RESUMO
AIMS: This post hoc analysis investigated the effect of dulaglutide on cardiovascular disease (CVD) risk factors in subgroups of participants at increased CVD risk in the AWARD-11 study. METHODS: Participants who received once weekly dulaglutide 1.5, 3.0 or 4.5 mg for 52 weeks were categorized according to their baseline Framingham CVD risk category [low (N = 295), medium (N = 481) and high (N = 1054) risk], as well as their baseline CVD risk according to the REWIND study eligibility criteria (N = 953). Serum lipids and vital signs were assessed at baseline and at 52 weeks. Data were analysed as least squares mean percentage change from baseline for lipids and least squares mean change from baseline for vital signs. RESULTS: Demographic and baseline clinical characteristics were balanced across doses within the CVD risk groups. In the high Framingham CVD risk and REWIND-like groups, dulaglutide resulted in dose-related decreases in total cholesterol (≤6.0%), non-high-density lipoprotein cholesterol (≤8.8%), very-low-density lipoprotein cholesterol (≤19.4%) and triglycerides (≤21.5%), with little change in low-density lipoprotein cholesterol and high-density lipoprotein cholesterol. Systolic and diastolic blood pressure decreased up to 5.6 mmHg and 1.6 mmHg, respectively, and heart rate increased up to 2 beats/min. CONCLUSIONS: This post hoc analysis suggests the magnitude of the favourable effects of dulaglutide 3.0 mg and 4.5 mg on several cardiometabolic CVD risk factors was similar to, if not greater than, those of dulaglutide 1.5 mg among participants with type 2 diabetes and increased CVD risk. CLINICALTRIALS: gov Identifier: NCT03495102.
Assuntos
Doenças Cardiovasculares , Diabetes Mellitus Tipo 2 , Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/etiologia , Doenças Cardiovasculares/prevenção & controle , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/tratamento farmacológico , Peptídeos Semelhantes ao Glucagon/efeitos adversos , Peptídeos Semelhantes ao Glucagon/análogos & derivados , Humanos , Hipoglicemiantes/efeitos adversos , Fragmentos Fc das Imunoglobulinas/efeitos adversos , Lipídeos , Proteínas Recombinantes de Fusão/efeitos adversos , Fatores de RiscoRESUMO
The AWARD-11 trial demonstrated the safety and efficacy of dulaglutide 3.0 and 4.5 mg compared to dulaglutide 1.5 mg in patients with type 2 diabetes inadequately controlled with metformin. This post hoc analysis examined the change from baseline in glycated haemoglobin (HbA1c) and proportions of patients achieving HbA1c <7% at weeks 36 and 52 with dulaglutide 1.5 mg, 3.0 mg or 4.5 mg across clinically relevant baseline HbA1c subgroups (<8%; 8.0% to < 9.0%; 9.0% to < 10%; and ≥ 10%). Mean reductions in HbA1c were observed across all baseline HbA1c subgroups at 36 weeks (range of HbA1c change: 1.5 mg: -1.0% to -2.2%; 3.0 mg: -1.2% to -2.5%; and 4.5 mg: -1.2% to -3.2%). More patients randomized to 3.0 mg or 4.5 mg (vs. 1.5 mg) achieved HbA1c <7% at 36 weeks regardless of baseline HbA1c; the difference in proportions was greater at higher baseline HbA1c (P-interaction = 0.096). Similar patterns in glycaemic improvement and proportions achieving HbA1c <7% were observed at 52 weeks. Hypoglycaemia and gastrointestinal adverse events were similar among the HbA1c subgroups. Glycaemic control was improved with dulaglutide dose escalation from 1.5 mg to 3.0 mg or 4.5 mg across baseline HbA1c subgroups (<8%; 8.0% to < 9.0%; 9.0% to < 10%; and ≥ 10%).
Assuntos
Diabetes Mellitus Tipo 2 , Diabetes Mellitus Tipo 2/tratamento farmacológico , Peptídeos Semelhantes ao Glucagon/efeitos adversos , Peptídeos Semelhantes ao Glucagon/análogos & derivados , Hemoglobinas Glicadas/análise , Humanos , Hipoglicemiantes/efeitos adversos , Fragmentos Fc das Imunoglobulinas/efeitos adversos , Proteínas Recombinantes de Fusão , Resultado do TratamentoRESUMO
AIM: To evaluate the efficacy and safety of dulaglutide 3.0 and 4.5 mg versus 1.5 mg when used as an add-on to metformin in subgroups defined by age (<65 and ≥65 years). MATERIALS AND METHODS: Of 1842 patients included in this post hoc analysis, 438 were aged 65 years or older and 1404 were younger than 65 years. The intent-to-treat (ITT) population, while on treatment without rescue medication, was used for all efficacy analyses; the ITT population without rescue medication was used for hypoglycaemia analyses; all other safety analyses used the ITT population. RESULTS: Patients aged 65 years or older and those younger than 65 years had a mean age of 69.5 and 53.2 years, respectively. In each age subgroup, the reduction from baseline in HbA1c and body weight (BW), and the proportion of patients achieving a composite endpoint of HbA1c of less than 7% (<53 mmol/mol) with no weight gain and no documented symptomatic or severe hypoglycaemia, were larger for dulaglutide 3.0 and 4.5 mg compared with dulaglutide 1.5 mg, but the treatment-by-age interactions were not significant. The safety profile for the additional dulaglutide doses was consistent with that of dulaglutide 1.5 mg and was similar between the age subgroups. CONCLUSION: Dulaglutide doses of 3.0 or 4.5 mg provided clinically relevant, dose-related improvements in HbA1c and BW with no significant treatment-by-age interactions, and with a similar safety profile across age subgroups.
