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Agonistas do Receptor do Peptídeo 1 Semelhante ao Glucagon , Neoplasias da Glândula Tireoide , Humanos , Diabetes Mellitus Tipo 2/tratamento farmacológico , Agonistas do Receptor do Peptídeo 1 Semelhante ao Glucagon/efeitos adversos , Agonistas do Receptor do Peptídeo 1 Semelhante ao Glucagon/uso terapêutico , Hipoglicemiantes/efeitos adversos , Hipoglicemiantes/uso terapêutico , Metanálise como Assunto , Ensaios Clínicos Controlados Aleatórios como Assunto , Fatores de Risco , Neoplasias da Glândula Tireoide/induzido quimicamente , Neoplasias da Glândula Tireoide/epidemiologia , Revisões Sistemáticas como AssuntoRESUMO
Ischaemic cardiovascular diseases, including peripheral and coronary artery disease, myocardial infarction, and stroke, remain major comorbidities for individuals with type 2 diabetes (T2D) and obesity. During cardiometabolic chronic disease (CMCD), hyperglycaemia and excess adiposity elevate oxidative stress and promote endothelial damage, alongside an imbalance in circulating pro-vascular progenitor cells that mediate vascular repair. Individuals with CMCD demonstrate pro-vascular 'regenerative cell exhaustion' (RCE) characterized by excess pro-inflammatory granulocyte precursor mobilization into the circulation, monocyte polarization towards pro-inflammatory vs. anti-inflammatory phenotype, and decreased pro-vascular progenitor cell content, impairing the capacity for vessel repair. Remarkably, targeted treatment with the sodium-glucose cotransporter-2 inhibitor (SGLT2i) empagliflozin in subjects with T2D and coronary artery disease, and gastric bypass surgery in subjects with severe obesity, has been shown to partially reverse these RCE phenotypes. SGLT2is and glucagon-like peptide-1 receptor agonists (GLP-1RAs) have reshaped the management of individuals with T2D and comorbid obesity. In addition to glucose-lowering action, both drug classes have been shown to induce weight loss and reduce mortality and adverse cardiovascular outcomes in landmark clinical trials. Furthermore, both drug families also act to reduce systemic oxidative stress through altered activity of overlapping oxidase and antioxidant pathways, providing a putative mechanism to augment circulating pro-vascular progenitor cell content. As SGLT2i and GLP-1RA combination therapies are emerging as a novel therapeutic opportunity for individuals with poorly controlled hyperglycaemia, potential additive effects in the reduction of oxidative stress may also enhance vascular repair and further reduce the ischaemic cardiovascular comorbidities associated with T2D and obesity.
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Doenças Cardiovasculares , Doença da Artéria Coronariana , Diabetes Mellitus Tipo 2 , Hiperglicemia , Inibidores do Transportador 2 de Sódio-Glicose , Humanos , Diabetes Mellitus Tipo 2/diagnóstico , Diabetes Mellitus Tipo 2/tratamento farmacológico , Hipoglicemiantes/efeitos adversos , Inibidores do Transportador 2 de Sódio-Glicose/efeitos adversos , Doença da Artéria Coronariana/tratamento farmacológico , Receptor do Peptídeo Semelhante ao Glucagon 1/metabolismo , Doenças Cardiovasculares/tratamento farmacológico , Doenças Cardiovasculares/complicações , Obesidade/tratamento farmacológico , Obesidade/complicações , Hiperglicemia/complicações , Hiperglicemia/tratamento farmacológico , Glucose , RegeneraçãoRESUMO
Type 2 diabetes (T2D), obesity, and nonalcoholic fatty liver disease/nonalacoholic steatohepatitis (NAFLD/NASH) share mutual causalities. Medications that may offer clinical benefits to all three conditions are being developed. Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are approved for the management of T2D and obesity and there is great interest in evaluating higher doses of available GLP-1RAs and developing novel GLP-1RA-based co-agonists to provide greater reductions in glycated hemoglobin (HbA1c) and body weight as well as modifying NAFLD/NASH complications in clinically meaningful ways. High-dose GLP-1RAs and multi-hormonal strategies including GLP-1R agonism have either already been approved or are in development for managing T2D, obesity, or NASH. We provide a mechanistic outline with a detailed summary of the available clinical data and ongoing trials that are adjudicating the impact of high-dose GLP-1RAs, unimolecular, and multimolecular GLP-1R-based co-agonists in populations living with T2D, obesity, or NASH. The available trial findings are aligned with preclinical observations, showing clinical efficacy and safety thus providing optimism for the expansion of GLP-1R-based drug classes for managing the triad of T2D, obesity and NASH. Development, access, and wide-spread utilization of these new therapeutic approaches will offer important opportunities to markedly improve the collective global burden of T2D, obesity, and NASH.
