Guideline-recommended Therapy Research Articles

When to implant an ICD in patients with heart failure and reduced ejection fraction? Insights from the HF-OPT trial

Abstract Background In patients with de novo heart failure with reduced ejection fraction (HFrEF) improvement of left ventricular ejection fraction (LVEF) is expected to occur when started on guideline-recommended medical therapy (GRMT). However, the period of time, when LVEF improvement is completed, is unknown. Purpose Evaluation of improvement of LVEF >35% within the first year after de novo diagnosis of HFrEF with severely reduced LVEF <35%. Methods In the prospective HF-OPT-trial, patients with de novo HFrEF and LVEF ≤35% prescribed the wearable cardioverter defibrillator (WCD) were enrolled and followed up to one year. GRMT was initiated and uptitrated according current guidelines. LVEF improvement >35% under GRMT was echocardiographically assessed at day 0, day 90, day 180 and day 360. Results A total of 487 patients (59 years (IQR: 51-68), 27% women) were followed until day 180. Out of 487 patients 392 patients were followed additionally to day 360. Dosages of GRMT were significantly increased during follow-up (p<0.001) At 90 days, 46% (CI: 41%-50%) of the patients had LVEF improvement >35%. About half of those with persistently LVEF<35% at day 90 (46%, CI: 40%-52%) had LVEF improvement >35% by day 180, increasing the total rate of improvement >35% to 68% (CI: 63% - 72%). Until day 360 the rate of LVEF improvement >35% increased to 78%. Conclusions 78% of patients with de novo HFrEF showed improvement in LVEF >35% during the first year after diagnosis following GRMT. This finding impacts decision making for primary preventive ICD implantation.Development of LVEF.

Tibial Nerve Stimulation for Urge Urinary Incontinence and Overactive Bladder: Narrative Review of Randomized Controlled Trials and Applicability to Implantable Devices.

The tibial nerve is an established target for neuromodulation in the management of overactive bladder (OAB) and its associated symptoms, including urge urinary incontinence (UUI). Technologies are currently available to deliver tibial nerve stimulation (TNS) through percutaneous devices or through implantable devices. The benefits and safety of percutaneous TNS have led to it as a guideline-recommended therapy. However, patient compliance is limited by the burden of weekly office visits and the need for maintenance treatments. Further, insurance often only covers a limited number of lifetime visits for percutaneous TNS. These factors and others have led to the development, study, and utilization of implantable TNS devices. Implantable TNS devices deliver the same therapeutic mechanism of action for nerve stimulation with a permanent implanted device that provides at-home stimulation rather than in-office therapy delivery. Additionally, there is an added potential for dynamic and patient-centered stimulation. There is a large body of high-quality evidence published for TNS, including numerous randomized controlled trials published on percutaneous TNS which have consistently demonstrated superior efficacy to sham and similar efficacy to that of anticholinergic medications. Percutaneous TNS also performs better than conservative therapy including pelvic floor muscle training. The percutaneous and implantable approaches deliver nerve stimulation to the same target nerve, using the same mechanism of action. Therefore, data from randomized trials of percutaneous TNS are informative for implantable TNS devices. At the time of this article's publication, at least two implantable TNS devices have received marketing authorization from the Food and Drug Administration (FDA). The objective of this review is to discuss the mechanism of action for TNS and summarize the published literature from clinical trials of percutaneous TNS as a foundation of high-quality evidence for implantable devices targeting the tibial nerve.

Real-world outcomes in patients with chronic spontaneous urticaria receiving omalizumab: insights from a clinical practice survey

Objective: Chronic spontaneous urticaria (CSU) is a debilitating inflammatory skin condition, often impacting quality of life. International guidelines recommend omalizumab, an anti-immunoglobulin E antibody, for second-line treatment. Our objective was to understand patient characteristics associated with prescription of omalizumab, and assess real-world outcomes in patients with CSU treated with omalizumab. Methods: We analyzed data from the Adelphi Real World CSU Disease Specific Programme™, a cross-sectional survey with retrospective data collection (December 2020–October 2021) from physicians and patients with CSU in the United States. Results: Data from allergists (n = 45), dermatologists (n = 51), and primary care physicians (PCPs; n = 20) were included. At the time of data collection, one-third of patients were receiving omalizumab (n = 220) and 67% were eligible for but not receiving omalizumab (n = 455). Using logistic regression, the odds of receiving omalizumab were higher in patients whose entire bodies were affected by hives [OR = 2.551; 95% CI 1.502-4.333; p < 0.001] or with deteriorating/unstable prognoses at treatment initiation [OR = 2.219; 95% CI 1.031-4.777; p = 0.042], and lower in patients managed by PCPs [OR = 0.276; 95% CI 0.130-0.584; p < 0.001]. Estimates from an inverse probability weighted regression adjustment model indicated that patients receiving omalizumab had higher treatment satisfaction, improvements in itching, hives, angioedema, insomnia, and anxiety, and lower impact on work productivity, compared with patients not receiving omalizumab. Conclusion: Around two-thirds of patients with CSU considered eligible for omalizumab were not receiving the guideline-recommended therapy. Patients receiving omalizumab had better real-world outcomes compared with patients not receiving omalizumab. Ensuring patients receive the most appropriate treatment could benefit patients with CSU.