Assuntos
Diabetes Mellitus Tipo 2 , Hipoglicemiantes , Idoso , Diabetes Mellitus Tipo 2/tratamento farmacológico , Peptídeos Semelhantes ao Glucagon/efeitos adversos , Peptídeos Semelhantes ao Glucagon/análogos & derivados , Hemoglobinas Glicadas/análise , Humanos , Hipoglicemiantes/efeitos adversos , Fragmentos Fc das Imunoglobulinas/efeitos adversos , Pessoa de Meia-Idade , Proteínas Recombinantes de Fusão , Resultado do TratamentoRESUMO
AIM: To evaluate the impact of dulaglutide 3.0 and 4.5 mg versus 1.5 mg on body weight in patients with type 2 diabetes (T2D) based on exploratory analyses of the AWARD-11 trial. MATERIALS AND METHODS: Patients were randomized to once-weekly dulaglutide 1.5 (n = 612), 3.0 (n = 616) or 4.5 mg (n = 614) for 52 weeks. The primary objective was superiority of dulaglutide 3.0 and/or 4.5 mg over 1.5 mg in HbA1c reduction at 36 weeks. Secondary and exploratory assessments included weight reduction in the overall trial population and baseline body mass index (BMI) and HbA1c subgroups. RESULTS: At baseline, patients had a mean age of 57.1 years, HbA1c 8.6% (70 mmol/mol), weight 95.7 kg and BMI 34.2 kg/m2 . At 36 weeks, dulaglutide 3.0 and 4.5 mg were superior to 1.5 mg for weight change from baseline (1.5 mg, -3.1 kg; 3.0 mg, -4.0 kg [P = .001]; 4.5 mg, -4.7 kg [P < .001]). Higher dulaglutide doses were associated with numerically greater weight reduction compared with 1.5 mg in each baseline BMI and HbA1c subgroup. Absolute weight reduction increased with increasing BMI category, but percentage weight loss was similar between subgroups. Weight reductions with dulaglutide were greater in patients with lower versus higher baseline HbA1c. CONCLUSIONS: In patients with T2D, inadequately controlled by metformin, incremental weight loss was observed with dulaglutide 1.5, 3.0 and 4.5 mg doses regardless of baseline BMI or HbA1c. Although absolute weight loss was numerically greater in patients with higher baseline BMI, percentage of weight loss was similar between BMI subgroups.
Assuntos
Diabetes Mellitus Tipo 2 , Diabetes Mellitus Tipo 2/tratamento farmacológico , Peptídeos Semelhantes ao Glucagon/efeitos adversos , Peptídeos Semelhantes ao Glucagon/análogos & derivados , Hemoglobinas Glicadas/análise , Humanos , Hipoglicemiantes/efeitos adversos , Fragmentos Fc das Imunoglobulinas/efeitos adversos , Pessoa de Meia-Idade , Proteínas Recombinantes de FusãoRESUMO
OBJECTIVES: We sought to compare clinical outcomes after percutaneous coronary intervention (PCI) in patients on versus not on hemodialysis (HD) and examine whether high on-treatment platelet reactivity (HPR) further impacts outcomes among patients on HD. BACKGROUND: Both chronic kidney disease (CKD) and HPR are predictors of major adverse cardiac events (MACE) after PCI. METHODS: Two-year outcomes of patients from the prospective, multicenter ADAPT-DES study (N = 8,582) were analyzed according to HD status at enrollment. All patients underwent platelet function testing with the VerifyNow assay; HPR on clopidogrel was defined as P2Y12 reaction units (PRU) >208. RESULTS: Compared with non-HD patients, patients on HD (n = 85) had significantly higher baseline PRU (median 254 vs. 188, p = .001) and more frequently had HPR (61.7% vs. 42.5%, p < .001). HD was associated with increased 2-year rates of MACE (death, myocardial infarction (MI) or definite stent thrombosis (ST); 23.4% vs. 10.7%, p < .001). HD was also strongly associated with 2-year overall mortality, cardiac death, MI, target vessel revascularization, major bleeding, stroke and ST. Following adjustment for HPR and other covariates, HD was independently associated with overall mortality, MI, ST, and major bleeding at 2 years. The relationship between HD status and 2-year MACE was consistent in patients with and without HPR (Pinteraction = .78). CONCLUSIONS: Nearly two-thirds of patients on HD exhibited HPR on clopidogrel, and both HD and HPR were independently associated with 2-year adverse outcomes after DES implantation. However, the deleterious impact of HD on clinical outcomes was present in both patients with and without HPR.
