Guideline-recommended Therapy Research Articles

Patient-Reported Reasons for Not Using Primary Prevention Statin Therapy.

Almost half of patients who meet American College of Cardiology/American Heart Association (ACC/AHA) criteria for statin therapy are untreated. We aimed to evaluate patient-reported reasons for not using guideline-recommended statin therapy in a public healthcare system. Achieving this goal is key to addressing gaps in care and reducing preventable cardiovascular morbidity. We surveyed patients who met 2013 ACC/AHA guidelines for statin therapy but were not using statins. The survey probed domains of patient knowledge regarding cardiovascular health and benefits of statins, barriers to use, physician trust, and interest in cardiovascular care. Among 71 patients eligible for guideline-recommended statin therapy but not currently taking statins, 49 (69%) had a high school education or lower, 41 (58%) reported that they were unaware they should be prescribed a statin and 49 (69%) were unaware of the benefits of statins. Almost all patients, 70 (99%), reported caring about their cardiovascular health, 61 (86%) reported that they had a high level of trust in their physician, and 51 (72%) reported a willingness to follow their physician’s advice. Despite interest in cardiovascular health, awareness of benefits of statin therapy was low and knowledge of recommended statin therapy was low. Increasing patients’ awareness of their eligibility through systematic testing and linkage to statin therapy, along with education, may increase statin use among patients recommended for therapy.

Efficacy and Safety of Modified Dual Therapy as the First-line Regimen for the Treatment of Helicobacter pylori Infection: A Meta-Analysis of Randomized Controlled Trials.

In an era of antibiotic resistance, modified dual therapy has been paid much attention because of simple drug composition and low resistance of amoxicillin. However, its eradication rate as a first-line regimen remains controversial. This study is to evaluate the efficacy and safety of modified dual therapy for the initial treatment of Helicobacter pylori (H. pylori) infection compared with mainstream first-line therapies. PubMed, the Cochrane Library, and Embase were searched for randomized clinical trials evaluating the efficacy and safety of modified dual therapy as the initial treatment for H. pylori eradication compared with guideline-recommended first-line therapies. A meta-analysis was conducted using Review Manager 5.3 and dichotomous data were estimated by the risk ratio (RR) with the 95% confidence interval (CI). We also performed subgroup analysis according to control groups and studies with antibiotic susceptibility tests. Eight studies including 1672 patients with H. pylori infection met the selection criteria and were assessed. The meta-analysis demonstrated that modified dual therapy achieved similar efficacy [85.83% vs. 86.77%, RR 0.99 (95% CI, 0.95-1.03), intention-to-treat analysis; 89.53% vs. 90.45%, RR 0.99 (95% CI, 0.96-1.02), per-protocol analysis] and compliance [95.77% vs. 95.56%, RR 1.00 (95% CI, 0.98-1.02)] compared with recommended first-line regimens. In addition, there were no significant differences in comparing the eradication rate of modified dual therapy with clarithromycin triple therapy, bismuth quadruple therapy, and concomitant therapy, respectively. Subgroup analysis based on the studies with antibiotic susceptibility tests also confirmed a similar efficacy. However, modified dual therapy showed fewer adverse effects [8.70% vs. 22.38%, RR 0.39 (95% CI, 0.28-0.54)], with a significant difference (P<0.00001). Modified dual therapy achieved equal efficacy and compliance compared with recommended first-line regimens for H. pylori infection, and generally modified dual therapy showed fewer side effects.

Adherence to and determinants of guideline-recommended biomarker testing and targeted therapy in patients with gastroesophageal adenocarcinoma: Insights from routine practice.