Patterns of Use of Endocrine and Hormonal Therapy in Patients with Gender Dysphoria [ID 2683388

INTRODUCTION: Gender dysphoria (GD) is the emotional distress experienced by transgender individuals. While hormonal and endocrine therapy has been shown to improve outcomes, there is a paucity of data assessing patterns of use. The objective of our study was to determine trends in use of therapy in patients with GD. METHODS: We utilized the MarketScan Research Databases to identify patients aged 18–64 years with GD from 2008 to 2021. Use of guideline-recommended hormonal therapy including testosterone for transgender males and estradiol, spironolactone, and GnRH agonists for transgender females was examined. Patients were included if they had at least one full year of continuous insurance and drug enrollment. The utilization rate of each agent for each given year and duration of the first hormonal treatment were examined. RESULTS: A total of 36,847 patients were identified. The cohort included 18,195 (49.4%) patients with self-reported gender as male, and 18,652 (50.6%) as female. Overall, 61.0% of the cohort used hormonal therapy including estradiol in 33.4%, spironolactone in 27.3%, testosterone in 25.7%, and GnRH agonists in 0.3%. Use of hormonal therapy increased in more recent years of the study. Overall, hormonal therapy was used in 55.9% of those aged 18–24 years, 64.3% of those 25–34 years, 66.8% of patients 35–44 years, 64.2% of those 45–54 years, and in 61.5% of patients aged 55–64 years. CONCLUSION: The use of endocrine and hormonal therapy among transgender individuals is substantial and has increased over the last decade.

Evaluating haemodynamic changes: vericiguat in patients with heart failure with reduced ejection fraction.

Vericiguat has been used to treat patients with heart failure with reduced ejection fraction (HFrEF) who demonstrated worsening heart failure despite treatment with other guideline-directed medical therapies. The haemodynamic effects of vericiguat remain unclear. This study enrolled 12 patients (median age, 63 [quartiles 53.5, 70] years; 16.7%(N=2) women) with symptomatic HFrEF (New York Heart Association functional class II-IV) who demonstrated worsening heart failure despite treatment with the four foundational guideline-recommended therapies between March and December 2022, with follow-ups completed in June 2023. A balloon-tipped pulmonary artery thermodilution catheter was placed in the right internal jugular vein to perform right heart catheterisation (RHC) on day 1. Haemodynamic data were acquired before and after vericiguat intake (2.5mg) on days 2 and 3. The data on days 2 and 3 were averaged. RHC was repeated on day 105 (37, 168). Oral intake of vericiguat 2.5mg decreased mean pulmonary artery pressure (19.3 [14.3, 26.8] mmHg) and pulmonary artery wedge pressure (PAWP) (11 [7.5, 15] mmHg) before the intake to mean pulmonary artery pressure (17.5 [12.5, 24] mmHg) and PAWP (9.3 [6.8, 14] mmHg) at 30min after (both P<0.05). Reduction in PAWP was also found from 14.5 [9.5, 19.5] mmHg on day 1 to 9.5 [6.5, 12.5] mmHg on day 105 (37, 168) (P<0.05), when vericiguat was titrated to 2.5mg 25% (N=3), 5mg 50% (N=6), and 10mg 25% (N=3). The consistent reduction in PAWP underscores the well-tolerated nature of vericiguat and its potential to enhance cardiac performance in patients with HFrEF.

The prevalence of cardiovascular diseases, chronic kidney disease, and obesity in patients with type 2 diabetes mellitus and the description of concurrent treatments: A two-center retrospective cross-sectional study in Saudi Arabia