Assuntos
Aspirina/uso terapêutico , Clopidogrel/uso terapêutico , Doença da Artéria Coronariana/terapia , Terapia Antiplaquetária Dupla , Intervenção Coronária Percutânea , Inibidores da Agregação Plaquetária/uso terapêutico , Diálise Renal , Insuficiência Renal Crônica/terapia , Idoso , Aspirina/efeitos adversos , Clopidogrel/efeitos adversos , Doença da Artéria Coronariana/diagnóstico por imagem , Doença da Artéria Coronariana/mortalidade , Trombose Coronária/mortalidade , Trombose Coronária/prevenção & controle , Stents Farmacológicos , Terapia Antiplaquetária Dupla/efeitos adversos , Terapia Antiplaquetária Dupla/mortalidade , Feminino , Alemanha , Humanos , Masculino , Pessoa de Meia-Idade , Intervenção Coronária Percutânea/efeitos adversos , Intervenção Coronária Percutânea/instrumentação , Intervenção Coronária Percutânea/mortalidade , Inibidores da Agregação Plaquetária/efeitos adversos , Testes de Função Plaquetária , Estudos Prospectivos , Sistema de Registros , Diálise Renal/efeitos adversos , Diálise Renal/mortalidade , Insuficiência Renal Crônica/diagnóstico , Insuficiência Renal Crônica/mortalidade , Medição de Risco , Fatores de Risco , Fatores de Tempo , Resultado do TratamentoRESUMO
The society for cardiovascular angiography and interventions (SCAI) think tank is a collaborative venture that brings together interventional cardiologists, administrative partners, and select members of the cardiovascular industry community for high-level field-wide discussions. The 2020 think tank was organized into four parallel sessions reflective of the field of interventional cardiology: (a) coronary intervention, (b) endovascular medicine, (c) structural heart disease, and (d) congenital heart disease (CHD). Each session was moderated by a senior content expert and co-moderated by a member of SCAI's emerging leader mentorship program. This document presents the proceedings to the wider cardiovascular community in order to enhance participation in this discussion, create additional dialogue from a broader base, and thereby aid SCAI and the industry community in developing specific action items to move these areas forward.
Assuntos
Cateterismo Cardíaco/tendências , Cardiologia/tendências , Angiografia Coronária/tendências , Cardiopatias/diagnóstico por imagem , Cardiopatias/terapia , Intervenção Coronária Percutânea/tendências , Difusão de Inovações , Cardiopatias/fisiopatologia , HumanosRESUMO
INTRODUCTION: In this study we characterized disease progression over 48 weeks among boys receiving deflazacort vs prednisone/prednisolone placebo arm treatment in two recent Duchenne muscular dystrophy (DMD) clinical trials. METHODS: Ambulatory boys with DMD receiving placebo in the phase 3 ataluren (N = 115) and tadalafil (N = 116) trials were included. The trials required at least 6 months of prior corticosteroid use and stable baseline dosing. Associations between corticosteroid use and 48-week changes in ambulatory function were estimated using mixed models. Adjusted differences between corticosteroid groups were pooled in a meta-analysis. RESULTS: In the meta-analysis, deflazacort-treated patients vs prednisone/prednisolone-treated patients experienced, on average, lower declines of 28.3 meters on 6-minute walk distance (95% confidence interval [CI], 5.7, 50.9; 2.9 seconds on rise from supine [95% CI, 0.9, 4.9 seconds]; 2.3 seconds on 4-stair climb [95% CI, 0.5, 4.1 seconds]; and 2.9 [95% CI, 0.1, 5.8] points on the North Star Ambulatory Assessment linearized score). DISCUSSION: Deflazacort-treated patients experienced significantly lower functional decline over 48 weeks.
Assuntos
Anti-Inflamatórios/uso terapêutico , Distrofia Muscular de Duchenne/tratamento farmacológico , Prednisona/uso terapêutico , Pregnenodionas/uso terapêutico , Criança , Progressão da Doença , Humanos , Masculino , Estudos Multicêntricos como Assunto , Prednisolona/uso terapêutico , Ensaios Clínicos Controlados Aleatórios como Assunto , Resultado do Tratamento , CaminhadaRESUMO
Research in northern latitudes confirms that climate teleconnections exert important influences on ungulate fitness, but studies from regions with milder climates are lacking. We explored the influence of the Pacific Decadal Oscillation (PDO), Northern Atlantic Oscillation (NAO), and El Niño-Southern Oscillation (ENSO) on male, 2.5-year-old white-tailed deer (Odocoileus virginianus) antler and body mass in Mississippi, USA, a region with mild winters and warm, humid summers. Explanatory variables were seasonal averages of each climate index extending back to 3 years prior to account for possible maternal and lag effects. Seasonal climate indices from the period of gestation and the first year of life were correlated with deer morphometrics. Reduced antler mass was largely correlated (R2 = 0.52) with PDO values indicating dry conditions during parturition and neonatal development and NAO values indicating warmer than normal winters during gestation and the first year of life. Body mass was less correlated (R2 = 0.16) to climate indices, responding negatively to warmer winter weather during the first winter of life. Climate may promote variable fitness among cohorts through long-term effects on male competition for dominance and breeding access. Because broad-scale climate indices simplify complex weather systems, they may benefit management at larger scales. Although this study compared climate with morphological variables, it is likely that demographic characteristics can likewise be modeled using climate indices. As climate change in this region is projected to include greater variability in summer precipitation, we may see concomitantly greater variability in fitness among cohorts of white-tailed deer.