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Diabetes Mellitus Tipo 2 , Hepatopatia Gordurosa não Alcoólica , Humanos , Diabetes Mellitus Tipo 2/tratamento farmacológico , Hepatopatia Gordurosa não Alcoólica/tratamento farmacológico , Hipoglicemiantes/farmacologia , Hipoglicemiantes/uso terapêutico , Agonistas do Receptor do Peptídeo 1 Semelhante ao Glucagon , Receptor do Peptídeo Semelhante ao Glucagon 1/agonistas , Obesidade/complicações , Obesidade/tratamento farmacológicoAssuntos
Diabetes Mellitus Tipo 2 , Polipeptídeo Inibidor Gástrico , Receptor do Peptídeo Semelhante ao Glucagon 2 , Humanos , Polipeptídeo Inibidor Gástrico/uso terapêutico , Frequência Cardíaca , Metanálise em Rede , Agonistas do Receptor do Peptídeo 1 Semelhante ao Glucagon , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/tratamento farmacológico , Receptor do Peptídeo Semelhante ao Glucagon 1 , Hipoglicemiantes/uso terapêuticoRESUMO
PURPOSE OF REVIEW: Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are approved for the management of type 2 diabetes (T2D) and obesity, and some are recommended for cardiorenal risk reduction in T2D. To enhance the benefits with GLP-RA mono-agonist therapy, GLP-1/glucose-dependent insulinotropic polypeptide (GIP) receptor co-agonists are in development to capitalize on the synergism of GLP-1 and GIP agonism. We review the mechanisms of action and clinical data for GLP-1/GIP receptor co-agonists in T2D and obesity and their potential role in cardiovascular protection. RECENT FINDINGS: Tirzepatide, a first-in-class unimolecular GLP-1/GIP receptor co-agonist, is approved for T2D and is awaiting approval for obesity management. Phase 3 trials in T2D cohorts revealed significant reductions in glycemia and body weight and superiority compared with GLP-1R mono-agonism with semaglutide. Tirzepatide has demonstrated significant body weight reductions in individuals with obesity but not diabetes. It enhances lipid metabolism, reduces blood pressure, and lowers liver fat content. Pooled phase 2/3 data showed cardiovascular safety in T2D while a post hoc analysis suggested tirzepatide slows the decline of kidney function in T2D. SUMMARY: GLP-1/GIP receptor co-agonists are a novel addition to the diabetes and obesity armamentarium. The cardiorenal-metabolic benefits position them as promising multiprong tools for metabolically complex individuals with chronic vascular complications.
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Diabetes Mellitus Tipo 2 , Receptores dos Hormônios Gastrointestinais , Humanos , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/metabolismo , Peptídeo 1 Semelhante ao Glucagon/metabolismo , Peptídeo 1 Semelhante ao Glucagon/farmacologia , Peptídeo 1 Semelhante ao Glucagon/uso terapêutico , Receptores dos Hormônios Gastrointestinais/agonistas , Receptores dos Hormônios Gastrointestinais/uso terapêutico , Obesidade/complicações , Obesidade/tratamento farmacológicoRESUMO
Insulin icodec is a once-weekly basal insulin analogue in late-phase clinical development. Similar efficacy and safety of icodec to once-daily basal insulin analogues have been reported in over 4,200 participants with type 2 diabetes from three phase II and five phase III trials. Indeed, glycated haemoglobin reduction was superior for icodec among insulin-naïve participants (ONWARDS 1, 3 and 5) and in those switching from a daily basal insulin in ONWARDS 2, with the latter trial demonstrating improved diabetes treatment satisfaction scores with insulin icodec versus insulin degludec.