BackgroundAtherosclerotic cardiovascular disease (ASCVD), heart failure (HF), chronic kidney disease (CKD), and obesity are associated with increased morbidity and mortality in patients with type 2 diabetes mellitus (T2DM). Nonetheless, their prevalence among patients with T2DM in Saudi Arabia (SA) remains unknown. As current guidelines recommend, these comorbidities require adding certain antidiabetic agents with cardiorenal benefits. However, the prescribers' adherence to these recommendations remains unclear. MethodsA two-center retrospective cross-sectional study was conducted including adult patients (≥18 years) with T2DM admitted to hospital or seen at outpatient clinics between January and December 2020. Patients were classified into two groups based on the presence or absence of ASCVD. Patients with no prior ASCVD history were further classified based on the 10-year ASCVD risk estimation. Endpoints of interest included the prevalence of ASCVD, HF, CKD, and obesity in patients with T2DM. We also evaluated the characteristics of the utilized antidiabetic agents, statin, and aspirin therapies.. ResultsOf the 1,218 included patients with T2DM, the majority were female (57.0 %), and aged 45–64 years (53.0 %) with a mean age of 59.3 ± 13.1 years. Hypertension and dyslipidemia were the most prevalent comorbidities (67.7 % and 69.0 %, respectively). Among all patients, 18.6 % had an established ASCVD and the prevalence of HF, CKD, and obesity were 5.1 %, 8.7 %, and 58.3 %, respectively. The most common types of ASCVD witnessed were revascularization (42.3 %), myocardial infarction (36.6 %), and stroke (33.9 %); with an increased prevalence of ASCVD as the age increases (52.8 % at age ≥ 65 years). In the non‐ASCVD group, the 10-year ASCVD risk was intermediate or high in 62.7 % of these patients. The rates of utilization of guidelines-recommended therapies were 83.6 % for metformin, 9.4 % for GLP-1 RA, 10.8 % for SGLT2i, 35.2 % for aspirin alone or in combination with clopidogrel, and 79.7 % for statin therapy. ConclusionsASCVD, HF, CKD, and obesity are common complications in patients with T2DM in SA, with low overall utilization of the recommended guidelines-recommended medical therapies. Multimodal strategies should be utilized to assess T2DM and its complications, and to improve prescribers' adherence to guidelines-recommended therapies.

Real-world characteristics and use patterns of patients treated with vericiguat: A nationwide longitudinal cohort study in Germany.

Vericiguat reduced clinical endpoints in patients experiencing worsening heart failure in clinical trials, but its implementation outside trials is unclear. This retrospective analysis of longitudinally collected data was based on the IQVIA™ LRx database, which includes ~ 80% of the prescriptions of the 73 million people covered by the German statutory health insurance. Between September 2021 and December 2022, vericiguat was initiated in 2916 adult patients. Their mean age was 73 ± 13 years and 28% were women. While approximately 70% were uptitrated beyond 2.5 mg, only 36% reached 10 mg. Median time to up-titration from 2.5 mg to 5 mg was 17 (quartiles: 11-33) days, and from 2.5 to 10 mg 37 (25-64) days, respectively. In 87% of thepatients, adherence to vericiguat was high as indicated by a medication possession ratio of ≥ 80%, and 67% of thepatients persistently used vericiguat during the first year. Women and older patients reached the maximal dose of 10 mg vericiguat less often and received other substance classes of guideline-recommended therapy (GDMT) less frequently. The proportion of patients receiving four pillars of GDMT increased from 29% before vericiguat initiation to 44% afterwards. In a real-world setting, despite higher age than in clinical trials, adherence and persistence of vericiguat appeared satisfactory across age categories. Initiation of vericiguat was associated with intensification of concomitant GDMT. Nevertheless, barriers to vericiguat up-titration and implementation of other GDMT, applying in particular to women and elderly patients, need to be investigated further.

Physician characteristics associated with antiviral prescriptions for older adults with COVID-19 in Japan: an observational study

ObjectivesAlthough guidelines recommend antiviral therapy for outpatients with COVID-19 who are at high risk of progressing to severe conditions, such as older adults, many patients do not receive appropriate treatment....

Medium-intensity statin with ezetimibe versus high-intensity statin in acute ischemic cerebrovascular disease (MESIA): A randomized clinical trial