Assuntos
Chifres de Veado , Cervos , Animais , Mudança Climática , El Niño Oscilação Sul , Masculino , Estações do Ano , Tempo (Meteorologia)RESUMO
BACKGROUND: Chronic total occlusion (CTO) percutaneous coronary intervention (PCI) typically requires a greater number of stents and longer stent length than non-CTO PCI, placing these patients at greater risk for adverse ischemic events. We sought to determine whether the association between high platelet reactivity (HPR) and the risk of ischemic events is stronger after CTO than non-CTO PCI. METHODS: Patients undergoing successful PCI in the multicenter ADAPT-DES study were stratified according to whether they underwent PCI of a CTO. HPR was defined as VerifyNow platelet reaction units >208. The study primary endpoint was the 2-year risk target vessel failure ([TVF] defined as cardiac death, myocardial infarction, or target lesion revascularization). RESULTS: CTO PCI was performed in 400 of 8448 patients. HPR was present in 34.5% of CTO PCI patients and 43.1% of non-CTO PCI patients (P = .0007). Patients undergoing CTO PCI with versus without HPR had significantly higher 2-year rates of TVF (15.0% versus 8.3%, P = .04) without significant differences in bleeding. HPR was an independent predictor of 2-year TVF (adjusted HR 1.16, 95% CI 1.02-1.34, P = .03) whereas CTO PCI was not (adjusted HR 0.89, 95% CI 0.65-1.22, P = .48). There was a significant interaction between CTO versus non-CTO PCI and PRU as a continuous variable for 2-year TVF (Pinteraction = 0.02). CONCLUSIONS: In ADAPT-DES, HPR was associated with an increased 2-year risk of TVF after PCI, an association that was at least as strong after CTO PCI compared with non-CTO PCI.
Assuntos
Plaquetas/fisiologia , Oclusão Coronária/sangue , Oclusão Coronária/cirurgia , Stents Farmacológicos/efeitos adversos , Isquemia Miocárdica/etiologia , Intervenção Coronária Percutânea/efeitos adversos , Idoso , Aspirina/uso terapêutico , Feminino , Fibrinolíticos/uso terapêutico , Humanos , Masculino , Pessoa de Meia-Idade , Inibidores da Agregação Plaquetária/uso terapêutico , Complicações Pós-Operatórias , Estudos Prospectivos , Desenho de PróteseRESUMO
AIMS: Dulaglutide, a once weekly GLP-1 receptor agonist, is approved at two doses (1.5 and 0.75 mg) for treatment of type 2 diabetes (T2D). Two higher doses of dulaglutide (3.0 and 4.5 mg) were evaluated for safety and efficacy to determine whether these doses warrant further study for improved control of glucose and body weight. MATERIALS AND METHODS: This 18-week, double-blind, phase 2 trial randomized 318 patients with T2D using ≥1500 mg metformin, to receive subcutaneous injection of placebo (n = 82), dulaglutide 1.5 mg (n = 81), dulaglutide 3.0 mg (n = 79) or dulaglutide 4.5 mg (n = 76). The primary objective was superiority of dulaglutide doses over placebo in reduction of HbA1c at 18 weeks. Secondary objectives included superiority of dulaglutide over placebo in change from baseline in body weight and fasting serum glucose (FSG) at 18 weeks. Investigational doses of dulaglutide were compared to the 1.5 mg dose as an exploratory objective. RESULTS: HbA1c reduction at 18 weeks was significantly greater with dulaglutide vs placebo (placebo, -0.44% ± 0.10% [-4.8 ± 1.1 mmol/mol]; dulaglutide 1.5 mg, -1.23% ± 0.10% [-13.5 ± 1.1 mmol/mol]; dulaglutide 3.0 mg, -1.31% ± 0.10% [-14.3 ± 1.1 mmol/mol]; dulaglutide 4.5 mg, -1.40% ± 0.10% [-15.3 ± 1.1 mmol/mol]; P < 0.001, each dose), as were changes in body weight (placebo, -1.6 ± 0.39 kg; dulaglutide 1.5 mg, -2.8 ± 0.39 kg; dulaglutide 3.0 mg, -3.9 ± 0.39 kg; dulaglutide 4.5 mg, -4.1 ± 0.41 kg; P < 0.001, each dose). All three dulaglutide doses significantly reduced FSG from baseline (1.5 mg, -36.2 ± 4.7 mg/dL [-2.0 ± 0.3 mmol/L]; 3.0 mg, -34.5 ± 4.5 mg/dL [-1.9 ± 0.3 mmol/L]; 4.5 mg, -38.0 ± 4.7 mg/dL [-2.1 ± 0.3 mmol/L]) vs placebo (-12.4 ± 4.5 mg/dL [-0.7 ± 0.3 mmol/L]) (P < 0.001, all). Safety profiles of the higher doses were consistent with the established safety profile for dulaglutide. Gastrointestinal events were mostly mild to moderate, and was dose-related for nausea. CONCLUSION: All three dulaglutide doses were superior to placebo in improving glycaemic control and reducing body weight in participants with T2D using metformin. The potential for doses of dulaglutide of 3.0 and 4.5 mg to provide additional glycaemic benefit and weight reduction with an acceptable safety profile, compared with the 1.5 mg dose, warrants further study in a phase 3 trial.