12 Background: Precision oncology has transformed care for patients with advanced HER2+ gastroesophageal adenocarcinoma (GEA), where the addition of anti-HER2 therapy with trastuzumab improves overall survival and is now incorporated into national guidelines. However, little is known about adherence to and determinants of timely HER2 testing and trastuzumab initiation in routine care. Methods: We performed a retrospective study of advanced GEA diagnosed between 1/2011 and 6/2019 in the nationwide Flatiron Health EHR-derived deidentified database. We calculated annual prevalence and identified determinants of timely HER2 testing (defined within 21 days after advanced diagnosis) and timely first-line trastuzumab initiation (defined within 14 days after a HER2+ result). Log binomial regressions estimated adjusted prevalence ratios (PR) comparing timely HER2 testing and trastuzumab initiation by patient and tumor characteristics. Multiple imputation was conducted for missing data. Results: We included 6,479 patients with advanced GEA; 973 were HER2+ of whom 585 (60.1%) initiated trastuzumab. Prevalence of timely HER2 testing increased from 22.4% in 2011 to 44.5% in 2019; timely trastuzumab initiation remained stable at 18.0% over the same period. No appreciable differences in timely testing or trastuzumab initiation by age, sex, race or payer category were noted. Patients with early-stage GEA who subsequently developed metastatic disease were less likely to undergo timely HER2 testing and trastuzumab initiation than those with metastatic disease at diagnosis (PR 0.69, 95% CI 0.64-0.75 for testing; PR 0.44, 95% CI 0.28-0.69 for therapy). Similar findings were seen for patients who did not receive surgery (PR 0.56, 95% CI 0.47-0.65 for testing; PR 0.57, 95% CI 0.22-1.46 for therapy). Patients who started chemotherapy before learning their HER2 status (PR 1.42, 95% CI 1.05-1.90) and those with concordant HER2 immunohistochemistry and FISH results (PR 1.76, 95% CI 0.99-3.13) were more likely to initiate timely trastuzumab. Conclusions: Among patients with advanced GEA, guideline-recommended HER2 testing and anti-HER2 therapy initiation remain underutilized. Misclassification due to missing testing or treatment performed outside the Flatiron Network is a study limitation. Uptake of precision oncology may improve with implementation of universal HER2 testing of GEA patients regardless of stage and reflex multidisciplinary review of discordant HER2 test results.

Biomarker testing patterns and use of targeted therapy in Medicare Fee-for-Service (FFS) beneficiaries newly diagnosed with metastatic non-small cell lung cancer (mNSCLC).

278 Background: The number of targeted therapies approved for treatment of mNSCLC has increased over the past 5 years. Strategies to identify eligible patients with actionable mutations for targeted therapy include simultaneous testing of ≥ 2 genes via next generation sequencing (NGS) or multiple simultaneous gene testing (MSGT) and sequential single gene testing (SSGT). Current clinical practice guidelines strongly recommend broad molecular profiling in all patients for the simultaneous assessment of multiple genes, including EGFR, ALK and ROS1, that may have potential roles in cancer development. Limited real-world (RW) evidence is available describing the uptake of these strategies and receipt of targeted therapy. Methods: Medicare beneficiaries age 65 years or older, newly diagnosed with mNSCLC and tested for mutations of interest in mNSCLC (ALK, EGFR, ROS1, BRAF, HER2, KRAS, MET, NTRK, RET) from July 2014 - June 2018 were identified using Medicare FFS claims (100% sample) linked to biomarker results in PROGNOS NSCLC Explorer. Patients were followed from date of first metastatic diagnosis and stratified by line of therapy, testing strategy, and year of mNSCLC diagnosis. Those testing positive for an actionable biomarker were identified and then segmented by timing of receipt of a subsequent targeted therapy. Results: 12,272 beneficiaries met inclusion criteria: median age: 75 years, 51% were female, 86% white. Among mNSCLC patients with at least one biomarker test result, EGFR and ALK mutation status were the most commonly tested and reported in 85% and 63% respectively. Overall, 1540 (12.5%) tested positive for EGFR, ALK or ROS1. The relative use of NGS or MSGT vs. SSGT for biomarker testing increased over time, from 63% in 2014 to 80% in 2018. During this period, 789 patients were identified as having at least one positive biomarker test result prior to initiating 1L therapy: 635 were identified via NGS or MSGT while 154 were identified via SSGT. Despite a positive test for mutations of interest, only 292 patients received a targeted drug at 1L. Conclusions: This RW study of mNSCLC patients demonstrates an increasing trend to test patients for multiple biomarkers at once via NGS or other MSGT methods. The number of patients receiving appropriate targeted therapies was low, suggesting the need to address the barriers to administration of guideline-recommended therapy.

Differences in biomarkers and molecular pathways according to age for patients with HFrEF.