BackgroundHigh-risk stroke patients are recommended to receive high-intensity statin therapy to reduce the risk of stroke recurrence. However, doubling the dosage of statin drugs did not increase the achievement rate of LDL-C target or provide additional clinical benefits, but significantly increased the risk of adverse reactions. Statins and ezetimibe work through different mechanisms and the combined use of statins and ezetimibe significantly improves outcomes with comparable safety profiles. We tested the hypothesis that moderate-intensity statin with ezetimibe may offer advantages over the conventional high-intensity statin regimen in terms of efficacy and safety. MethodsWe conducted a randomized controlled trial. Eligible participants were aged 18 years or older with acute ischemic cerebrovascular disease. We randomly assigned (1:1) participants within the acute phase of ischemic stroke, i.e., within 1 week after the onset of mild ischemic stroke (NIHSS score ≤ 5), within 1 month for severe cases (NIHSS score ≥ 16), and within 2 weeks for the rest, as well as patients with TIA within 1 week of symptom onset, to receive either moderate-intensity statin with ezetimibe (either 10–20 mg atorvastatin calcium tablets plus a 10 mg ezetimibe tablet, or 5–10 mg rosuvastatin calcium tablets once per day plus a 10 mg ezetimibe tablet once per day) or high-intensity statin (40 mg atorvastatin calcium tablets or 20 mg rosuvastatin calcium tablets once per day) for 3 months. Randomization was performed using a random number table method. The primary efficacy outcome was the level and achievement rate of LDL-C after 3 months of treatment, specifically LDL-C ≤ 1.8 mmol/L or a reduction in LDL-C ≥ 50 %. The secondary outcome was the incidence of new stroke or transient ischemic attack (TIA) within 3 months. The safety outcome was liver and renal function tests, and the occurrence of statin-related muscle events within 3 months. FindingsThis trial took place between March 15, 2022, and March 7, 2023. Among 382 patients screened, 150 patients were randomly assigned to receive either medium-intensity statins with ezetimibe (n = 75) or high-intensity statins (n = 75). Median age was 60.0 years (IQR 52.75-70.25); 49 (36.6 %) were women and 85 (63.4 %) were men. The target achievement of LDL-C at 3 months occurred in 62 (89.86 %) of 69 patients in the medium-intensity statin with ezetimibe group and 46 (70.77 %) of 65 patients in the high-intensity statin group (P=0.005, OR=0.273, 95 % CI: 0.106, 0.705). The reduction magnitude of LDL-C in moderate-intensity statin with ezetimibe group was significantly higher (-56.540 % vs -47.995 %, P=0.001). Moderate-intensity statin with ezetimibe group showing a trend of a greater reduction in LDL-C absolute value than high-intensity statin group but without statistical significance (-1.77±0.90 vs -1.50±0.89, P=0.077). New AIS or TIA within 3 months, liver and renal function tests, and the occurrence of statin-related muscle events within 3 months were also statistically insignificant. Multivariate logistic regression analysis showed that both gender and lipid-lowering regimen as independent risk factors influencing the rate of LDL-C achievement in individuals diagnosed with acute ischemic cerebrovascular disease, but only lipid-lowering regimen had predictive value. InterpretationCompared to guideline-recommended high-intensity statin therapy, moderate-intensity statin with ezetimibe further improved the achievement rate of LDL-C in patients with acute ischemic cerebrovascular disease, with a higher reduction magnitude in LDL-C. In terms of safety, there was no significant difference between the two regimens, suggesting that moderate-intensity statin with ezetimibe can also be considered as an initial treatment option for patients with acute ischemic cerebrovascular disease.

High-volume facilities are significantly more likely to use guideline-adherent systemic immunotherapy for metastatic Merkel cell carcinoma: implications for cancer care regionalization.

Merkel cell carcinoma (MCC) is a neuroendocrine skin cancer with a high rate of mortality. While still relatively rare, the incidence of MCC has been rapidly rising in the US and around the world. Since 2017, two immunotherapeutic drugs, avelumab and pembrolizumab, have been FDA-approved for the treatment of metastatic MCC and have revolutionized outcomes for MCC. However, real-world outcomes can differ from clinical trial data, and the adoption of novel therapeutics can be gradual. We aimed to characterize the treatment practices and outcomes of patients with metastatic MCC across the US. A retrospective cohort study of adult cases of MCC in the National Cancer Database diagnosed from 2004 to 2019 was performed. Multivariable logistic regressions to determine the association of a variety of patient, tumor, and system factors with likelihood of receipt of systemic therapies were performed. Univariate Kaplan-Meier and multivariable Cox survival regressions were performed. We identified 1017 cases of metastatic MCC. From 2017 to 2019, 54.2% of patients received immunotherapy. This increased from 45.1% in 2017 to 63.0% in 2019. High-volume centers were significantly more likely to use immunotherapy (odds ratio 3.235, p = 0.002). On univariate analysis, patients receiving systemic immunotherapy had significantly improved overall survival (p < 0.001). One-, 3-, and 5-year survival was 47.2% (standard error [SE] 1.8%), 21.8% (SE 1.5%), and 16.5% (SE 1.4%), respectively, for patients who did not receive immunotherapy versus 62.7% (SE 3.5%), 34.4% (SE 3.9%), and 23.6% (SE 4.4%), respectively, for those who did (Fig. 1). In our multivariable survival regression, receipt of immunotherapy was associated with an approximately 35% reduction in hazard of death (hazard ratio 0.665, p < 0.001; 95% CI 0.548-0.808). Our results demonstrate that the real-world survival advantage of immunotherapy for metastatic MCC is similar to clinical trial data. However, many patients with metastatic disease did not receive this guideline-recommended therapy in our most recent study year, and use of immunotherapy is higher at high-volume centers. This suggests that regionalization of care to high-volume centers or dissemination of their practices, may ultimately improve patient survival.