Assuntos
Diabetes Mellitus Tipo 2/tratamento farmacológico , Peptídeos Semelhantes ao Glucagon/análogos & derivados , Hipoglicemiantes/administração & dosagem , Fragmentos Fc das Imunoglobulinas/administração & dosagem , Metformina/administração & dosagem , Proteínas Recombinantes de Fusão/administração & dosagem , Adulto , Idoso , Glicemia/efeitos dos fármacos , Diabetes Mellitus Tipo 2/sangue , Método Duplo-Cego , Quimioterapia Combinada , Feminino , Peptídeos Semelhantes ao Glucagon/administração & dosagem , Hemoglobinas Glicadas/efeitos dos fármacos , Humanos , Masculino , Pessoa de Meia-Idade , Resultado do Tratamento , Redução de Peso/efeitos dos fármacosRESUMO
BACKGROUND: Whether high on-aspirin platelet reactivity (HAPR) confers an increased risk of adverse outcomes after percutaneous coronary intervention (PCI) remains unclear. We sought to examine the specific relationship between HAPR and clinical outcomes in ADAPT-DES. METHODS: A total of 8,526 "all-comer" patients in the ADAPT-DES registry who underwent placement of drug-eluting stents (DES) and were treated with aspirin and clopidogrel were assessed to measure platelet reactivity. HAPR was characterized as ≥550 aspirin reaction units and high on-clopidogrel platelet reactivity as >208 P2Y12 reaction units. Univariable and propensity-adjusted multivariable analyses were used to assess the relationship between HAPR and clinical outcomes. RESULTS: HAPR was present in 478 (5.6%) patients. Patients with HAPR were older and had more comorbid illnesses and more complex coronary anatomy. During 2-year follow-up, HAPR was not associated with increased rates of major adverse cardiac events (MACE), stent thrombosis, myocardial infarction, or all-cause mortality. In propensity-adjusted multivariable analyses, HAPR was not an independent predictor of MACE after successful PCI (multivariable adjusted hazard ratio: 1.04; 95% CI 0.64-1.69, P = .87). Nor was HAPR associated with reduced bleeding. Even among patients with concomitant high on-clopidogrel platelet reactivity, HAPR was not associated with worse ischemic outcomes (adjusted hazard ratio for 2-year MACE: 1.06; 95% CI 0.55-2.00, P = .87). CONCLUSIONS: HAPR was infrequently present in a large registry of patients undergoing PCI. There was no clear relationship between HAPR and 2-year clinical outcomes. Investigations of antiplatelet regimens without aspirin after DES implantation are ongoing and should inform future management of patients undergoing PCI.
Assuntos
Clopidogrel/administração & dosagem , Doença da Artéria Coronariana/cirurgia , Stents Farmacológicos , Intervenção Coronária Percutânea/métodos , Ativação Plaquetária/efeitos dos fármacos , Sistema de Registros , Idoso , Doença da Artéria Coronariana/tratamento farmacológico , Relação Dose-Resposta a Droga , Feminino , Seguimentos , Humanos , Injeções Intravenosas , Masculino , Pessoa de Meia-Idade , Inibidores da Agregação Plaquetária/administração & dosagem , Estudos Prospectivos , Fatores de Tempo , Resultado do TratamentoRESUMO
BACKGROUND: Prior small to modest-sized studies suggest a benefit of intravascular ultrasound (IVUS) guidance in noncomplex lesions. Whether IVUS guidance is associated with improved clinical outcomes after drug-eluting stent (DES) implantation in an unrestricted patient population is unknown. METHODS AND RESULTS: Assessment of Dual Antiplatelet Therapy With Drug-Eluting Stents (ADAPT-DES) was a prospective, multicenter, nonrandomized "all-comers" study of 8583 consecutive patients at 11 international centers designed to determine the frequency, timing, and correlates of stent thrombosis and adverse clinical events after DES. Propensity-adjusted multivariable analysis was performed to examine the relationship between IVUS guidance and 1-year outcomes. IVUS was utilized in 3349 patients (39%), and larger-diameter devices, longer stents, and/or higher inflation pressures were used in 74% of IVUS-guided cases. IVUS guidance compared with angiography guidance was associated with reduced 1-year rates of definite/probable stent thrombosis (0.6% [18 events] versus 1.0% [53 events]; adjusted hazard radio, 0.40; 95% confidence interval, 0.21-0.73; P=0.003), myocardial infarction (2.5% versus 3.7%; adjusted hazard radio, 0.66; 95% confidence interval, 0.49-0.88; P=0.004), and composite adjudicated major adverse cardiac events (ie, cardiac death, myocardial infarction, or stent thrombosis) (3.1% versus 4.7%; adjusted hazard radio, 0.70; 95% confidence interval, 0.55-0.88; P=0.002). The benefits of IVUS were especially evident in patients with acute coronary syndromes and complex lesions, although significant reductions in major adverse cardiac events were present in all patient subgroups those with including stable angina and single-vessel disease. CONCLUSIONS: In ADAPT-DES, the largest study of IVUS use to date, IVUS guidance was associated with a reduction in stent thrombosis, myocardial infarction, and major adverse cardiac events within 1 year after DES implantation. CLINICAL TRIAL REGISTRATION URL: http://www.clinicaltrials.gov. Unique identifier: NCT00638794.
