-2016 National Cancer Database, 21,304 patients underwent resection for nonmetastatic pancreatic adenocarcinoma. SAS was defined as pancreatic resection with negative margins and ≥15 lymph nodes examined. Stage-specific GRT was defined by current National Comprehensive Cancer Network guidelines. Multivariable models were used to determine predictors of adherence to SAS and GRT and prognostic impact on overall survival. Overall, SAS was achieved in 39% and GRT in 65% of patients, but only 30% received both SAS and GRT. Increasing age, minority race, uninsured status, and greater comorbidities were associated with a decreased odds of receiving both SAS and GRT (all p<0.05). SAS (HR 0.79; CI 0.76-0.81; p<0.001) and GRT (HR 0.67; CI 0.65-0.69; p<0.001) were each independently associated with a survival advantage. Receipt of both SAS and GRT was associated with significant improvement in median OS compared with receiving neither (2.2years vs 1.1 years; p<0.001) which was independently associated with a 78% increased risk of death (HR 1.78; CI 1.70-1.86; p<0.001). Despite survival benefits associated with adherence to operative standards and receipt of guideline-recommended therapy, compliance remains poor. Future efforts must be directed toward improved education and implementation efforts around both operative standards and therapy guidelines.

#2976 CHRONIC KIDNEY DISEASE WITH COMORBIDITY IN PRIMARY CARE: CARDIORENAL TREATMENT, QUALITY OF CARE AND PROGNOSIS

Abstract Background and Aims Diabetes, heart failure, hypertension and cardiovascular disease are common in primary care, and frequently coexist with impaired kidney function (CKD), further increasing risk of cardiovascular- and renal events as well as premature death. These comorbidities therefore call for more complex treatment regimens and monitoring. Our aim was to describe the prevalence, management, and prognosis of individuals with CKD and additional comorbidity in a large primary care cohort. Method Individuals were included from the Copenhagen Primary Care Laboratory (CopLab) Database, which contains 112 million biochemistry results from persons followed in primary care between 2000 and 2015 and divided into three groups based on (CKD-EPI) eGFR (&amp;gt;60 ml/min, 30-59 ml/min and &amp;lt;30 ml/min) with or without comorbidity in the form of diabetes or heart failure. We included all individuals with at least two measurements of creatinine. The date of the second measurement of creatinine was considered index date (baseline). The database has been combined with pharmacological data (The Danish National Prescription Registry), outpatient clinic visits and hospitalizations (The Danish National Patient Registry - NPR), and mortality information (The Danish Civil Registration System). Heart Failure was defined by ICD-codes in NPR from outpatient clinic visits and hospitalizations and we calculated crude event rates for a range of outcomes according to comorbidity. Diabetes was defined as at least one measurement of plasma or serum glucose ≥11 mmol/l or HbA1c ≥48 mmol/mol in CopLab. We evaluated monitoring of eGFR, albuminuria (UACR) and use of guideline-recommended pharmacological therapy (i.e. RAS-blockers and statins) in each group. Results In the total primary care population of 171,134 individuals of which 63.8% were female, 8.3% had impaired kidney function (eGFR&amp;lt;60ml/min). The median follow-up for the three eGFR groups was 8.4, 4.7 and 2.0 years, respectively. Overall, event rates were higher in individuals with impaired kidney function and comorbidity, i.e. mortality in the group with eGFR&amp;lt;30 ml/min with concurrent heart failure; 42.8 per 100 patient-years (PY). Event rates for ESKD were low in general (0.03 to 0.51 per 100 PY) except for individuals with eGFR&amp;lt;30 ml/min (2.1 to 3.5 per 100 PY). Annual monitoring of eGFR was high in all groups (&amp;gt;90%) with increasing frequency in individuals with impaired kidney function, and measurement of UACR was low in groups with non-diabetic CKD (10-30%). Antihypertensive treatment was frequently prescribed in eGFR &amp;lt;30 ml/min; overall 87.6% and 94.8% with coexisting diabetes and 92.8% with coexisting heart failure. The use of RAS inhibition was more used in diabetes and in heart failure (&amp;gt;50%) but less with low eGFR. Statin therapy was used in approximately 50% of individuals with diabetes, regardless of CKD group, but was used to a much less extent in non-diabetic CKD (20-24%). Conclusion Our data from a large primary care cohort demonstrate a high prevalence of coexisting diabetes and/or heart failure with CKD, increasing the risk for adverse outcomes. The quality of CKD care in general practice may be improved, especially in the non-diabetic population.