Elderly patients with heart failure with reduced ejection fraction (HFrEF) have worse prognosis and less often receive guideline-recommended therapies. We aim to better understand the underlying pathophysiological processes associated with ageing in HFrEF potentially leading to targeted therapies in this vulnerable population. From a panel of 363 cardiovascular biomarkers available in 1611 patients with HFrEF in the BIOSTAT-CHF index cohort and cross-validated in 823 patients in the BIOSTAT-CHF validation cohort, we tested which biomarkers were dysregulated in patients aged >75 vs. <65 years. Second, pathway overrepresentation analyses were performed to identify biological pathways linked to higher plasma concentrations of biomarkers in elderly vs. younger patients. After adjustment, multiple test correction [false discovery rate (FDR) 1%], and cross-validation, 27/363 biomarkers were associated with older age, 22 positively and 5 negatively. The biomarkers that were positively associated with older age were associated with tumour cell regulation, extra-cellular matrix organization, and inflammatory processes, whereas biomarkers negatively associated with older age were associated with pathways that may point to cell proliferation and tumourigenesis. Among the 27 biomarkers, WFDC2 (WAP four-disulphide core domain protein 2)-that broadly functions as a protease inhibitor-was associated with older age and had the strongest association with all outcomes. No protein-by-sex interaction was observed. In elderly HFrEF patients, pathways associated with extra-cellular matrix organization, inflammatory processes, and tumour cell regulation were activated, while pathways associated with tumour proliferation functions were down-regulated. These findings may help in a better understanding of the ageing processes in HFrEF and identify potential therapeutic targets.

Reader response: The dimension of preventable stroke in a large representative patient cohort.

Boehme et al.1 examine the burden of untreated risk factors for stroke in 1,730 patients with ischemic stroke/TIA from the Poststroke Disease Management STROKE-CARD trial. They chose to focus on 8 risk factors amenable to drug therapy (hypertension, hypercholesterolemia, atrial fibrillation, previous atherosclerotic cardiovascular disease, diabetes mellitus, carotid stenosis, unrecognized TIA, and the presence of a mechanical heart valve) and 3 lifestyle risk behaviors (smoking, obesity, alcohol excess). An important omission from this list is the presence of chronic kidney disease (CKD). There is a strong association between CKD and stroke,2 which is under-recognized and only addressed in current guidelines in terms of its potential to limit or alter otherwise established treatments.3 There is therapeutic nihilism associated with CKD whereby they are less likely to receive important guideline-recommended therapies, particularly oral anti-coagulants.4 It would be interesting to know what the prevalence of CKD was in this patient cohort and whether its presence increased the likelihood of poor risk factor control. There is a need for dedicated stroke prevention trials in this group and for closer collaboration between neurologists and nephrologists to bridge this therapeutic gap.5

Treatment patterns, outcomes and clinical characteristics in advanced renal cell carcinoma: a real-world US study.

Aim: Assessing treatment patterns, outcomes and clinical characteristics in advanced renal cell carcinoma clinical practice. Materials & methods: A US cross-sectional physician survey conducted February-September 2019. Results: Surveyed physicians reported first-line treatment of 445 patients involving tyrosine kinase inhibitor monotherapy (51.0%), immuno-oncology (IO/IO combination) therapy (25.8%) or other regimens (23.1%). A total of60.9% had physician-assessed IMDC risk. Of these 61.9, 50.9 and 27.6% of patients with favorable, intermediate and poor risk, respectively, received tyrosine kinase inhibitor monotherapy. A total of16.7, 26.9 and 34.5% of patients with favorable, intermediate or poor risk received IO/IO combination therapy. Complete/partial responses (∼35% patients) remained comparable across first-line treatments. Conclusion: Guideline-recommended therapies are not widely prescribed. Many patients experienced poor clinical outcomes highlighting a need for more effective treatments.

Effect of Dapagliflozin on Outpatient Worsening of Patients With Heart Failure and Reduced Ejection Fraction: A Prespecified Analysis of DAPA-HF.