Assuntos
Angiografia Coronária , Doença da Artéria Coronariana/terapia , Stents Farmacológicos , Intervenção Coronária Percutânea/métodos , Inibidores da Agregação Plaquetária/uso terapêutico , Ultrassonografia de Intervenção , Idoso , Doença da Artéria Coronariana/diagnóstico por imagem , Vasos Coronários/diagnóstico por imagem , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Infarto do Miocárdio/epidemiologia , Estudos Prospectivos , Fatores de Risco , Trombose/epidemiologia , Resultado do TratamentoRESUMO
BACKGROUND: The relation between platelet reactivity and stent thrombosis, major bleeding, and other adverse events after coronary artery implantation of drug-eluting stents has been incompletely characterised. We aimed to determine the relation between platelet reactivity during dual therapy with aspirin and clopidogrel and clinical outcomes after successful coronary drug-eluting stent implantation. METHODS: ADAPT-DES was a prospective, multicentre registry of patients successfully treated with one or more drug-eluting stents and given aspirin and clopidogrel at 10-15 US and European hospitals. We assessed platelet reactivity in those patients after successful percutaneous coronary intervention using VerifyNow point-of-care assays, and assigned different cutoffs to define high platelet reactivity. The primary endpoint was definite or probable stent thrombosis; other endpoints were all-cause mortality, myocardial infarction, and clinically relevant bleeding. We did a propensity-adjusted multivariable analysis to determine the relation between platelet reactivity and subsequent adverse events. This study is registered with ClinicalTrials.gov, number NCT00638794. FINDINGS: Between Jan 7, 2008, and Sept 16, 2010, 8665 patients were prospectively enrolled at 11 sites, of which 8583 were eligible. At 1-year follow-up, stent thrombosis had occurred in 70 (0·8%) patients, myocardial infarction in 269 (3·1%), clinically relevant bleeding in 531 (6·2%), and death in 161 (1·9%) patients. High platelet reactivity on clopidogrel was strongly related to stent thrombosis (adjusted HR 2·49 [95% CI 1·43-4·31], p=0·001) and myocardial infarction (adjusted HR 1·42 [1·09-1·86], p=0·01), was inversely related to bleeding (adjusted HR 0·73 [0·61-0·89], p=0·002), but was not related to mortality (adjusted HR 1·20 [0·85-1·70], p=0·30). High platelet reactivity on aspirin was not significantly associated with stent thrombosis (adjusted HR 1·46 [0·58-3·64], p=0·42), myocardial infarction, or death, but was inversely related to bleeding (adjusted HR 0·65 [0·43-0·99], p=0·04). INTERPRETATION: The findings from this study emphasise the counter-balancing effects of haemorrhagic and ischaemic complications after stent implantation, and suggest that safer drugs or tailored strategies for the use of more potent agents must be developed if the benefits of greater platelet inhibition in patients with cardiovascular disease are to be realised. FUNDING: Boston Scientific, Abbott Vascular, Medtronic, Cordis, Biosensors, The Medicines Company, Daiichi-Sankyo, Eli Lilly, Volcano, and Accumetrics.
Assuntos
Doença das Coronárias/cirurgia , Stents Farmacológicos , Intervenção Coronária Percutânea , Agregação Plaquetária/efeitos dos fármacos , Aspirina/uso terapêutico , Testes de Coagulação Sanguínea , Clopidogrel , Doença das Coronárias/tratamento farmacológico , Estenose Coronária/etiologia , Estenose Coronária/prevenção & controle , Stents Farmacológicos/efeitos adversos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Intervenção Coronária Percutânea/efeitos adversos , Intervenção Coronária Percutânea/métodos , Inibidores da Agregação Plaquetária/uso terapêutico , Sistemas Automatizados de Assistência Junto ao Leito , Estudos Prospectivos , Sistema de Registros , Fatores de Risco , Ticlopidina/análogos & derivados , Ticlopidina/uso terapêutico , Fatores de Tempo , Resultado do TratamentoAssuntos
Equipe de Assistência ao Paciente , Papel do Médico , Especialização , Cirurgiões , Substituição da Valva Aórtica Transcateter , Congressos como Assunto , Consenso , Humanos , Descrição de Cargo , Equipe de Assistência ao Paciente/normas , Especialização/normas , Cirurgiões/normas , Substituição da Valva Aórtica Transcateter/normasAssuntos
Cateterismo Cardíaco , Angiografia Coronária , Procedimentos Endovasculares , Cardiopatias Congênitas/terapia , Intervenção Coronária Percutânea , Doenças Vasculares Periféricas/terapia , Cateterismo Cardíaco/efeitos adversos , Cateterismo Cardíaco/instrumentação , Angiografia Coronária/efeitos adversos , Angiografia Coronária/instrumentação , Procedimentos Endovasculares/efeitos adversos , Procedimentos Endovasculares/instrumentação , Cardiopatias Congênitas/diagnóstico por imagem , Cardiopatias Congênitas/fisiopatologia , Humanos , Intervenção Coronária Percutânea/efeitos adversos , Intervenção Coronária Percutânea/instrumentação , Doenças Vasculares Periféricas/diagnóstico por imagem , Doenças Vasculares Periféricas/fisiopatologiaRESUMO
OBJECTIVE: To examine changes in glomerular hyperfiltration and other measures of kidney function in youth with type 2 diabetes treated with dulaglutide or placebo. RESEARCH DESIGN AND METHODS: Post hoc analysis was performed on kidney laboratory data from 154 youths (age 10-18 years) with type 2 diabetes enrolled in a completed placebo-controlled glycemic control trial of dulaglutide. RESULTS: Mean estimated glomerular filtration rate (eGFR) decreased from baseline to 26 weeks in participants treated with dulaglutide versus placebo (-5.8 vs. -0.1 mL/min/1.73 m2; P = 0.016). Decreases in eGFR were observed primarily in participants with baseline glomerular hyperfiltration. At 26 weeks, the prevalence of both glomerular hyperfiltration and proteinuria increased with placebo but decreased with dulaglutide (P = 0.014 and 0.004 vs. placebo, respectively). CONCLUSIONS: Dulaglutide was associated with attenuated glomerular hyperfiltration and proteinuria in youth with type 2 diabetes. The impact of these changes on the risk of diabetic kidney disease is unclear.