Physical Frailty and Use of Guideline-Recommended Drugs in Patients With Heart Failure and Reduced Ejection Fraction.

BACKGROUND Guideline-recommended therapies that improve prognosis remain underused in clinical practice. Physical frailty may lead to underprescription of life-saving therapy. We aimed to investigate the association between physical frailty and the use of evidence-based pharmacological therapy for heart failure with reduced ejection fraction and the impact of this on prognosis. METHODS AND RESULTS The FLAGSHIP (Multicentre Prospective Cohort Study to Develop Frailty-Based Prognostic Criteria for Heart Failure Patients) included patients hospitalized for acute heart failure, and data on physical frailty were collected prospectively. We analyzed 1041 patients with heart failure with reduced ejection fraction (aged 70 years; 73% male) and divided them by physical frailty categories using grip strength, walking speed, Self-Efficacy for Walking-7 score, and Performance Measures for Activities of Daily Living-8 score: categories I (n=371; least frail), II (n=275), III (n=224), and IV (n=171). Overall prescription rates of angiotensin-converting enzyme inhibitors/angiotensin receptor blockers, β-blockers, and mineralocorticoid receptor antagonists were 69.7%, 87.8%, and 51.9%, respectively. The proportion of patients receiving all 3 drugs decreased as physical frailty increased (in category I patients, 40.2%; IV patients, 23.4%; P for trend<0.001). In adjusted analyses, the severity of physical frailty was an independent predictor for nonuse of angiotensin-converting enzyme inhibitors/angiotensin receptor blockers (odds ratio [OR], 1.23 [95% CI, 1.05-1.43] per 1 category increase) and β-blockers (OR, 1.32 [95% CI, 1.06-1.64]), but not mineralocorticoid receptor antagonists (OR, 0.97 [95% CI, 0.84-1.12]). Patients receiving 0 to 1 drug had a higher risk of the composite outcome of all-cause death or heart failure rehospitalization than those treated with 3 drugs in physical frailty categories I and II (hazard ratio [HR], 1.80 [95% CI, 1.08-2.98]) and III and IV (HR, 1.53 [95% CI, 1.01-2.32]) in the multivariate Cox proportional hazard model. CONCLUSIONS Prescription of guideline-recommended therapy decreased as severity of physical frailty increased in heart failure with reduced ejection fraction. Underprescription of guideline-recommended therapy may contribute to the poor prognosis associated with physical frailty.

Reliance of agency-approved and guideline-recommended therapies on surrogate endpoints in triple-negative breast cancer (TNBC).

e13085 Background: Surrogate endpoints, such as progression-free survival (PFS) and event-free survival (EFS), are used for accelerated approval in various cancers, including TNBC. Here we review the use of surrogates and clinical outcomes in determining agency approval and guideline recommendation. Methods: Phase 2/3 TNBC trials and trials including TNBC subgroups reporting hazard ratios (HR) for clinical and surrogate endpoints were identified through a systematic search of LARVOL CLIN, PubMed, and conference proceedings. Trials that only evaluated cytotoxic agents and did not report EFS, PFS and/ or overall survival (OS) HR values were excluded. We performed a descriptive analysis of agency and guideline approvals in relation to therapeutic benefit as measured by surrogate outcomes and OS. Results: 21 TNBC cohorts and 1 pooled analysis studying 17 different targeted therapies for TNBC were included. There are 3 targeted therapies that have agency approval and 7 targeted therapies that are recommended by either the NCCN, EMA and ASCO guidelines. Of the two FDA and EMA-approved therapies, pembrolizumab + chemotherapy (PBL + CHT) showed PFS/EFS benefit for early TNBC and PDL1+ metastatic (m) TNBC but only OS benefit for PDL1+ mTNBC, whereas sacituzumab showed significant benefit for both PFS and OS for mTNBC. Four therapies (olaparib for BRCA+ mTNBC, bevacizumab for early TNBC, talazoparib for BRCA+ mTNBC and PBL + CHT for PD-L1+ mTNBC) are recommended by guidelines without having a significant OS benefit. Conclusions: Surrogate outcomes are heavily relied upon for TNBC guideline recommendation. Despite the need for timely access to novel TNBC therapeutics, clinical outcomes should be followed to ensure benefit once they have been reached. An up-to-date digitized trial results repository would ensure expedient review of clinical endpoints. [Table: see text]

EE295 Patient Financial Burden Following Discontinuation of Oral Pharmacotherapy: An Analysis of Treatment Options for Men with Erectile Dysfunction

Oral pharmacotherapy is considered a first-line management option for erectile dysfunction (ED), yet many men discontinue the therapy, thereby requiring further intervention. Given US healthcare spending concerns, this cost analysis estimated the Medicare patient costs of guideline-recommended non-oral therapies for ED.