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INTRODUCTION: Use of continuous glucose monitoring (CGM) in people with diabetes may provide a more complete picture of glycemic control than glycated hemoglobin (HbA1c) measurements, which do not capture day-to-day fluctuations in blood glucose levels. The randomized, crossover, phase IV SWITCH PRO study assessed time in range (TIR), derived from CGM, following treatment with insulin degludec or insulin glargine U100 in patients with type 2 diabetes at risk for hypoglycemia. This post hoc analysis evaluated the relationship between TIR and HbA1c, following treatment intensification during the SWITCH PRO study. METHODS: Correlation between absolute values for TIR (assessed over 2-week intervals) and HbA1c, at baseline and at the end of maintenance period 1 (M1; week 18) or maintenance period 2 (M2; week 36), were assessed by linear regression and using the Spearman correlation coefficient (rs). These methods were also used to assess correlation between change in TIR and change in HbA1c from baseline to the end of M1, both in the full cohort and in subgroups stratified by baseline median HbA1c (≥ 7.5% [≥ 58.5 mmol/mol] or < 7.5% [< 58.5 mmol/mol]). RESULTS: A total of 419 participants were included in the analysis. A moderate inverse linear correlation was observed between TIR and HbA1c at baseline (rs -0.54), becoming stronger following treatment intensification during maintenance periods M1 (weeks 17-18: rs -0.59) and M2 (weeks 35-36: rs -0.60). Changes in TIR and HbA1c from baseline to end of M1 were also linearly inversely correlated in the full cohort (rs -0.40) and the subgroup with baseline HbA1c ≥ 7.5% (rs -0.43). This was less apparent in the subgroup with baseline HbA1c < 7.5% (rs -0.17) (p-interaction = 0.07). CONCLUSION: Results from this post hoc analysis of data from SWITCH PRO, one of the first large interventional clinical studies to use TIR as the primary outcome, further support TIR as a valid clinical indicator of glycemic control. TRIAL REGISTRATION: ClinicalTrials.gov identifier, NCT03687827.
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Doenças Cardiovasculares , Sistema Cardiovascular , Diabetes Mellitus Tipo 2 , Doenças Retinianas , Doenças Cardiovasculares/complicações , Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/prevenção & controle , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/tratamento farmacológico , Receptor do Peptídeo Semelhante ao Glucagon 1/agonistas , Humanos , Hipoglicemiantes/efeitos adversosRESUMO
This guideline synthesizes clinical trial data supporting the role of glucagon-like peptide-1 receptor agonists and sodium-glucose co-transporter 2 inhibitors (SGLT2i) for treatment of heart failure (HF), chronic kidney disease, and for optimizing prevention of cardiorenal morbidity and mortality in patients with type 2 diabetes. It is on the basis of a companion systematic review and meta-analysis guided by a focused set of population, intervention, control, and outcomes (PICO) questions that address priority cardiorenal end points. The Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) system and a modified Delphi process were used. We encourage comprehensive assessment of cardiovascular (CV) patients with routine measurement of estimated glomerular filtration rate, urinary albumin-creatinine ratio, glycosylated hemoglobin (A1c), and documentation of left ventricular ejection fraction (LVEF) when evaluating symptoms of HF. For patients with HF, we recommend integration of SGLT2i with other guideline-directed pharmacotherapy for the reduction of hospitalization for HF when LVEF is > 40% and for the reduction of all-cause and CV mortality, hospitalization for HF, and renal protection when LVEF is ≤ 40%. In patients with albuminuric chronic kidney disease, we recommend integration of SGLT2i with other guideline-directed pharmacotherapy to reduce all-cause and CV mortality, nonfatal myocardial infarction, and hospitalization for HF. We provide recommendations and algorithms for the selection of glucagon-like peptide-1 receptor agonists and SGLT2i for patients with type 2 diabetes and either established atherosclerotic CV disease or risk factors for atherosclerotic CV disease to reduce all-cause and CV mortality, nonfatal stroke, and for the prevention of hospitalization for HF and decline in renal function. We offer practical advice for safe use of these diabetes-associated agents with profound cardiorenal benefits.