Optimizing Post-Acute Coronary Syndrome Dyslipidemia Management: Insights from the North American Acute Coronary Syndrome Reflective III

Introduction: Despite contemporary practice guidelines, a substantial number of post-acute coronary syndrome (ACS) patients fail to achieve guideline-recommended LDL-C thresholds. Our study aimed to investigate this guideline recommendations-to-practice care gap. Specifically, we aimed to identify opportunities where additional lipid-lowering therapies are indicated and explore reasons for the non-prescription of guideline-recommended therapies. Methods: ACS patients with LDL-C ≥1.81 mmol/L (70 mg/dL) despite maximally tolerated statin ± ezetimibe therapy (including those intolerant of ≥2 statins) were enrolled 1–12 months post-event from 27 Canadian and US sites from September 2018 to October 2020 and followed up for three visits during the 12 months post-event. We determined the proportion of patients who did not achieve Canadian/US guideline-recommended LDL-C thresholds, the number of patients who would have been eligible for additional lipid-lowering therapies, and reasons behind lack of escalation in lipid-lowering therapies when indicated. Individual patient and aggregate practice feedback, including guideline-recommended intensification suggestions, were provided to each physician. Results: Of the 248 patients enrolled in the pilot study (median age 64 [57, 73] years, 31.5% female and STEMI 27.4%), 75.4% were on high-intensity statins on the first visit. A total of 18.5% of those who attended all 3 visits had an LDL-C measured only at the first visit which was above the threshold. After 1 year of follow-up, 51.9% of patients achieved LDL-C thresholds at either visit 2 or 3. In the context of feedback reminding physicians about guideline-directed LDL-C-modifying therapy in their individual participating patients, we observed an increase in the use of ezetimibe and PCSK9 inhibitor therapy at 3–12 months. This was associated with a significant lowering of the mean LDL-C (from 2.93 mmol/L [baseline] to 2.09 mmol/L [3–6 months] to 1.87 mmol/L [6–12 months]) and a significantly greater proportion of patients (from 0% [baseline] to 38.6% [3–6 months] to 53.4% [6–12 months]) achieving guideline-recommended LDL-C thresholds. The most prevalent reasons behind the non-intensification of LDL-C-lowering therapy with ezetimibe and/or PCSK9i were LDL-C levels being close to target, the pre-existing use of other lipid-lowering therapies, patient refusal, and cost. Conclusion: Although most patients post-ACS were on high-intensity statin therapy, almost 50% failed to achieve guideline-recommended LDL-C thresholds by 1-year follow-up. Furthermore, additional lipid-lowering therapies in this high-risk group were underprescribed, and this might be linked to several factors including potential gaps in physician knowledge, treatment inertia, patient refusal, and cost.

Pharmacist-led intervention for older people with atrial fibrillation in long-term care (PIVOTALL study): a randomised pilot and feasibility study

BackgroundOlder care home residents are a vulnerable group of people with atrial fibrillation (AF) at high risk of adverse health events. The Atrial Fibrillation Better Care (ABC: Avoid stroke; Better symptom management; Cardiovascular and other comorbidity management) pathway is the gold-standard approach toward integrated AF care, and pharmacists are a potential resource with regards to its’ implementation. The aim of this study was to determine the feasibility of pharmacist-led medicines optimisation in care home residents, based on the ABC pathway compared to usual care.MethodsIndividually randomised, prospective pilot and feasibility study of older (aged ≥ 65 years) care home residents with AF (ISRCTN14747952); residents randomised to ABC pathway optimised care versus usual care. The primary outcome was a description of study feasibility (resident and care home recruitment and retention). Secondary outcomes included the number and type of pharmacist medication recommendations and general practitioner (GP) implementation.ResultsTwenty-one residents were recruited and 11 (mean age [standard deviation] 85.0 [6.5] years, 63.6% female) were randomised to receive pharmacist-led medicines optimisation. Only 3/11 residents were adherent to all three components of the ABC pathway. Adherence was higher to ‘A’ (9/11 residents) and ‘B’ (9/11 residents) components compared to ‘C’ (3/11 residents). Four ABC-specific medicines recommendations were made for three residents, and two were implemented by residents’ GPs. Overall ABC adherence rates did not change after pharmacist medication review, but adherence to ‘A’ increased (from 9/11 to 10/11 residents). Other ABC recommendations were inappropriate given residents’ co-morbidities and risk of medication-related adverse effects.ConclusionsThe ABC pathway as a framework was feasible to implement for pharmacist medication review, but most residents’ medications were already optimised. Low rates of adherence to guideline-recommended therapy were a result of active decisions not to treat after assessment of the net risk–benefit.

