RESUMO
OBJECTIVES: Flow cytometry with adenosine diphosphate (ADP) allows to characterize molecular changes of platelet function caused by this physiologically important activation, but the methodology has not been thoroughly investigated, standardized and characterized yet. We analyzed the influence of several major variables and chose optimal conditions for platelet function assessment. METHODS: For activation, 2.5 µM CaCl2 , 5 µM ADP and antibodies were added to diluted blood and incubated for 15 min. We analyzed kinetics of antibody binding and effects of their addition sequence, agonist concentration, blood dilution, exogenous calcium addition and platelet fixation. RESULTS: We tested our protocol on 11 healthy children, 22 healthy adult volunteers, 9 patients after a month on dual antiplatelet therapy after percutaneous coronary intervention (PCI), 7 adult patients and 14 children with immune thrombocytopenia (ITP). We found that our protocol is highly sensitive to ADP stimulation with low percentage of aggregates formation. The assay is also sensitive to platelet function inhibition in post-PCI patients. Finally, platelet preactivation with ITP plasma was stronger and caused increase in activation response to ADP stimulation compared to preactivation with low dose of ADP. CONCLUSIONS: Our assay is sensitive to antiplatelet therapy and platelet preactivation in ITP patients under physiological conditions with minimal percentage of aggregates formation.
Assuntos
Intervenção Coronária Percutânea , Púrpura Trombocitopênica Idiopática , Adulto , Criança , Humanos , Citometria de Fluxo/métodos , Plaquetas/metabolismo , Púrpura Trombocitopênica Idiopática/terapia , Púrpura Trombocitopênica Idiopática/tratamento farmacológico , Difosfato de Adenosina/farmacologia , Difosfato de Adenosina/metabolismo , Difosfato de Adenosina/uso terapêutico , Inibidores da Agregação Plaquetária/farmacologia , Inibidores da Agregação Plaquetária/uso terapêutico , Agregação Plaquetária , Ativação PlaquetáriaRESUMO
INTRODUCTION AND AIM: Polymorphic variant rs738409 within the PNPLA3 gene associates with alcoholic liver cirrhosis (ALC) in heavy drinkers of various ancestry but has not yet been established in the Russian population characterized by high incidence of ALC. PNPLA3 rs738409 involvement in the inflammatory process has been proposed as one of the mechanisms of liver dysfunction. Relationship between the PNPLA3 polymorphism and the biochemical markers of inflammation in patients with ALC remains unclear. The current study revealed the association between the rs738409 polymorphism, liver cirrhosis and serum cytokines in heavy drinkers in the Russian population. MATERIALS AND METHODS: The serum levels of IL6, IL10, IL8, and CCL2 along with PNPLA3 rs738409 polymorphism were determined in heavy drinkers (AA, n=71) and heavy drinkers with diagnosed liver cirrhosis (ALC, n=110). All of the recruited individuals were Caucasians and belonged to the Russian population. RESULTS: Heavy drinkers carrying PNPLA3 rs738409 CG or CG+GG genotypes as compared with CC genotype carriers or G allele as compared with C allele carriers had significant risk of ALC. In ALC levels of interleukins and CCL2 increased as compared with AA. PNPLA3 rs738409 CC carriers had lower cirrhosis stage as compared with CG+GG carriers, however there were no differences of IL6, IL10, IL8 or CCL2 levels between G allele carriers and non-carriers in heavy drinkers. CONCLUSION: Thus, in the Russian population heavy drinkers carrying PNPLA3 rs738409 G allele are at higher risk of ALC, however the presence of rs738409 allele does not influence the serum cytokine levels.