Assuntos
Albuminúria , Diabetes Mellitus Tipo 2 , Taxa de Filtração Glomerular , Peptídeos Semelhantes ao Glucagon , Fragmentos Fc das Imunoglobulinas , Proteinúria , Proteínas Recombinantes de Fusão , Humanos , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/fisiopatologia , Diabetes Mellitus Tipo 2/complicações , Adolescente , Criança , Proteinúria/fisiopatologia , Masculino , Feminino , Albuminúria/fisiopatologia , Proteínas Recombinantes de Fusão/uso terapêutico , Peptídeos Semelhantes ao Glucagon/análogos & derivados , Peptídeos Semelhantes ao Glucagon/uso terapêutico , Fragmentos Fc das Imunoglobulinas/uso terapêutico , Hipoglicemiantes/uso terapêutico , Nefropatias Diabéticas/fisiopatologia , Nefropatias Diabéticas/tratamento farmacológicoRESUMO
OBJECTIVE: To compare outcomes between US and non-US (OUS) sites in patients with non ST-elevation acute coronary syndromes (NSTEACS) and to evaluate potential reasons for differences in outcomes. BACKGROUND: There are little data comparing outcomes at US versus OUS sites in patients with NSTEACS managed with an invasive strategy. METHODS: The ACUITY trial randomized 13,819 patients with NSTEACS in 17 countries to an invasive approach with one of three strategies: (1) heparin plus glycoprotein platelet inhibitors (GPI), (2) bivalirudin plus GPI, or (3) bivalirudin alone. RESULTS: US patients were more often female, were younger, heavier, and had more diabetes, prior myocardial infarction (MI), and prior bypass surgery. US patients were less often treated with percutaneous coronary intervention but had more frequent drug-eluting stent use. US patients had lower mortality and higher MI rates at 30 days and 1 year and higher composite ischemic outcome at 30 days. After adjusting for differences in baseline variables, US patients had higher rates of MI and composite ischemic outcome at 30 days and higher rates of MI at 1 year {HR [95% confidence interval (CI)] = 1.36 [1.18-1.56], P < 0.0001} with no differences in mortality. There were no differences in treatment effects comparing bivalirudin with the other strategies between US and OUS sites. CONCLUSIONS: US versus OUS patients with NSTEACS had higher adjusted rates of MI and ischemia. The reasons for these differences are not clear but may be due to unmeasured confounders, different thresholds for event reporting, or valid differences in systems of care which may impact outcomes.
Assuntos
Síndrome Coronariana Aguda/terapia , Anticoagulantes/uso terapêutico , Ponte de Artéria Coronária , Disparidades em Assistência à Saúde , Intervenção Coronária Percutânea , Inibidores da Agregação Plaquetária/uso terapêutico , Síndrome Coronariana Aguda/complicações , Síndrome Coronariana Aguda/mortalidade , Idoso , Ponte de Artéria Coronária/efeitos adversos , Ponte de Artéria Coronária/mortalidade , Quimioterapia Combinada , Stents Farmacológicos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/etiologia , Intervenção Coronária Percutânea/efeitos adversos , Intervenção Coronária Percutânea/instrumentação , Intervenção Coronária Percutânea/mortalidade , Fatores de Risco , Fatores de Tempo , Resultado do Tratamento , Estados UnidosRESUMO
Twitter, which recently changed its name to "X," is a popular social media platform that is used widely across the world due to its easy accessibility through the internet. Due to more public familiarity, we referred to this social media platform as "Twitter (X)" in this article. Users can create posts, also called as "tweets" with a limitation of 280 characters and can add images, videos, and weblinks. While there are several social media platforms used by health care professionals, eg, Facebook, Instagram, Snapchat, TikTok, LinkedIn, and Periscope, Twitter (X) is an extremely popular platform among physicians, especially cardiologists. Due to its persistent growth and ever-expanding outreach, Twitter (X) is facilitating dissemination of scientific information including complex medical knowledge leading the way in collaborations, and in organizing and networking of various health care professionals, patients, and caregivers with shared medical interests. While there are several advantages of Twitter (X) as an important tool in our contemporary medical armamentarium, there are also some drawbacks. False information can be distributed effortlessly and can entrench unscientific beliefs as there is no peer-review process. Occasionally, discourteous discussions between health care professionals can be misinterpreted by users with limited medical knowledge. Other disadvantages include Health Insurance Portability and Accountability Act violations and hacking of accounts. Therefore, it is imperative for health care professionals interested to use this valuable tool to be familiar with and cautious about its potential risks and limitations.