Strategies to reduce out-of-pocket medication costs for Canadians with peripheral arterial disease.

Given that peripheral arterial disease (PAD) disproportionately affects people of lower socioeconomic status, out-of-pocket expenses for preventive medications are a major barrier to their use. We carried out a cost comparison of drug therapies for PAD to identify prescribing strategies that minimize out-of-pocket expenses for these medications. Between March and June 2019, we contacted outpatient pharmacies in Hamilton, Ontario, Canada, to assess pricing of pharmacologic therapies at dosages included in the 2016 American College of Cardiology/American Heart Association guideline for management of lower extremity PAD. We also gathered pricing information for supplementary charges, including delivery, pill splitting and blister packaging. We calculated prescription prices with and without dispensing fees for 30-day brand-name and generic prescriptions, and 90-day generic prescriptions. Twenty-four pharmacies, including hospital-based, independent and chain, were included in our sample. In the most extreme scenario, total 90-day medication costs could differ by up to $1377.26. Costs were affected by choice of agent within a drug class, generic versus brand-name drug, quantity dispensed, dispensing fee and delivery cost, if any. By opting for prescriptions for 90 days or as long as possible, selecting the lowest-cost generic drugs available in each drug class, and identifying dispensing locations with lower fees, prescribers can minimize out-of-pocket patient medication expenses. This may help improve adherence to guideline-recommended therapies for the secondary prevention of vascular events in patients with PAD.

Pulmonary Hypertension: Intensification and Personalization of Combination Rx (PHoenix): A phase IV randomized trial for the evaluation of dose-response and clinical efficacy of riociguat and selexipag using implanted technologies.

Approved therapies for the treatment of patients with pulmonary arterial hypertension (PAH) mediate pulmonary vascular vasodilatation by targeting distinct biological pathways. International guidelines recommend that patients with an inadequate response to dual therapy with a phosphodiesterase type-5 inhibitor (PDE5i) and endothelin receptor antagonist (ERA), are recommended to either intensify oral therapy by adding a selective prostacyclin receptor (IP) agonist (selexipag), or switching from PDE5i to a soluble guanylate-cyclase stimulator (sGCS; riociguat). The clinical equipoise between these therapeutic choices provides the opportunity for evaluation of individualized therapeutic effects. Traditionally, invasive/hospital-based investigations are required to comprehensively assess disease severity and demonstrate treatment benefits. Regulatory-approved, minimally invasive monitors enable equivalent measurements to be obtained while patients are at home. In this 2 × 2 randomized crossover trial, patients with PAH established on guideline-recommended dual therapy and implanted with CardioMEMS™ (a wireless pulmonary artery sensor) and ConfirmRx™ (an insertable cardiac rhythm monitor), will receive ERA + sGCS, or PDEi + ERA + IP agonist. The study will evaluate clinical efficacy via established clinical investigations and remote monitoring technologies, with remote data relayed through regulatory-approved online clinical portals. The primary aim will be the change in right ventricular systolic volume measured by magnetic resonance imaging (MRI) from baseline to maximal tolerated dose with each therapy. Using data from MRI and other outcomes, including hemodynamics, physical activity, physiological measurements, quality of life, and side effect reporting, we will determine whether remote technology facilitates early evaluation of clinical efficacy, and investigate intra-patient efficacy of the two treatment approaches.

A population-based cohort defined risk of hyperkalemia after initiating SGLT-2 inhibitors, GLP1 receptor agonists or DPP-4 inhibitors to patients with chronic kidney disease and type 2 diabetes

Hyperkalemia is a common adverse event in patients with chronic kidney disease (CKD) and type 2 diabetes and limits the use of guideline-recommended therapies such as renin-angiotensin system inhibitors. Here, we evaluated the comparative effects of sodium-glucose cotransporter-2 inhibitors (SGLT-2i), glucagon-like peptide-1 receptor agonists (GLP-1RA) and dipeptidyl peptidase-4 inhibitors (DPP-4i) on the risk of hyperkalemia. We conducted a population-based active-comparator, new-user cohort study using claims data from Medicare and two large United States commercial insurance databases (April 2013-April 2022). People with CKD stages 3-4 and type 2 diabetes who newly initiated SGLT-2i vs. DPP-4i (141671 patients), GLP-1RA vs. DPP-4i (159545 patients) and SGLT-2i vs. GLP-1RA (93033 patients) were included. The primary outcome was hyperkalemia diagnosed in inpatient or outpatient settings. Secondary outcomes included hyperkalemia diagnosed in inpatient or emergency department setting, and serum potassium levels of 5.5 mmol/L or more. Pooled hazard ratios and rate differences were estimated after propensity score matching to adjust for over 140 potential confounders. Initiation of SGLT-2i was associated with a lower risk of hyperkalemia compared with DPP-4i (hazard ratio 0.74; 95% confidence interval 0.68-0.80) and contrasted to GLP-1RA (0.92; 0.86-0.99). Compared with DPP-4i, GLP-1RA were also associated with a lower risk of hyperkalemia (0.80; 0.75-0.86). Corresponding absolute rate differences/1000 person-years were -24.8 (95% confidence interval -31.8 to -17.7), -5.0 (-10.9 to 0.8), and -17.7 (-23.4 to -12.1), respectively. Similar findings were observed for the secondary outcomes, among subgroups, and across single agents within the SGLT-2i and GLP-1RA classes. Thus, SGLT-2i and GLP-1RA are associated with a lower risk of hyperkalemia than DPP-4i in patients with CKD and type 2 diabetes, further supporting the use of these drugs in this population.