In the DAPA-HF trial (Dapagliflozin and Prevention of Adverse Outcomes in Heart Failure), dapagliflozin, added to guideline-recommended therapies, reduced the risk of mortality and heart failure (HF) hospitalization. We examined the frequency and significance of episodes of outpatient HF worsening, requiring the augmentation of oral therapy, and the effects of dapagliflozin on these additional events. Patients in New York Heart Association functional class II to IV, with a left ventricular ejection fraction ≤40% and elevation of NT-proBNP (N-terminal pro-B-type natriuretic peptide), were eligible. The primary outcome was the composite of an episode of worsening HF (HF hospitalization or an urgent HF visit requiring intravenous therapy) or cardiovascular death, whichever occurred first. An additional prespecified exploratory outcome was the primary outcome plus worsening HF symptoms/signs leading to the initiation of new, or the augmentation of existing, oral treatment. Overall, 36% more patients experienced the expanded, in comparison with the primary, composite outcome. In the placebo group, 684 of 2371 (28.8%) patients and, in the dapagliflozin group, 527 of 2373 (22.2%) participants experienced the expanded outcome (hazard ratio, 0.73 [95% CI, 0.65-0.82]; P<0.0001). Each component of the composite was reduced significantly by dapagliflozin. Over the median follow-up of 18.2 months, the number of patients needed to treat with dapagliflozin to prevent 1 experiencing an episode of fatal or nonfatal worsening was 16. Among the 4744 randomly assigned patients, the first episode of worsening was outpatient augmentation of treatment in 407 participants (8.6%), an urgent HF visit with intravenous therapy in 20 (0.4%), HF hospitalization in 489 (10.3%), and cardiovascular death in 295 (6.2%). The adjusted risk of death from any cause (in comparison with no event) after an outpatient worsening was hazard ratio, 2.67 (95% CI, 2.03-3.52); after an urgent HF visit, the adjusted risk of death was hazard ratio, 3.00 (95% CI, 1.39-6.48); and after a HF hospitalization, the adjusted risk of death was hazard ratio, 6.21 (95% CI, 5.07-7.62). In DAPA-HF, outpatient episodes of HF worsening were common, were of prognostic importance, and were reduced by dapagliflozin. Registration: URL: https://www.clinicaltrials.gov; Unique Identifier: NCT03036124.

Effects of luseogliflozin on arterial properties in patients with type 2 diabetes mellitus: The multicenter, exploratory LUSCAR study.

Sodium‐glucose cotransporter 2 (SGLT2) inhibitors reduce the occurrence of cardiovascular and renal complications in patients with type 2 diabetes mellitus (T2DM) and represent guideline‐recommended therapy in this indication. However, precise mechanisms underlying the beneficial cardiovascular effects of SGLT2 inhibitors are not fully understood. This study investigated the effects of the SGLT2 inhibitor, luseogliflozin, on arterial properties and home blood pressure (BP) in patients with T2DM. This multicenter, single‐arm study enrolled adults with T2DM, glycosylated hemoglobin (HbA1c) 6.5%‐8.9% in the previous 4 weeks, and an indication for new/additional antidiabetic therapy. Luseogliflozin 2.5 mg/d was given for 12 weeks. Primary outcome was change in cardio‐ankle vascular index (CAVI) from baseline to Week 4 and Week 12. Home and office BP, BP variability, and metabolic parameters were secondary endpoints. Forty‐seven patients (mean age 63.5 ± 10.7 years) treated with luseogliflozin were included in the full analysis set. CAVI did not change significantly from baseline (mean [95% confidence interval] 8.67 [8.37‐8.97]) to Week 12 (8.64 [8.38‐8.91]; P = .750), but there were significant reductions from baseline in morning home BP, HbA1c, body weight, body mass index, and serum uric acid levels during luseogliflozin therapy. The reduction in morning home systolic BP was ≥ 5 mm Hg and was independent of baseline BP and BP control status. In conclusion, there was no change in arterial stiffness (based on CAVI) during treatment with luseogliflozin, but changes in BP and metabolic parameters were consistent with the known beneficial effects of SGLT2 inhibitors in T2DM.

Evaluation of a pharmacist-led shared decision-making in atrial fibrillation and patients' satisfaction-a before and after pilot study.