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Consumo de Bebidas Alcoólicas/sangue , Consumo de Bebidas Alcoólicas/genética , Quimiocina CCL2/sangue , Interleucinas/sangue , Lipase/genética , Cirrose Hepática Alcoólica/sangue , Cirrose Hepática Alcoólica/genética , Proteínas de Membrana/genética , Polimorfismo Genético/genética , Adulto , Idoso , Feminino , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Federação RussaRESUMO
BACKGROUND: Despite the poor prognosis in patients with type 2 myocardial infarction (MI), no prospective data on risk stratification exists. The aim of this study was to develop and validate a model for prediction of 18-month mortality of among patients with type 2 MI (T2MI) and compare its performance with GRACE and TARRACO scores. METHODS: The prospective observational study included 712 consecutive patients diagnosed with MI undergoing coronary angiography <24 h between January 2017 and December 2018. Diagnosis of T2MI was adjusted according to Third universal definition. A prognostic model was developed by using Bayesian approach and logistic regression analysis with identifying predictors for mortality. The model was validated by bootstrap validation. Comparison performance between scores using Delong test. RESULTS: T2MI was identified in 174 (24.4%) patients. The median age of patients was 69 years, 52% were female. The mortality rate was 20.1% at 18 months. Prior MI, presence of ST elevation, hemoglobin level at admission, Charlson comorbidity index and were independently associated with 18-month mortality. The model to predict 18-month mortality showed excellent discrimination (optimism corrected c-statistic = 0.822) and calibration (corrected slope = 0.893). GRACE and TARRACO scores had moderate discrimination [c-statistic = 0.748 (95% CI 0.652-0.843) and 0.741, 95% CI 0.669-0.805), respectively] and inferior compared with model (p = 0.043 and 0.037, respectively). CONCLUSIONS: The risk of mortality among T2MI patients could be accurately predicted by using common clinical characteristics and laboratory tests. Further studies are required with external validation of nomogram prior to clinical implementation.
Assuntos
Infarto do Miocárdio/diagnóstico , Idoso , Teorema de Bayes , Comorbidade , Angiografia Coronária , Feminino , Hemoglobinas/metabolismo , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Mortalidade , Infarto do Miocárdio/classificação , Infarto do Miocárdio/metabolismo , Infarto do Miocárdio sem Supradesnível do Segmento ST/classificação , Infarto do Miocárdio sem Supradesnível do Segmento ST/diagnóstico , Infarto do Miocárdio sem Supradesnível do Segmento ST/metabolismo , Reprodutibilidade dos Testes , Infarto do Miocárdio com Supradesnível do Segmento ST/classificação , Infarto do Miocárdio com Supradesnível do Segmento ST/diagnóstico , Infarto do Miocárdio com Supradesnível do Segmento ST/metabolismoRESUMO
BACKGROUND: Experimental and clinical data suggest that reducing inflammation without affecting lipid levels may reduce the risk of cardiovascular disease. Yet, the inflammatory hypothesis of atherothrombosis has remained unproved. METHODS: We conducted a randomized, double-blind trial of canakinumab, a therapeutic monoclonal antibody targeting interleukin-1ß, involving 10,061 patients with previous myocardial infarction and a high-sensitivity C-reactive protein level of 2 mg or more per liter. The trial compared three doses of canakinumab (50 mg, 150 mg, and 300 mg, administered subcutaneously every 3 months) with placebo. The primary efficacy end point was nonfatal myocardial infarction, nonfatal stroke, or cardiovascular death. RESULTS: At 48 months, the median reduction from baseline in the high-sensitivity C-reactive protein level was 26 percentage points greater in the group that received the 50-mg dose of canakinumab, 37 percentage points greater in the 150-mg group, and 41 percentage points greater in the 300-mg group than in the placebo group. Canakinumab did not reduce lipid levels from baseline. At a median follow-up of 3.7 years, the incidence rate for the primary end point was 4.50 events per 100 person-years in the placebo group, 4.11 events per 100 person-years in the 50-mg group, 3.86 events per 100 person-years in the 150-mg group, and 3.90 events per 100 person-years in the 300-mg group. The hazard ratios as compared with placebo were as follows: in the 50-mg group, 0.93 (95% confidence interval [CI], 0.80 to 1.07; P=0.30); in the 150-mg group, 0.85 (95% CI, 0.74 to 0.98; P=0.021); and in the 300-mg group, 0.86 (95% CI, 0.75 to 0.99; P=0.031). The 150-mg dose, but not the other doses, met the prespecified multiplicity-adjusted threshold for statistical significance for the primary end point and the secondary end point that additionally included hospitalization for unstable angina that led to urgent revascularization (hazard ratio vs. placebo, 0.83; 95% CI, 0.73 to 0.95; P=0.005). Canakinumab was associated with a higher incidence of fatal infection than was placebo. There was no significant difference in all-cause mortality (hazard ratio for all canakinumab doses vs. placebo, 0.94; 95% CI, 0.83 to 1.06; P=0.31). CONCLUSIONS: Antiinflammatory therapy targeting the interleukin-1ß innate immunity pathway with canakinumab at a dose of 150 mg every 3 months led to a significantly lower rate of recurrent cardiovascular events than placebo, independent of lipid-level lowering. (Funded by Novartis; CANTOS ClinicalTrials.gov number, NCT01327846 .).