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Doenças Cardiovasculares , Diabetes Mellitus Tipo 2 , Insuficiência Cardíaca , Insuficiência Renal Crônica , Inibidores do Transportador 2 de Sódio-Glicose , Humanos , Canadá/epidemiologia , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/tratamento farmacológico , Receptor do Peptídeo Semelhante ao Glucagon 1/agonistas , Insuficiência Cardíaca/complicações , Hipoglicemiantes/uso terapêutico , Insuficiência Renal Crônica/complicações , Insuficiência Renal Crônica/tratamento farmacológico , Comportamento de Redução do Risco , Inibidores do Transportador 2 de Sódio-Glicose/farmacologia , Inibidores do Transportador 2 de Sódio-Glicose/uso terapêutico , Volume Sistólico , Função Ventricular Esquerda , Metanálise como Assunto , Revisões Sistemáticas como AssuntoRESUMO
People living with diabetes are at higher risk for stroke and have a poorer prognosis following a stroke event than those without diabetes. Data from cardiovascular outcome trials and meta-analyses indicate that GLP-1RAs (glucagon-like peptide 1 receptor agonists) reduce the risk of stroke in individuals with type 2 diabetes. Accordingly, many guidelines now recommend the addition of GLP-1RAs to ongoing antihyperglycemic regimens to lower the risk of stroke in type 2 diabetes. The current work summarizes evidence supporting the use of GLP-1RAs for stroke reduction in people with type 2 diabetes and offers 2 new resources for neurologists who are considering GLP-1RAs for their patients-a list of frequently asked questions with evidence-based answers on safely initiating and managing GLP-1RAs, and a practical decision-making algorithm to assist in using GLP-1RAs as part of a stroke reduction strategy.
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Diabetes Mellitus Tipo 2 , Acidente Vascular Cerebral , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/tratamento farmacológico , Peptídeo 1 Semelhante ao Glucagon , Receptor do Peptídeo Semelhante ao Glucagon 1/agonistas , Humanos , Neurologistas , Acidente Vascular Cerebral/tratamento farmacológicoAssuntos
Diabetes Mellitus Tipo 2 , Cetoacidose Diabética , Inibidores do Transportador 2 de Sódio-Glicose , Adulto , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/tratamento farmacológico , Cetoacidose Diabética/induzido quimicamente , Glucose , Humanos , Sódio , Inibidores do Transportador 2 de Sódio-Glicose/efeitos adversosRESUMO
Hemoadsorption with CytoSorb has been used as an adjunct in the treatment of severe coronavirus disease 2019 (COVID-19)-related respiratory failure. It remains unknown if CytoSorb hemoadsorption will alter sedative and analgesic dosing in critically ill patients on venovenous extracorporeal membrane oxygenation (VV-ECMO). We conducted a retrospective review of patients with severe COVID-19 requiring VV-ECMO for respiratory support. Patients who were enrolled in a clinical study of CytoSorb were compared with patients on VV-ECMO alone. Data were collected for the 72-hour CytoSorb therapy and an additional 72 hours post-CytoSorb, or a corresponding control time period. Sedative and analgesic doses were totaled for each day and converted to midazolam or fentanyl equivalents, respectively. The primary endpoint, change in sedative and analgesic requirements over time, were compared using a two-way mixed analysis of variance. Of the 30 patients cannulated for VV-ECMO for COVID-19, 4 were excluded, leaving 8 patients in the CytoSorb arm and 18 in the Control. There was no effect of CytoSorb therapy on midazolam equivalents over the 72-hour therapy (p = 0.71) or the 72 hours post-CytoSorb (p = 0.11). In contrast, there was a significant effect of CytoSorb therapy on fentanyl equivalents over the first 72 hours (p = 0.01), but this was not consistent over the 72-hours post-CytoSorb (p = 0.23). CytoSorb therapy led to significant increases in analgesic requirements without impacting sedative requirements. Further research is needed to define the relevance of CytoSorb hemoadsorption on critical care pharmacotherapy.