Chronic complex diseases like atrial fibrillation have potential long-term economical and personal consequences. Shared decision-making principles may promote therapeutic compliance, satisfaction and outcomes. Pharmacists, as patient-advocates, play a key role in guiding them through complex clinical decisions about their chronic disease management and anticoagulation choices. To evaluate the impact of pharmacist-led shared decision making on patients' satisfaction and appropriateness of their anticoagulation therapy in newly diagnosed atrial fibrillation patients. A prospective 2-phase before and after single-centre study was conducted in an Australian hospital. Phase 1 provided usual care, and patients' satisfaction and appropriateness of their anticoagulation therapy were evaluated. Phase-2 assessed the impact on satisfaction and appropriateness of anticoagulant therapy following pharmacist-led interventions of shared decision making to promote patients' involvement. Patients with pharmacist-led shared decision making reported higher degree of appropriateness of anticoagulation therapy and satisfaction (36% vs 92%, P < 0.001; 25% vs 68, P < 0.001), respectively. Additionally, patients who had a pharmacist input during their hospital stay received guideline-recommended anticoagulant therapy and reported satisfaction with their management was also higher in stage 2 (21% vs 65%, p < 0.001). The study highlights pharmacist-led shared decision making in atrial fibrillation that contributes to patient satisfaction and appropriateness of therapy.

Optimal Medical Therapy Prescription in Patients with Acute Coronary Syndrome in the Netherlands: A Multicenter Pilot Registry.

BackgroundUnlike neighboring countries, the Netherlands does not have a national acute coronary syndrome (ACS) registry to evaluate quality of care.ObjectiveWe conducted a pilot registry in two hospitals to assess the prescription of guideline-recommended therapies in Dutch patients with ACS.MethodsWe included all consecutive patients with ST-elevation myocardial infarction (STEMI) and non-STEMI (NSTEMI) (n = 1309) admitted to two Dutch percutaneous coronary intervention centers between March 2015 and February 2016. We collected follow-up medication use and reasons for discontinuation at discharge and 1, 6, and 12 months post-discharge. We assessed the use of optimal medical therapy (OMT), defined as the combined prescription of aspirin, P2Y12 inhibitors, statins, β-blockers, and angiotensin-converting enzyme inhibitors or angiotensin-receptor blockers.ResultsOMT prescription was 43.2% at discharge, 60.1% at 1 month, and 28.7% at 12 months. At 1 month, OMT prescription was significantly lower in patients with NSTEMI (51.8 vs. 65.7% for STEMI; p < 0.001). OMT prescription was lower in women (6 months: 55.4 vs. 62.0%, p = 0.036) and in elderly patients.ConclusionIn this pilot study that aimed to extend a national Dutch ACS registry to patients with STEMI and NSTEMI, OMT prescription was comparable to that in other local registries, was lower in women and patients with NSTEMI, and decreased with increasing age.Electronic supplementary materialThe online version of this article (10.1007/s40256-020-00427-9) contains supplementary material, which is available to authorized users.

Global Quality Standard for Identification and Management of Severe Asthma

IntroductionSevere asthma is a debilitating, life-threatening disease associated with substantial global morbidity, mortality, and health care resource utilization. Patients may not receive guideline-directed medical care for severe asthma. Moreover, viable precision-based assessment tools and newer preventive therapies that can reduce the frequency of exacerbations and associated functional impact are underused. As a result, high rates of poorly controlled severe asthma persist, and patient health-related quality of life suffers.MethodsIn 2019, the Improve Access to Better Care Task Force of the PRECISION Steering Committee set out to develop a global template on quality standards for severe asthma care to support improved access to and delivery of quality care. This Quality Standard is grounded in the vast body of published evidence available for severe asthma care, published clinical guidelines (i.e., from the Global Initiative for Asthma in 2019 and the European Respiratory Society/American Thoracic Society in 2014), and the 2018 PRECISION-supported Charter to Improve Patient Care in Severe Asthma.ResultsThe Quality Standard developed emphasizes four key elements aimed at optimizing clinical care and outcomes in severe asthma: (1) organization of services, (2) timely identification and referral for suspected severe asthma, (3) specialized assessment and management of severe asthma to optimize outcomes, and (4) patient-centric care and shared decision-making that is reflective of the patient’s expectations, priorities, and values. Four key Quality Statements are provided, along with quality metrics and strategies for local adaptation to optimize implementation.ConclusionThis Global Quality Standard is intended to mobilize policymakers, health care providers, and patient advocacy groups to build consensus on the definition and expectations of quality care in severe asthma, to promote patient-centric care, to identify gaps in care and areas for improvement, and systematically implement improvement measures and outcomes and to reduce the burden of illness for patients with severe asthma.