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Anti-Inflamatórios/administração & dosagem , Anticorpos Monoclonais/administração & dosagem , Aterosclerose/tratamento farmacológico , Interleucina-1beta/antagonistas & inibidores , Infarto do Miocárdio/tratamento farmacológico , Idoso , Anti-Inflamatórios/efeitos adversos , Anticorpos Monoclonais/efeitos adversos , Anticorpos Monoclonais Humanizados , Aterosclerose/sangue , Proteína C-Reativa/metabolismo , Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/mortalidade , Relação Dose-Resposta a Droga , Método Duplo-Cego , Feminino , Humanos , Incidência , Infecções/etiologia , Interleucina-1beta/imunologia , Lipídeos/sangue , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/prevenção & controle , Neutropenia/induzido quimicamente , Prevenção Secundária , Acidente Vascular Cerebral/prevenção & controleRESUMO
PURPOSE OF REVIEW: The management of individuals who live with type 2 diabetes requires an integrated and multifaceted approach. RECENT FINDINGS: Sodium-glucose cotransporter 2 inhibitors effectively prevent and treat cardiorenal complications in the presence of type 2 diabetes. They also reduce death and disease progression in those with established heart failure (with reduced ejection fraction) in the absence of diabetes. SUMMARY: Close collaborations between primary care physicians, cardiovascular specialists, endocrinologists and nephrologists are necessary to optimize cardiovascular, renal and metabolic risk reduction in their shared patients.
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Doenças Cardiovasculares , Diabetes Mellitus Tipo 2 , Inibidores do Transportador 2 de Sódio-Glicose , Glicemia , Doenças Cardiovasculares/prevenção & controle , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/tratamento farmacológico , Humanos , Hipoglicemiantes , Assistência Centrada no Paciente , Sódio , Inibidores do Transportador 2 de Sódio-Glicose/uso terapêuticoRESUMO
OBJECTIVE: The significance of liver stiffness (LS) in the setting of cardiovascular congestion during the course of acute decompensated heart failure (ADHF) is under investigation. The aim of this study was to assess LS with the use of transient elastography (TE) and its associations with volume overload as determined by means of bioimpedance vector analysis (BIVA) in ADHF. METHODS AND RESULTS: TE (Fibroscan 502; Echosens) and BIVA (ABC-01, Medass) were performed in the first 48 hours of admission and on the day of discharge in 149 ADHF patients without known primary chronic liver disease or acute hepatitis. During hospitalization the median value of LS decreased from 12.2 kPa (interquartile range 6.3-23.6) to 8.7 (5.9-14.4) kPa (P < .001). Changes in LS correlated (P < .001) with changes in weight and BIVA parameters. LS was compared with histologic features of livers of ADHF patients who died (nâ¯=â¯7). Liver fibrosis 2B-4 was observed but was not associated with LS. LS at discharge was associated with increased risk of 12-month all-cause death, HF readmission, and the combined end point. CONCLUSIONS: There was a moderate association between LS with clinical congestion and volume overload according to BIVA and no correlation with degree of histologic liver fibrosis. LS may be a marker of negative HF outcomes.
Assuntos
Insuficiência Cardíaca/diagnóstico por imagem , Insuficiência Cardíaca/epidemiologia , Cirrose Hepática/diagnóstico por imagem , Cirrose Hepática/epidemiologia , Doença Aguda , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos ProspectivosRESUMO
Mitogen-activated protein kinase p38 is a key regulator in the inflammation pathway and is activated in the lungs of chronic obstructive pulmonary disease (COPD) patients. Acumapimod is a potent, selective, oral, p38 inhibitor under investigation for treatment of acute exacerbations of COPD (AECOPD). In this Phase II, double-blind, randomized, placebo-controlled dose-exploration study of acumapimod in patients with moderate or severe AECOPD (NCT01332097), patients presenting with AECOPD were randomized to receive single-dose acumapimod (20 mg or 75 mg) on Day 1, repeated single-dose acumapimod (20 mg or 75 mg) on Days 1 and 6, oral prednisone 40 mg (10 days), or placebo. Primary outcome: improvement in forced expiratory volume in 1 s (FEV1) versus placebo at Day 5 (single doses) and Day 10 (repeated doses). N = 183 patients were randomized; 169 (92%) patients completed the study. Although the primary endpoint (FEV1 at Day 10) was not met (p = 0.082), there was a significant improvement in FEV1 with acumapimod repeat-dose 75 mg versus placebo at Day 8 (p = 0.022) which, though not a prespecified endpoint, was part of an overall trend. Differences at lower doses did not achieve significance. Mean change in FEV1 AUC from baseline to Day 14 in the 75 mg repeat-dose group was significantly higher versus placebo (p = 0.02), prednisone (p = 0.01), and 20 mg single-dose groups (p = 0.015) (post-hoc analysis). EXACT-PRO showed numerical differences versus placebo that did not reach significance. Acumapimod was well tolerated. In conclusion, repeated single-dose acumapimod showed a clinically relevant improvement in FEV1 over placebo at Day 8, along with consistent numerical differences in EXACT-PRO. These data can be used to determine dose regimens for a proof-of-clinical-concept trial.