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COVID-19 , Oxigenação por Membrana Extracorpórea , Oxigenação por Membrana Extracorpórea/efeitos adversos , Humanos , Hipnóticos e Sedativos , Estudos Retrospectivos , SARS-CoV-2RESUMO
AIMS: To compare time in range (TIR) with use of insulin degludec U100 (degludec) versus insulin glargine U100 (glargine U100) in people with type 2 diabetes. MATERIALS AND METHODS: We conducted a randomized, crossover, multicentre trial comparing degludec and glargine U100 in basal insulin-treated adults with type 2 diabetes and ≥1 hypoglycaemia risk factor. There were two treatment periods, each with 16-week titration and 2-week maintenance phases (with evaluation of glucose using blinded professional continuous glucose monitoring). The once-weekly titration (target: 3.9-5.0 mmol/L) was based on pre-breakfast self-measured blood glucose. The primary endpoint was percentage of TIR (3.9â10.0 mmol/L). Secondary endpoints included overall and nocturnal percentage of time in tight glycaemic range (3.9-7.8 mmol/L), and mean glycated haemoglobin (HbA1c) and glucose levels. RESULTS: At baseline, participants (n = 498) had a mean (SD) age of 62.8 (9.8) years, a diabetes duration of 15.1 (7.7) years and an HbA1c level of 59.6 (11.0) mmol/mol (7.6 [1.0]%). Noninferiority and superiority were confirmed for degludec versus glargine U100 for the primary endpoint, with a mean TIR of 72.1% for degludec versus 70.7% for glargine U100 (estimated treatment difference [ETD] 1.43% [95% confidence interval (CI): 0.12, 2.74; P = 0.03] or 20.6 min/d). Overall time in tight glycaemic range favoured degludec versus glargine U100 (ETD 1.5% [95% CI: 0.15, 2.89] or 21.9 min/d). Degludec also reduced nocturnal time below range (TBR; <3.9 mmol/L) compared with glargine U100 (ETD -0.88% [95% CI: -1.34, -0.42] or 12.7 min/night; post hoc) and significantly fewer nocturnal hypoglycaemic episodes of <3.0 mmol/L were observed. CONCLUSIONS: Degludec, compared with glargine U100, provided more TIR and time in tight glycaemic range, and reduced nocturnal TBR in insulin-treated people with type 2 diabetes.
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Diabetes Mellitus Tipo 2 , Hipoglicemia , Adulto , Glicemia , Automonitorização da Glicemia , Estudos Cross-Over , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/epidemiologia , Hemoglobinas Glicadas/análise , Humanos , Hipoglicemia/induzido quimicamente , Hipoglicemia/epidemiologia , Hipoglicemiantes/efeitos adversos , Insulina Glargina/efeitos adversos , Insulina de Ação Prolongada , Pessoa de Meia-Idade , Fatores de RiscoRESUMO
PURPOSE OF REVIEW: Elevated levels of triglycerides, independent of low-density lipoprotein cholesterol (LDL-C) levels and statin therapy, are associated with heightened cardiovascular risk. RECENT FINDINGS: Mixed omega-3 fatty acid formulations, which contain varying amounts of docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA), lower triglycerides levels but trial results with omega-3 fatty acids combinations have generally been neutral for cardiovascular outcomes. In contrast, the REDUCE-IT trial with icosapent ethyl (IPE), a highly purified ethyl ester of EPA, demonstrated reduced cardiovascular risk in individuals with established atherosclerotic cardiovascular disease or diabetes with at least one additional risk factor, despite having relatively well controlled LDL-C levels but triglycerides at least 135âmg/dl while on statin therapy. IPE offers an important new avenue for cardiovascular risk management in statin-treated individuals with elevated triglycerides. SUMMARY: This review summarizes the results from outcome trials conducted with omega-3 fatty acids, differentiating between those with combinations of EPA/DHA and those with pure EPA, as well as imaging and preclinical data that help explain the different cardiovascular efficacy observed. A list of frequently asked questions with evidence-based responses is provided to assist our colleagues and their patients in the shared-decision process when considering if IPE is appropriate for cardiovascular risk reduction.