Contribution of Penicillin Allergy Labels to Second-Line Broad-Spectrum Antibiotic Prescribing for Pediatric Respiratory Tract Infections

IntroductionAntibiotic allergies are overdiagnosed. This may lead to unnecessary use of second-line broader-spectrum agents in place of narrower-spectrum guideline-recommended first-line therapies especially for uncomplicated respiratory tract infections. The extent to which this occurs for children with respiratory tract infections is unknown.MethodsWe included outpatient encounters for patients < 18 years with acute respiratory tract infections (sinusitis, bronchitis, bronchiolitis, upper respiratory tract infection, pharyngitis, otitis media). Patients were classified as penicillin allergic based on the presence of an allergy label in the electronic medical record. First-line guideline-recommended antibiotics included penicillin, amoxicillin or amoxicillin-clavulanate; all others were considered second line. The percentage of patients treated with first-line versus second-line antibiotics was compared between those with and without penicillin allergy. Additionally, we calculated the contribution of penicillin allergy to overall use of second-line antibiotics.ResultsAmong 17,578 eligible encounters for respiratory tract infections, 1332 (8%) included patients with a penicillin allergy label. Overall, second-line antibiotics were prescribed in 15% of encounters. Second-line antibiotics were prescribed in 91% of encounters for penicillin-allergic patients, compared with 8% of encounters for non-allergic patients (P < 0.001). Patients with penicillin allergy labels accounted for 47% of all second-line antibiotic prescriptions.ConclusionIn a large population of pediatric outpatient encounters for acute respiratory tract infections, patients labeled with a penicillin allergy accounted for nearly half of second-line antibiotics, which are often broader spectrum. Efforts to de-label children with penicillin allergies have the potential to reduce broader-spectrum antibiotic use.

Effect of high-intensity statin preloading on TIMI flow in patients presenting with ST-elevation myocardial infarction undergoing primary percutaneous coronary intervention

BackgroundAcute ST-elevation myocardial infarction (STEMI) is a major cause of morbidity and mortality worldwide. Primary percutaneous coronary intervention (PCI) has improved the outcomes from STEMI and improved myocardial perfusion. However, there is still room for medical therapy to help perfuse the myocardium. The aim of this study was to assess the impact of high-intensity statins used prior to primary PCI in patients presenting with acute STEMI on myocardial perfusion. The study included 170 patients who presented with acute STEMI to Ain Shams University Hospitals and underwent primary percutaneous coronary intervention (PCI). They were divided into two groups where the first group received high-intensity statins (80 mg of atorvastatin or 20 mg of rosuvastatin) besides guideline-recommended therapy before primary PCI and the second group served as a control group and received guideline-recommended therapy, and high-intensity statins were given as usual after going back to the coronary care unit after primary PCI. Post-interventional thrombolysis in myocardial infarction (TIMI) flow grade and myocardial blush grade (MBG) were recorded, and ST-segment resolution was measured.ResultsThe LAD was the culprit vessel for the majority of patients in both groups. In the control group, there were 4 patients with TIMI I flow and MBG I, 13 with TIMI II flow and MBG II, and 68 with TIMI III flow and MBG III. Meanwhile, in the cases group, there was 1 patient with TIMI I flow and MBG I, 3 with TIMI II flow and MBG II, and 81 with TIMI III flow and MBG III. This difference was statistically significant with a P value of 0.010. There were 34 patients in the cases group who showed complete ST-segment resolution (40%) vs. 19 patients (22.4%) in the control group which was statistically significant with a P value of 0.013. In addition, ejection fraction had values of mean ± SD of 45.91 ± 5.49 in the cases group vs. 43.01 ± 8.80 in the control group which was statistically significant with a P value of 0.011.ConclusionHigh-intensity statin loading before primary PCI resulted in improved post-procedural TIMI flow, MBG, complete ST-segment resolution, and ejection fraction.

Novel therapies for advanced urologic cancers.