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Anti-Inflamatórios/administração & dosagem , Benzamidas/administração & dosagem , Doença Pulmonar Obstrutiva Crônica/tratamento farmacológico , Pirazóis/administração & dosagem , Proteínas Quinases p38 Ativadas por Mitógeno/antagonistas & inibidores , Adulto , Idoso , Progressão da Doença , Método Duplo-Cego , Esquema de Medicação , Feminino , Seguimentos , Volume Expiratório Forçado , Humanos , Masculino , Pessoa de Meia-Idade , Índice de Gravidade de Doença , Resultado do TratamentoRESUMO
AIMS: Human cytomegalovirus constitutes a prevalent and serious threat to immunocompromised individuals and requires new treatments. Letermovir is a novel viral-terminase inhibitor that has demonstrated prophylactic/pre-emptive activity against human cytomegalovirus in Phase 2 and 3 transplant trials. As unchanged letermovir is primarily excreted via the liver by bile, this trial aimed to assess the effect of hepatic impairment on letermovir pharmacokinetics. METHODS: Phase 1, open-label, parallel-group pharmacokinetic and safety comparison of multiple once-daily oral letermovir in female subjects with hepatic impairment and healthy matched controls. For 8 days, subjects with moderate hepatic impairment (n = 8) and their matched healthy controls (n = 9) received 60 mg letermovir/day and those with severe hepatic impairment (n = 8) and their matched healthy controls (n = 8) received 30 mg letermovir/day. Pharmacokinetic parameters were determined from blood samples. RESULTS: For subjects with moderate hepatic impairment, maximal observed concentration at steady state (Css,max ) and the area under the concentration vs. time curve over a dosing interval at steady state (AUCτ,ss ) for total letermovir were 1.37-fold (90% confidence interval: 0.87, 2.17) and 1.59-fold (0.98, 2.57) higher, respectively, than in healthy subjects. For subjects with severe hepatic impairment, Css,max and AUCτ,ss values of total letermovir were 2.34-fold (1.91, 2.88) and 3.82-fold (2.94, 4.97) higher, respectively, compared with healthy subjects. CONCLUSIONS: Moderate hepatic impairment increased exposure to letermovir <2-fold, while severe hepatic impairment increased letermovir exposure approximately 4-fold as compared with healthy subjects. Letermovir 60/30 mg/day was generally well-tolerated in subjects with hepatic impairment.
Assuntos
Acetatos/farmacocinética , Antivirais/farmacocinética , Infecções por Citomegalovirus/tratamento farmacológico , Hepatopatias/metabolismo , Fígado/metabolismo , Quinazolinas/farmacocinética , Acetatos/administração & dosagem , Acetatos/efeitos adversos , Acetatos/sangue , Administração Oral , Adolescente , Adulto , Idoso , Antivirais/administração & dosagem , Antivirais/efeitos adversos , Antivirais/sangue , Área Sob a Curva , Esquema de Medicação , Feminino , Meia-Vida , Humanos , Fígado/fisiopatologia , Hepatopatias/diagnóstico , Hepatopatias/fisiopatologia , Taxa de Depuração Metabólica , Pessoa de Meia-Idade , Quinazolinas/administração & dosagem , Quinazolinas/efeitos adversos , Quinazolinas/sangue , Federação Russa , Índice de Gravidade de Doença , Resultado do Tratamento , Adulto JovemAssuntos
Síndrome Coronariana Aguda/tratamento farmacológico , Anticoagulantes/uso terapêutico , Aspirina/uso terapêutico , Fibrilação Atrial/tratamento farmacológico , Fármacos Cardiovasculares/uso terapêutico , Fibrinolíticos/uso terapêutico , Hospitalização/estatística & dados numéricos , Intervenção Coronária Percutânea , Inibidores da Agregação Plaquetária/uso terapêutico , Pirazóis/uso terapêutico , Piridonas/uso terapêutico , Síndrome Coronariana Aguda/complicações , Síndrome Coronariana Aguda/cirurgia , Idoso , Anticoagulantes/efeitos adversos , Fibrilação Atrial/complicações , Terapia Combinada , Quimioterapia Combinada , Procedimentos Cirúrgicos Eletivos , Feminino , Fibrinolíticos/efeitos adversos , Hemorragia/induzido quimicamente , Hemorragia/epidemiologia , Humanos , Tempo de Internação/estatística & dados numéricos , Masculino , Pessoa de Meia-Idade , Estudos Multicêntricos como Assunto/estatística & dados numéricos , Inibidores da Agregação Plaquetária/efeitos adversos , Modelos de Riscos Proporcionais , Estudos Prospectivos , Antagonistas do Receptor Purinérgico P2Y/efeitos adversos , Antagonistas do Receptor Purinérgico P2Y/uso terapêutico , Ensaios Clínicos Controlados Aleatórios como Assunto/estatística & dados numéricos , Análise de Sobrevida , Resultado do Tratamento , Vitamina K/antagonistas & inibidoresRESUMO