Predictors of Ejection Fraction Improvement in Northland Heart Failure Patients

Northland has a disproportionately high burden of cardiovascular disease, including heart failure (HF). Since 2019, there has been an increase in clinical focus on mid and far north HF patients, aiming to understand and improve HF care to this challenging and often comorbid patient group. Clinical data were prospectively collected, between October 2019 and March 2020, on 86 consecutive cardiology clinic patients with heart failure with reduced ejection fraction (HFrEF) in Kaitaia and Bay of Islands hospitals. Table 1 shows cohort demographics.Table 1Patient demographics.Number of patients86Mean age (yr)62% male85% Māori71% diabetic38 Open table in a new tab A total of 42% of patients had a >15% increase in ejection fraction (EF), as show in Figure 1. The strongest predictor of EF improvement was lack of ischaemic heart disease as a cause/contributor to HFrEF (Table 2). Figure 2 shows the uptake of Entresto (sacubitril/valsartan) and empagliflozin over time. The relationship with Entresto use largely reflects the fact that most patients NOT prescribed Entresto had an early significant improvement with other management.Table 2Predictors of EF improvement.EFDecline or no change≤15% increase>15% increasePatients (%)25 (29)25 (29)36 (42)Mean age (yr)616461% Māori727269% male888881Alcohol %402836Ischaemic %283217Non-adherence522Entresto %1008461Empagliflozin %202825Death310 Open table in a new tab Figure 2Use of newer guideline recommended HF therapy for the 86 patientsView Large Image Figure ViewerDownload Hi-res image Download (PPT) There has been a steady increase in used of guideline-recommended HF therapy in Northland rural hospital patients.

Electronic health record (EHR)-based machine learning (ML) to predict disease recurrence after surgical resection of early-stage non-small cell lung cancer (eNSCLC).

6626 Background: Surgical resection (SR) is a guideline-recommended definitive therapy for patients (pts) with eNSCLC. However, 30–50% pts develop disease recurrence (DR) within the first 5 years (yrs) after surgery. ML applied to routinely collected EHR data could facilitate timely identification of pts at risk of DR who would benefit from enhanced surveillance or initial treatment (Tx) intensification. Methods: eNSCLC pts with stage IB-IIIA at the time of SR between Jan 2010 – February 2022 were identified from ConcertAI Patient360 oncology database comprising structured and curated records from US-based EHR. DR was defined as the human-curated earliest advanced/metastatic diagnosis date from SR. Gradient boosting (GB), random forest (RF), and logistic regression (LR) algorithms with 6-fold nested cross-validation were trained and compared to predict the risk of DR or death at 2 yrs from SR. Pts who did not experience DR and were lost to follow-up within 2 yrs from SR were removed. Feature importance was defined using Shapley Additive Explanation (SHAP)-derived odds ratios (OR). Due to low prevalence of DR at 2 yrs, AUPRC was used as performance metric. Pts in the 1st and 4th quartiles of predicted probabilities from XGB model were defined as low-risk vs. high-risk groups. Results: Among 3597 pts, median age was 68.3 yrs (IQR 12.5), 51.8% were female, and 8.6% were Black. 24.4% developed DR within 2 yrs. GB, RF, and LR models had similar ability to predict DR at 2 yrs with mean hold-out set AUPRC of 0.33. In GB model, DR prevalence at 2 yrs was 34% in the high-risk vs. 18% in the low-risk group in hold-out set. N0 stage, T stage &lt; 3, receipt of adjuvant immune checkpoint inhibitor (ICI), and presence of EGFR mutations were protective against DR at 2 yrs, while history of anemia and congestive heart failure (CHF) were risk factors (Table). SHAP revealed a N stage-by-adjuvant therapy and a N stage-by-CHF interaction: benefit from adjuvant chemotherapy (CT) was limited to higher N stages, while adjuvant ICI was beneficial for all N stages. CHF was a risk factor for lower N stages but not for higher N stages. Conclusions: ML applied to structured and unstructuredEHRs identified predictors of risk of DR at 2 yrs after surgery in eNSCLC and may identify high-risk pts who would benefit from enhanced surveillance plans and Tx intensification in the eNSCLC setting. The model indicated favorable outcome from adjuvant targeted therapies in EGFR mutated pts. [Table: see text]