Systemic treatment of advanced urogenital malignancies has changed significantly in recent years and it will continue to change rapidly in upcoming years. It is the scope of this review article to providing the reader with the most recently approved treatment strategies to be used in daily routine for the individualized and most optimal treatment of our patients. Immunooncological therapy (IOT) has emerged as the treatment of choice in metastatic renal cell carcinoma and we describe the most relevant clinical trials and we will give some differential therapeutic recommendation who might be best treated with which combination therapy considering both oncological efficacy and treatment-related toxicity. New neoadjuvant treatment options for muscle-invasive bladder cancer are reported. With regard to metastatic prostate cancer, the landscape of medical therapy is continuously evolving and the new, and most relevant therapeutic strategies for metastatic hormone-naive and castration-resistant PCA are described. Last, but not least, we highlight latest developments in the management of advanced testis cancer. The novel treatment options reported in this article are ready for use in daily routine and already represent or will shortly represent new guideline-recommended therapies.

Effects of combined renin-angiotensin-aldosterone system inhibitor and beta-blocker treatment on outcomes in heart failure with reduced ejection fraction: insights from BIOSTAT-CHF and ASIAN-HF registries.

Angiotensin-converting enzyme inhibitors (ACEi)/angiotensin receptor blockers (ARB) and β-blockers are guideline-recommended first-line therapies in heart failure (HF) with reduced ejection fraction (HFrEF). Previous studies showed that individual drug classes were under-dosed in many parts of Europe and Asia. In this study, we investigated the association of combined up-titration of ACEi/ARBs and β-blockers with all-cause mortality and its combination with hospitalization for HF. A total of 6787 HFrEF patients (mean age 62.6 ± 13.2 years, 77.7% men, mean left ventricular ejection fraction 27.7 ± 7.2%) were enrolled in the prospective multinational European (BIOSTAT-CHF; n = 2100) and Asian (ASIAN-HF; n = 4687) studies. Outcomes were analysed according to achieved percentage of guideline-recommended target doses (GRTD) of combination ACEi/ARB and β-blocker therapy, adjusted for indication bias. Only 14% (n = 981) patients achieved ≥50% GRTD for both ACEi/ARB and β-blocker. The best outcomes were observed in patients who achieved 100% GRTD of both ACEi/ARB and β-blocker [hazard ratio (HR) 0.32, 95% confidence interval (CI) 0.26-0.39 vs. none]. Lower dose of combined therapy was associated with better outcomes than 100% GRTD of either monotherapy. Up-titrating β-blockers was associated with a consistent and greater reduction in hazards of all-cause mortality (HR for 100% GRTD: 0.40, 95% CI 0.25-0.63) than corresponding ACEi/ARB up-titration (HR 0.75, 95% CI 0.53-1.07). This study shows that best outcomes were observed in patients attaining GRTD for both ACEi/ARB and β-blockers, unfortunately this was rarely achieved. Achieving >50% GRTD of both drug classes was associated with better outcome than target dose of monotherapy. Up-titrating β-blockers to target dose was associated with greater mortality reduction than up-titrating ACEi/ARB.

Home monitoring with technology-supported management in chronic heart failure: a randomised trial

ObjectivesWe aimed to investigate whether digital home monitoring with centralised specialist support for remote management of heart failure (HF) is more effective in improving medical therapy and patients’ quality of...

Vascular Quality of Care Assessment: Clinicians' Adherence to Lipid-Lowering Therapy for Patients with Atherosclerotic Cardiovascular Disease