AIMS: Serelaxin is a recombinant form of human relaxin-2 in development for treatment of acute heart failure. This study aimed to evaluate the pharmacokinetics (PK) of serelaxin in patients with hepatic impairment. Secondary objectives included evaluation of immunogenicity, safety and tolerability of serelaxin. METHODS: This was an open-label, parallel group study (NCT01433458) comparing the PK of serelaxin following a single 24 h intravenous (i.v.) infusion (30 µg kg(-1) day(-1) ) between patients with mild, moderate or severe hepatic impairment (Child-Pugh class A, B, C) and healthy matched controls. Blood sampling and standard safety assessments were conducted. Primary non-compartmental PK parameters [including area under the serum concentration-time curve AUC(0-48 h) and AUC(0-∞) and serum concentration at 24 h post-dose (C24h )] were compared between each hepatic impairment group and healthy controls. RESULTS: A total of 49 subjects (including 25 patients with hepatic impairment) were enrolled, of which 48 subjects completed the study. In all groups, the serum concentration of serelaxin increased over the first few hours of infusion, reached steady-state at 12-24 h and then declined following completion of infusion, with a mean terminal half-life of 7-8 h. All PK parameter estimates were comparable between each group of patients with hepatic impairment and healthy controls. No serious adverse events, discontinuations due to adverse events or deaths were reported. No serelaxin treatment-related antibodies developed during this study. CONCLUSIONS: The PK and safety profile of serelaxin were not affected by hepatic impairment. No dose adjustment is needed for serelaxin treatment of 48 h i.v. infusion in patients with hepatic impairment.
Assuntos
Fármacos Cardiovasculares/farmacocinética , Hepatopatias/metabolismo , Fígado/metabolismo , Relaxina/farmacocinética , Área Sob a Curva , Fármacos Cardiovasculares/administração & dosagem , Fármacos Cardiovasculares/efeitos adversos , Fármacos Cardiovasculares/sangue , Esquema de Medicação , Feminino , Alemanha , Humanos , Infusões Intravenosas , Fígado/fisiopatologia , Hepatopatias/sangue , Hepatopatias/diagnóstico , Hepatopatias/fisiopatologia , Testes de Função Hepática , Masculino , Taxa de Depuração Metabólica , Pessoa de Meia-Idade , Modelos Biológicos , Proteínas Recombinantes/administração & dosagem , Proteínas Recombinantes/efeitos adversos , Proteínas Recombinantes/sangue , Proteínas Recombinantes/farmacocinética , Relaxina/administração & dosagem , Relaxina/efeitos adversos , Relaxina/sangue , Federação Russa , Índice de Gravidade de DoençaRESUMO
OBJECTIVE: This study assessed the pharmacokinetics and tolerability of fingolimod and its metabolites in severe renal impairment and healthy subjects. METHODS: In this single-dose, open-label study, 9 severe renal impairment subjects and 9 demographically matched healthy subjects were included. Each subject received a single oral dose of fingolimod 1.25 mg, and their blood and urine samples were assessed. The pharmacokinetics of fingolimod and its metabolites, fingolimod-phosphate (active metabolite, fingolimod-P), M2, and M3, were compared in both groups. Safety and tolerability were also assessed. RESULTS: In severe renal impairment subjects, mean±standard deviation values of Cmax (ng/mL) of fingolimod and fingolimod-P were 0.878±0.256 and 1.13±0.293 vs. 0.653±0.138 and 0.904±0.229 in healthy subjects, respectively. The overall drug exposures (AUCinf (ngxh/mL)) for fingolimod and fingolimod-P were 131±90.7 and 75.5±33.6 in severe renal impairment subjects vs. 82.3±36.9 and 65.9±30.6 in healthy subjects, respectively. t1/2 (hours) for fingolimod and fingolimod-P was comparable in severe renal impairment subjects (94±53 and 95±50) and healthy subjects (85±25 and 101±46). All adverse events were as expected for fingolimod 1.25 mg. CONCLUSIONS: The exposure to fingolimod and fingolimod-P was moderately increased (90% CI, 0.94-2.18) in severe renal impairment subjects, while half-lives and protein binding were similar to those in healthy subjects. Given that these changes are not clinically meaningful, fingolimod dose adjustment is considered unnecessary in patients with mild, moderate, or severe renal impairment.