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Doenças Cardiovasculares , Ácido Eicosapentaenoico , Doenças Cardiovasculares/prevenção & controle , Ácido Eicosapentaenoico/análogos & derivados , Ácido Eicosapentaenoico/uso terapêutico , Fatores de Risco de Doenças Cardíacas , Humanos , Fatores de Risco , TriglicerídeosRESUMO
BACKGROUND: Coronavirus disease 2019 (COVID-19) remains a worldwide pandemic with a high mortality rate among patients requiring mechanical ventilation. The limited data that exist regarding the utility of extracorporeal membrane oxygenation (ECMO) in these critically ill patients show poor overall outcomes. This report describes our institutional practice regarding the application and management of ECMO support for patients with COVID-19 and reports promising early outcomes. METHODS: All critically ill patients with confirmed COVID-19 evaluated for ECMO support from March 10, 2020, to April 24, 2020, were retrospectively reviewed. Patients were evaluated for ECMO support based on a partial pressure of arterial oxygen/fraction of inspired oxygen ratio of less than 150 mm Hg or pH of less than 7.25 with a partial pressure of arterial carbon dioxide exceeding 60 mm Hg with no life-limiting comorbidities. Patients were cannulated at bedside and were managed with protective lung ventilation, early tracheostomy, bronchoscopies, and proning, as clinically indicated. RESULTS: Among 321 patients intubated for COVID-19, 77 patients (24%) were evaluated for ECMO support, and 27 patients (8.4%) were placed on ECMO. All patients were supported with venovenous ECMO. Current survival is 96.3%, with only 1 death to date in more than 350 days of total ECMO support. Thirteen patients (48.1%) remain on ECMO support, and 13 patients (48.1%) have been successfully decannulated. Seven patients (25.9%) have been discharged from the hospital. Six patients (22.2%) remain in the hospital, of which 4 are on room air. No health care workers who participated in ECMO cannulation developed symptoms of or tested positive for COVID-19. CONCLUSIONS: The early outcomes presented here suggest that the judicious use of ECMO support in severe COVID-19 may be clinically beneficial.
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COVID-19/terapia , Oxigenação por Membrana Extracorpórea , SARS-CoV-2 , Adulto , COVID-19/mortalidade , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos RetrospectivosRESUMO
Coronavirus disease 2019 (COVID-19) is associated with increased rates of deep vein thrombosis (DVT) and pulmonary embolism (PE). Pulmonary Embolism Response Teams (PERT) have previously been associated with improved outcomes. We aimed to investigate whether PERT utilization, recommendations, and outcomes for patients diagnosed with acute PE changed during the COVID-19 pandemic. This is a retrospective cohort study of all adult patients with acute PE who received care at an academic hospital system in New York City between March 1st and April 30th, 2020. These patients were compared against historic controls between March 1st and April 30th, 2019. PE severity, PERT utilization, initial management, PERT recommendations, and outcomes were compared. There were more cases of PE during the pandemic (82 vs. 59), but less PERT activations (26.8% vs. 64.4%, p < 0.001) despite similar markers of PE severity. PERT recommendations were similar before and during the pandemic; anticoagulation was most recommended (89.5% vs. 86.4%, p = 0.70). During the pandemic, those with PERT activations were more likely to be female (63.6% vs. 31.7%, p = 0.01), have a history of DVT/PE (22.7% vs. 1.7%, p = 0.01), and to be SARS-CoV-2 PCR negative (68.2% vs. 38.3% p = 0.02). PERT activation during the pandemic is associated with decreased length of stay (7.7 ± 7.7 vs. 13.2 ± 12.7 days, p = 0.02). PERT utilization decreased during the COVID-19 pandemic and its activation was associated with different biases. PERT recommendations and outcomes were similar before and during the pandemic, and led to decreased length of stay during the pandemic.