RESUMO
Background Diabetes mellitus and high platelet reactivity (HPR) on clopidogrel are both associated with increased risk of ischemic events after percutaneous coronary intervention, but whether the HPR-associated risk of adverse ischemic events differs by diabetes mellitus status is unknown. Methods and Results ADAPT-DES (Assessment of Dual Antiplatelet Therapy With Drug-Eluting Stents) was a prospective, multicenter registry of patients treated with coronary drug-eluting stents. HPR was defined as P2Y12 reaction units >208 by the VerifyNow point-of-care assay. Cox multivariable analysis was used to assess whether HPR-associated risk of major adverse cardiac events (MACE; cardiac death, myocardial infarction, or stent thrombosis) varied for patients with insulin-treated diabetes mellitus (ITDM), non-ITDM, and no diabetes mellitus. Diabetes mellitus and HPR were included in an interaction analysis. Of 8582 patients enrolled, 2429 (28.3%) had diabetes mellitus, of whom 998 (41.1%) had ITDM. Mean P2Y12 reaction units were higher in patients with diabetes mellitus versus without diabetes mellitus, and HPR was more frequent in patients with diabetes mellitus. HPR was associated with consistently increased 2-year rates of MACE in patients with and without diabetes mellitus (Pinteraction=0.36). A significant interaction was present between HPR and non-insulin-treated diabetes mellitus versus ITDM for 2-year MACE (adjusted hazard ratio [HR] for non-ITDM, 2.28 [95% CI, 1.39-3.73] versus adjusted HR for ITDM, 1.02 [95% CI, 0.70-1.50]; Pinteraction=0.01). Conclusions HPR was more common in patients with diabetes mellitus and was associated with an increased risk of MACE in both patients with and without diabetes mellitus. In patients with diabetes mellitus, a more pronounced effect of HPR on MACE was present in lower-risk non-ITDM patients than in higher-risk patients with ITDM. Registration URL: https://clinicaltrials.gov/ct2/show/NCT00638794; Unique identifier: NCT00638794. ADAPT-DES (Assessment of Dual Antiplatelet Therapy With Drug-Eluting Stents).
Assuntos
Doença da Artéria Coronariana , Diabetes Mellitus , Intervenção Coronária Percutânea , Humanos , Inibidores da Agregação Plaquetária/efeitos adversos , Estudos Prospectivos , Fatores de Risco , Plaquetas , Clopidogrel/uso terapêutico , Clopidogrel/farmacologia , Isquemia/etiologia , Intervenção Coronária Percutânea/efeitos adversos , Resultado do Tratamento , Doença da Artéria Coronariana/complicações , Diabetes Mellitus/etiologiaRESUMO
The Generations trial, a multicenter, placebo-controlled, double-blind trial, compared arzoxifene 20 mg/day and placebo in 9,354 postmenopausal women with osteoporosis (N=5,252) or low bone mass (N=4,102). Primary outcomes were vertebral fracture in the osteoporotic population and invasive breast cancer in all study participants. Here, we report the detailed breast cancer findings from the trial. Breast cancers were detected by annual mammograms and clinical examination. After 48 months follow-up, breast cancer incidence was compared between treatment groups by estrogen receptor (ER) and progesterone receptor (PR) status and baseline risk factors. Baseline breast cancer risk factors, including age, estimated Gail risk, and bone mineral density, were well balanced between treatment groups. A total of 75 breast cancers occurred 53 in the placebo group and 22 in the arzoxifene group (HR 0.41, 95% CI 0.25-0.68, P<0.001). There were 62 invasive breast cancers, 39 identified as invasive ER-positive (placebo 30, arzoxifene 9; HR 0.30, 95% CI 0.14-0.63, P=0.001) and 30 identified as invasive PR-positive (placebo 23, arzoxifene 7; HR 0.30, 95% CI 0.13-0.71, P=0.003). Breast cancer risk reduction with arzoxifene was similar between Gail risk groups (P interaction=0.31) and between low bone mass and osteoporosis groups (P interaction=0.35). Although generally well tolerated, there was a significant increase in venous thromboembolism, vasomotor symptoms, muscle cramps, and some gynecological events with arzoxifene. These findings demonstrate that in this study arzoxifene reduced the risk of ER-positive breast cancer in this population of postmenopausal women with low bone mass or osteoporosis, an effect similar to that seen with other SERMs.