Assuntos
Cloridrato de Fingolimode/farmacocinética , Insuficiência Renal/metabolismo , Adulto , Feminino , Cloridrato de Fingolimode/efeitos adversos , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
INTRODUCTION: The present real-world analysis aims to compare the drug utilization, hospitalizations and direct healthcare costs related to the use of single-pill combination (SPC) or free-equivalent combination (FEC) of perindopril and bisoprolol (PER/BIS) in a large Italian population. METHODS: This observational retrospective analysis was based on administrative databases covering approximately 7 million subjects across Italy. All adult subjects receiving PER/BIS as SPC or FEC between January 2017-June 2020 were included. Subjects were followed for 1 year after the first prescription of PER/BIS as FEC (± 1 month) or SPC. Before comparing the SPC and FEC cohorts, propensity score matching (PSM) was applied to balance the baseline characteristics. Drug utilization was investigated as adherence (defined by the proportion of days covered, PDC) and persistence (evaluated by Kaplan-Meier curves). Hospitalizations and mean annual direct healthcare costs (due to drug prescriptions, hospitalizations and use of outpatient services) were analyzed during follow-up. RESULTS: The original cohort included 11,440 and 6521 patients taking the SPC and FEC PER/BIS combination, respectively. After PSM, two balanced SPC and FEC cohorts of 4688 patients were obtained (mean age 70 years, approximately 50% male, 24% in secondary prevention). The proportion of adherent patients (PDC ≥ 80%) was higher for those on SPC (45.5%) than those on FEC (38.6%), p < 0.001. The PER/BIS combination was discontinued by 35.8% of patients in the SPC cohort and 41.7% in the FEC cohort (p < 0.001). The SPC cohort had fewer cardiovascular (CV) hospitalizations (5.3%) than the free-combination cohort (7.4%), p < 0.001. Mean annual total healthcare costs were lower in the SPC (1999) than in the FEC (2359) cohort (p < 0.001). CONCLUSION: In a real-world setting, patients treated with PER/BIS SPC showed higher adherence, lower risk of drug discontinuation, reduced risk of CV hospitalization, and lower healthcare costs than those on FEC of the same drugs.
Patients with cardiovascular conditions often need to take many pills. This may result in patients not taking their pills as prescribed (i.e., low adherence) and compromise the potential benefits derived from prescription of cardiovascular protective drugs. Simplifying treatment by combining drugs into a single pill can improve adherence and, consequently, patient outcomes. In this analysis using data from real clinical practice, we explored whether using a single pill of perindopril and bisoprolol is associated with higher levels of adherence, lower proportion of patients with hospitalizations and lower economic costs than using the same drugs prescribed as free-equivalent combination in a large sample of the Italian population of approximately 7 million people. We identified two groups of patients taking single pill or free-equivalent combination of perindopril and bisoprolol (4688 patients in each cohort). Over 1-year follow-up, patients taking single pill were more likely to be adherent and were less likely to stop taking their treatment. They also had fewer cardiovascular hospitalizations with shorter hospital admission and had lower healthcare direct costs. In conclusion, simplifying treatment by combining perindopril and bisoprolol in a single pill instead of two may have a positive effect on adherence, outcomes and healthcare costs already after 1 year.