Lipid-lowering medication can considerably lessen the risk for cardiovascular events in patients with atherosclerotic cardiovascular disease (ASCVD). Despite well-publicized guidelines and the accessibility of effective therapies, many patients do not attain their lipid goals and remain at high cardiovascular risk. Guidelines recommend statins as first-line therapy to reduce cardiovascular morbidity and mortality in ASCVD. We aimed to analyze admission lipid levels in a broad contemporary population of patients with ASCVD attending a vascular clinic or admitted to an inpatient vascular unit. Patients with known ASCVD, current cholesterol levels, and lipid-lowering medications were documented and compared with published current Canadian Cardiovascular Society Guidelines recommendations for achieving <2.0mmol/L or >50% reduction in low-density lipoprotein cholesterol (LDL-C). Cholesterol levels (current and previous), demographic characteristics, cardiovascular risk factors, and medical therapy were assessed from available patient records. Two hundred eight adult patients were identified. The mean age of the patients was 72 (±10) years, and 76% were men. About half had peripheral arterial disease (n=118, 56.7%), one-third had coronary artery disease (n=78, 37.5%), and one-third had diabetes (n=76, 36.5%). Most were hypertensive (n=140, 67.3%) and half gave a history of dyslipidemia (n=103, 49.5%). Most patients (n=183, 88%) were taking a statin and the majority at a moderate-intensity dose (n=79, 43.2%) or high-intensity dose (n=101, 55.2%). However, 32.7% of patients (n=68) did not reach target of LDL-C level of <2.0mmol/L or had ≤50% reduction from the baseline level. Of the patients who did not reach goals, 7 (10.3%) did not fill their statin prescriptions in the last 3months. Only 26 patients (12.5%) were also on ezetimibe, a guideline-recommended second-line therapy if targets are not reached with maximally tolerated statin therapy. One patient, who was able to reach target LDL-C, was on evolocumab monotherapy, a PCSK9 inhibitor, a contemporary nonstatin therapy that could be considered in ASCVD in those not at LDL-C goal. Of the 16 patients who were not prescribed any lipid-lowering therapy and did not reach target, 8 (50%) did not have any identified or documented reasons. Of the remaining 8 patients, 7 (87.5%) reported intolerance or side effects to statins only, and could benefit from nonstatin LDL-lowering therapy. In this observational study, we established suboptimal adherence to guideline recommendations for statin therapy and hesitancy to use nonstatin LDL-lowering agents in high-risk patients with ASCVD. These treatment gaps have an enormous effect on achieving improved cardiovascular clinical outcomes and must be tackled.

Towards quadruple therapy for heart failure with reduced ejection fraction: DAPA-HF secondary analysis data

Patients with heart failure with reduced ejection fraction (HFrEF), despite optimal evidence-based treatment, have a high residual risk of adverse outcomes. The favorable results of studies on cardiovascular safety and the effectiveness of sodium-glucose cotransporter 2 (SGLT2) inhibitors in patients with type 2 diabetes (T2D), including outcomes associated with heart failure, were the reason for studying the effectiveness in patients with HFrEF regardless of the T2D status. For the first time in the DAPA-HF study, the SGLT2 inhibitor dapagliflozin in patients with HFrEF showed a positive effect on hard endpoints. Data of the secondary analysis confirmed the effectiveness of dapagliflozin regardless of the T2D status, therapy, age, and quality of life. The results of DAPA-HF have become a serious statement for changing the standards of the guideline-recommended therapy of HFrEF.

Treatment Patterns and Health Care Costs of Lupus Nephritis in a United States Payer Population.

ObjectiveTo describe the characteristics, treatment patterns, health care resource utilization (HCRU), and cost of care for members of a large United States (US) health insurance plan with lupus nephritis (LN).MethodsA retrospective observational study was conducted using a health insurance plan database to identify adult members with a diagnosis of LN. Medical and pharmacy claims were used to describe demographics, comorbidities, HCRU, and cost patterns over a 12-month follow-up period for each patient, between January 1, 2014, and December 31, 2016. All study variables were examined descriptively.ResultsA total of 1039 patients were available for analysis (median age, 47 years; 83% female). The median Charlson Comorbidity Index (CCI) was 3.3. Less than half (41%) of patients received immunosuppressive therapies commonly used to treat LN. Evidence indicated that 58% of the study population were prescribed corticosteroid therapy, in most cases (73%) for more than 60 days. Adverse events known to be associated with corticosteroid therapy were recorded in 58% of patients. Guideline-recommended preventive therapy with hydroxychloroquine was prescribed for 54% of members with LN. Nearly half (47%) of members with LN did not see a nephrologist and more than one-third (36%) did not see a rheumatologist over 1 year of follow-up. Rates of all-cause hospitalization and emergency department (ED) use were 25% and 35%, respectively. The mean all-cause per-member-per-month (PMPM) medical cost for the study population was $2801, with LN-specific costs accounting for $1147 PMPM.ConclusionPatients with LN who are insured through a large US health plan appeared to underutilize outpatient specialist services and guideline-recommended hydroxychloroquine therapy. Corticosteroid use and adverse events known to be associated with corticosteroids were common in this cohort.