Prescription patterns of antidiabetic and cardiovascular preventive medications in community-dwelling older adults with type 2 diabetes mellitus: a cross-sectional study.

To describe trends in antidiabetics drug prescription patterns in community-dwelling older adults with type 2 diabetes mellitus (T2DM) and to evaluate the use of cardiovascular preventive medications among those diagnosed with atherosclerotic cardiovascular disease (ASCVD). This cross-sectional, face-to-face interview study that comprised community-dwelling older adults (≥ 65 years) diagnosed with T2DM. The study questionnaire included the patients' demographics, clinical data, and current medication use. Patients with established ASCVD were further classified into low (i.e., not receiving evidence-based therapy or only one) and high (i.e., receiving at least two evidence-based therapies) composite score groups. Bivariate analysis followed by multivariable logistic regression analysis were performed to evaluate the demographic/clinical characteristics associated with the use of antidiabetic monotherapy/polytherapy and evidence-based pharmacotherapy. A total of 500 older adults were enrolled. The mean age of included participants was 73 ± 7 years, 310 participants (62%) were males, and 385 participants (77.0%) had established ASCVD. Antidiabetic monotherapy was reported in 251 participants (50.2%), with metformin followed by sulfonylureas being the most commonly prescribed drugs as monotherapy. The results of the multivariable analysis showed that age [odds ratio (OR) = 0.89, 95% CI: 0.85-0.94, P < 0.001], obesity (OR = 4.18, 95% CI: 1.63-10.36, P = 0.003), hypertension (OR = 4.2, 95% CI: 1.22-7.66, P = 0.04), and dyslipidemia (OR = 4.1, 95% CI: 1.28-8.30, P = 0.01), were significantly associated with the prescription of cardiovascular preventive medications. Only one in twenty-one participant with T2DM and ASCVD collectively received three guideline-recommended therapies, indicating a deficiency of utilization of cardiovascular preventive drugs.

Medication use of Canadians with chronic obstructive pulmonary disease: a cohort study

ObjectivesThe objectives of this study were to describe medication use, treatment patterns and adherence, as well as acute exacerbations of chronic obstructive pulmonary disease (AECOPD) among adults living with COPD.MethodsA...

Complementary role of governments, non-governmental organizations, industry, and medical societies in expanding bradycardia therapy access.

As the aging population continues to grow, so has the incidence of cardiovascular diseases, including bradycardia, with much of the burden falling on low- and middle-income countries (LMICs). Pacemaker therapy remains the only guideline-recommended therapy for symptomatic bradycardia, but due to the cost and expertise required for pacemaker implants, patients in LMICs have less access to pacemaker therapies. However, with the concerted effort of organizations (governments, non-governmental organizations, industry, and medical societies) strides can continue to be made in improving access to care. Governments play a role in extending health coverage to its citizens and improving their physical and digital healthcare infrastructure. Non-governmental organizations promote access and awareness through charity and advocacy programs. Industries can continue innovating technology that is both affordable and accessible. Medical societies provide guidelines for treatment and necessary educational and networking opportunities for physicians who serve in LMICs. All of these organizations have individual responsibilities and goals in expanding access to bradycardia therapy, which can be more easily realized by their continued collaboration.