Assuntos
Hipertensão , Perindopril , Adulto , Humanos , Masculino , Idoso , Feminino , Perindopril/uso terapêutico , Anti-Hipertensivos/uso terapêutico , Hipertensão/tratamento farmacológico , Bisoprolol/uso terapêutico , Estudos Retrospectivos , Atenção à Saúde , Adesão à MedicaçãoRESUMO
Diabetes mellitus (DM) is considered by many the pandemic of the 21st century and is associated with multiple organ damages. Among these, cardiovascular complications are responsible for an incredible burden of mortality and morbidity in Western Countries. The study of the pathological mechanisms responsible for the cardiovascular complications in DM patients is key for the development of new therapeutic strategies. The metabolic disorders caused by hyperglycemia, insulin resistance, and dyslipidemia, results in a cascade of pathomorphological changes favoring the atherosclerotic process and leading to myocardial remodeling. Parallel to this, oxidative stress, calcium overload, mitochondrial dysfunction, activation of protein kinase C signaling pathways, myocardial lipomatosis, and low-grade inflammation of the myocardium - are the main pathways responsible for the diabetic cardiomyopathy development. This review aims to appraise and discuss the pathogenetic mechanisms behind the diabetic cardiomyopathy development.
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Diabetes Mellitus , Cardiomiopatias Diabéticas , Humanos , Cardiomiopatias Diabéticas/etiologia , Cardiomiopatias Diabéticas/terapia , Miocárdio/metabolismo , Estresse Oxidativo , Transdução de SinaisRESUMO
INTRODUCTION: This study assessed the real-life effectiveness of a single-pill combination (SPC) of bisoprolol/perindopril for controlling blood pressure (BP) and symptoms of angina in patients with hypertension and a history of myocardial infarction (MI). METHODS: Eligible patients with arterial hypertension and a history of MI were aged 18-79 years and had initiated bisoprolol/perindopril SPC within 3 months of study enrollment as part of routine Russian clinical practice. The primary endpoint was mean change in systolic and diastolic BP (SBP/DBP) at week 12 compared with baseline (data collected retrospectively). Secondary endpoints were assessed at weeks 4 and 12 and included mean change in resting heart rate (HR), proportion of patients reaching target level of resting HR, antianginal effectiveness of the SPC, and proportion of patients reaching target BP levels. RESULTS: A total of 504 patients were enrolled, of whom 481 comprised the full analysis set (mean age 61.4 ± 8.9 years, 68% men). Mean baseline SBP/DBP and HR values were 148.9 ± 16.8/87.7 ± 11.0 mmHg and 77.4 ± 10.5 bpm, respectively. Mean durations of hypertension and CAD were 12.8 ± 8.4 and 6.1 ± 6.3 years, respectively, and time since MI was 3.8 ± 5.3 years. At week 12, SBP/DBP had decreased by 24.9/12.2 mmHg (P < 0.001 vs baseline). Target BP (< 140/90 mmHg) was achieved by 69.8% and 95.9% of patients at weeks 4 and 12, respectively, and target HR (55-60 bpm) by 17.3% and 34.5% at weeks 4 and 12 versus 3.1% at baseline (P < 0.001). Reductions in angina attacks, nitrate consumption, and improvements in HR were statistically significant. Treatment was well tolerated. CONCLUSION: Treatment of symptomatic patients with CAD, hypertension, and a history of MI with a bisoprolol/perindopril SPC was associated with significant decreases in SBP/DBP and a high proportion of patients achieving BP treatment goals. This was accompanied by improvements in angina symptoms and reductions in HR in a broad patient population representative of those seen in everyday clinical practice. TRIAL REGISTRATION: ClinicalTrials.gov Identifier NCT04656847.
Assuntos
Hipertensão , Infarto do Miocárdio , Masculino , Humanos , Pessoa de Meia-Idade , Idoso , Feminino , Perindopril/efeitos adversos , Bisoprolol/efeitos adversos , Anti-Hipertensivos/efeitos adversos , Estudos Retrospectivos , Hipertensão/complicações , Hipertensão/tratamento farmacológico , Pressão Sanguínea , Infarto do Miocárdio/complicações , Infarto do Miocárdio/tratamento farmacológico , Angina Pectoris , Combinação de Medicamentos , Resultado do TratamentoRESUMO
Objectives: The Rajan's heart failure (R-hf) score was proposed to aid risk stratification in heart failure patients. The aim of this study was to validate R-hf risk score in patients with acute decompensated heart failure. Methods: R-hf risk score is derived from the product estimated glomerular filtration rate (mL/min), left ventricular ejection fraction (%), and hemoglobin levels (g/dL) divided by N-terminal pro-brain natriuretic peptide (pg/mL). This was a multinational, multicenter, prospective registry of heart failure from seven countries in the Middle East. Univariable and multivariable logistic regression was applied. Results: A total of 776 patients (mean age = 62.0±14.0 years, 62.4% males; mean left ventricular ejection fraction = 33.0±14.0%) were included. Of these, 459 (59.1%) presented with acute decompensated chronic heart failure. The R-hf risk score group (≤ 5) was marginally associated with a higher risk of all-cause cumulative mortality at three months (adjusted odds ratio (aOR) = 4.28; 95% CI: 0.90-20.30; p =0.067) and significantly at 12 months (aOR = 3.84; 95% CI: 1.23-12.00; p =0.021) when compared to those with the highest R score group (≥ 50). Conclusions: Lower R-hf risk scores are associated with increased risk of all-cause cumulative mortality at three and 12 months.