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Anticoagulantes/administração & dosagem , Tratamento Farmacológico da COVID-19 , COVID-19 , Hospitais Universitários , Pandemias , Embolia Pulmonar , SARS-CoV-2/metabolismo , Idoso , Idoso de 80 Anos ou mais , COVID-19/sangue , COVID-19/epidemiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Cidade de Nova Iorque/epidemiologia , Guias de Prática Clínica como Assunto , Embolia Pulmonar/sangue , Embolia Pulmonar/tratamento farmacológico , Embolia Pulmonar/epidemiologia , Estudos Retrospectivos , Índice de Gravidade de DoençaRESUMO
Glucagon-like peptide-1 receptor agonists and sodium-dependent glucose cotransporter-2 inhibitors have demonstrated clinically significant benefits on glycated hemoglobin, weight, blood pressure and cardiorenal outcomes. The emerging evidence from clinical trials and meta-analyses that assessed the combination of these 2 classes of drugs has been promising. An expert forum that included individuals with expertise in endocrine, cardiology and nephrology issues was held in May 2020 to review the literature on the metabolic and cardiorenal benefits of these 2 classes, independently and in combination, in adults with type 2 diabetes mellitus. Although hard outcome data are not available, the group concluded that the combination of glucagon-like peptide-1 receptor agonists with sodium-dependent glucose cotransporter-2 inhibitors is an emerging option for managing adults with type 2 diabetes as long as cost is not a barrier. Ongoing research may offer further insights on hard cardiorenal outcomes for this therapeutic combination as well as provide direction on the potential of this approach in obesity, nonalcoholic fatty liver disease, nonalcoholic steatohepatitis and populations without diabetes.
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Diabetes Mellitus Tipo 2/tratamento farmacológico , Receptor do Peptídeo Semelhante ao Glucagon 1/administração & dosagem , Inibidores do Transportador 2 de Sódio-Glicose/administração & dosagem , Pressão Sanguínea/efeitos dos fármacos , Pressão Sanguínea/fisiologia , Diabetes Mellitus Tipo 2/metabolismo , Diabetes Mellitus Tipo 2/fisiopatologia , Quimioterapia Combinada , Humanos , Rim/efeitos dos fármacos , Rim/fisiologia , Ensaios Clínicos Controlados Aleatórios como Assunto/métodosRESUMO
PURPOSE: The right ventricular outflow tract (RVOT) velocity time integral (VTI), an echocardiographic measure of stroke distance, correlates with cardiac index. We sought to determine the prognostic significance of low RVOT VTI on clinical outcomes among patients with acute pulmonary embolism (PE). MATERIALS AND METHODS: We conducted a retrospective review of echocardiograms on Pulmonary Embolism Response Team (PERT) activations at our institution. The main outcome was a composite of death, cardiac arrest, or hemodynamic deterioration. RESULTS: Of 188 patients, 30 met the combined outcome (16%) and had significantly lower RVOT VTI measurements (9.0 cm v 13.4 cm, p < 0.0001). The AUC for RVOT VTI at a cutoff of 10 cm was 0.78 (95% CI 0.67-0.90) with a sensitivity, specificity, negative predictive value, and positive predictive value of 0.72, 0.81, 0.94, and 0.42, respectively. Fifty-two patients of the cohort were classified as intermediate-high-risk PE and 21% of those met the combined outcome. RVOT VTI was lower among outcome positive patients (7.3 cm v 10.7 cm, p = 0.02). CONCLUSIONS: Low RVOT VTI is associated with poor clinical outcomes among patients with acute PE.