National Trends in Racial and Ethnic Disparities in Use of Recommended Therapies in Adults with Atherosclerotic Cardiovascular Disease, 1999-2020

Despite efforts to improve the quality of care for patients with atherosclerotic cardiovascular disease (ASCVD), it is unclear whether the US has made progress in reducing racial and ethnic differences in utilization of guideline-recommended therapies for secondary prevention. To evaluate 21-year trends in racial and ethnic differences in utilization of guideline-recommended pharmacological medications and lifestyle modifications among US adults with ASCVD. This cross-sectional study includes data from the National Health and Nutrition Examination Survey between 1999 and 2020. Eligible participants were adults aged 18 years or older with a history of ASCVD. Data were analyzed between March 2022 and May 2023. Self-reported race and ethnicity. Rates and racial and ethnic differences in the use of guideline-recommended pharmacological medications and lifestyle modifications. The study included 5218 adults with a history of ASCVD (mean [SD] age, 65.5 [13.2] years, 2148 women [weighted average, 44.2%]), among whom 1170 (11.6%) were Black, 930 (7.7%) were Hispanic or Latino, and 3118 (80.7%) were White in the weighted sample. Between 1999 and 2020, there was a significant increase in total cholesterol control and statin use in all racial and ethnic subgroups, and in angiotensin-converting enzyme inhibitor (ACEI) and angiotensin receptor blocker (ARB) utilization in non-Hispanic White individuals and Hispanic and Latino individuals (Hispanic and Latino individuals: 17.12 percentage points; 95% CI, 0.37-37.88 percentage points; P = .046; non-Hispanic White individuals: 12.14 percentage points; 95% CI, 6.08-18.20 percentage points; P < .001), as well as smoking cessation within the Hispanic and Latino population (-27.13 percentage points; 95% CI, -43.14 to -11.12 percentage points; P = .002). During the same period, the difference in smoking cessation between Hispanic and Latino individuals and White individuals was reduced (-24.85 percentage points; 95% CI, -38.19 to -11.51 percentage points; P < .001), but racial and ethnic differences for other metrics did not change significantly. Notably, substantial gaps persisted between current care and optimal care throughout the 2 decades of data analyzed. In the period of 2017 to 2020, optimal regimens were observed in 47.4% (95% CI, 39.3%-55.4%), 48.7% (95% CI, 36.7%-60.6%), and 53.0% (95% CI, 45.6%-60.4%) of Black, Hispanic and Latino, and White individuals, respectively. In this cross-sectional study of US adults with ASCVD, significant disparities persisted between current care and optimal care, surpassing any differences observed among demographic groups. These findings highlight the critical need for sustained efforts to bridge these gaps and achieve better outcomes for all patients, regardless of their racial and ethnic backgrounds.

Achieving optimal doses in treatment of heart failure with reduced ejection fraction at Gia Dinh People's Hospital

Heart failure (HF) with reduced ejection fraction (HFrEF) is a complex clinical syndrome associated with high mortality, long hospital length of stay, high readmission rates, reduced exercise tolerance, and decreased quality of life, as well as requiring significant resources to support treatment and care 1. Currently, it is reported that approximately 50% of all heart failure cases are HFrEF. However, due to recent advancements in cardiovascular diagnostic imaging, earlier, and possibly more precise, detection of HFrEF is greatly enabled. Not only does this seemingly increase the incidence rate of HfrEF in the general population, but it also gives treatment facilities an advantage in improving the prognosis and average life expectancy for these newly rising cases of HFrEF 2. According to heart failure treatment guidelines by Heart Associations around the world, an effective, interdisciplinary, and coordinated care system needs to be applied to all heart failure patients, including the reduced ejection fraction heart failure group, in order to achieve optimal guidelinesrecommended therapy, reduce mortality and readmission. In addition, each patient needs to be provided with a detailed treatment plan, which comprises treatment goals, effective management of comorbidities, follow-up time, diet, and physical activity 6. Therefore, the critical role of HF management programs in improving symptoms and quality of life in both inpatient and outpatient settings has been well recognized and paid continuous attention for the last two decades, with regular updates on team-based healthcare systems and home-based patient care 8,9,10. Recent updates in treatment guidelines have highlighted the role of the treating physician in customizing and adjusting the therapeutic drugs’ doses, to match those recommended as target or optimal, which must also be well-tolerated by the patients, with the aim of improving clinical outcomes 12. Therefore, it could be deduced that not only the sheer application of the four evidence-based foundational treatment but also dose adjustment over time of each one, should be collectively recognized as the basis of treating patients with HFrEF. The operation of a highlyspecialized unit, solely dedicated to the management of HF, known as ‘Heart Failure Unit’, has proven its effectiveness, by means of optimization of medical therapy, irrespective of baseline EF, but most notably reduced EF. Therefore, patients’ symptoms and readmission rate in facilities with “Heart Failure Unit” has witnessed a noticeable reduction. In today’s Vietnam, many tertiary medical facilities have implemented such centralized heart failure care models, and the Cardiology Department of Nhan dan Gia Dinh Hospital is definitely not an exception. The Heart Failure Unit in our department has been established and operating with a soulful dedication to providing HF patients with utmost comprehensive care and guideline-recommended therapy.