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The infection caused by the Human Immunodeficiency Virus (HIV) has spread rapidly across the globe, assuming the characteristics of an epidemic in some regions. Thanks to the introduction of antiretroviral therapy into routine clinical practice, there was a considerable breakthrough in the treatment of HIV, that is now HIV is potentially well-controlled even in low-income countries. To date, HIV infection has moved from the group of life-threatening conditions to the group of chronic and well controlled ones and the quality of life and life expectancy of HIV+ people, with an undetectable viral load is closer to that of an HIV- people. However, unsolved issues still persist. For example: people living with HIV are more prone to the age-related diseases, especially atherosclerosis. For this reason, a better understanding of the mechanisms of HIV-associated destabilization of vascular homeostasis seems to be an urgent duty, that may lead to the development of new protocols, bringing the possibilities of pathogenetic therapies to a new level. The purpose of the article was to evaluate the pathological aspects of HIV-induced atherosclerosis.
Assuntos
Infecções por HIV , HIV , Humanos , Infecções por HIV/complicações , Infecções por HIV/tratamento farmacológico , Infecções por HIV/epidemiologia , Terapia Antirretroviral de Alta Atividade , Qualidade de VidaRESUMO
Aims: Cardiac device-related infective endocarditis (CDRIE) is a severe complication of cardiac device (CD) implantation and is usually treated by antibiotic therapy and percutaneous device extraction. Few studies report the management and prognosis of CDRIE in real life. In particular, the rate of device extraction in clinical practice and the management of patients with left heart infective endocarditis (LHIE) and an apparently non-infected CD (LHIE+CDRIE-) are not well described. Methods and results: We sought to study in EURO-ENDO, the characteristics, prognosis, and management of 483 patients with a CD included in the European Society of Cardiology EurObservational Research Programme EURO-ENDO registry. Three populations were compared: 280 isolated CDRIE (66.7 ± 14.3 years), 157 patients with LHIE and an apparently non-infected CD (LHIE+CDRIE-) (71.1 ± 13.6), and 46 patients with both LHIE and CDRIE (LHIE+CDRIE+) (70.2 ± 10.1). Echocardiography was not always transoesophageal echography (TOE); it was transthoracic echography (TTE) for isolated CDRIE in 88.4% (TOE = 67.6%), for LHIE+CDRIE- TTE = 93.0% (TOE = 58.6%), and for CDRIE+LHIE+ TTE = 87.0% (TOE = 63.0%). Nuclear imaging was performed in 135 patients (positive for 75.6%). In-hospital mortality was lower in isolated CDRIE 13.2% vs. 22.3% and 30.4% for LHIE+CDRIE- and LHIE+CDRIE+ (P = 0004). Device extraction was performed in 62.1% patients with isolated CDRIE, 10.2% of LHIE+CDRIE- patients, and 45.7% of CDRIE+LHIE+ patients. Device extraction was associated with a better prognosis [hazard ratio 0.59 (0.40-0.87), P = 0.0068] even in the LHIE+CDRIE- group (P = 0.047). Conclusion: Prognosis of endocarditis in patients with a CD remains poor, particularly in the presence of an associated LHIE. Although recommended by guidelines, device extraction is not always performed. Device removal was associated with better prognosis, even in the LHIE+CDRIE- group.
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This study aimed to evaluate the clinical outcomes of patients with acute heart failure (AHF) stratified by mitral regurgitation (MR) in the Arabian Gulf. Patients from the Gulf CARE registry were identified from 47 hospitals in seven Arabian Gulf countries (Yemen, Oman, Kuwait, Qatar, Bahrain, the United Arab Emirates, and Saudi Arabia) from February to November 2012. The cohort was stratified into two groups based on the presence of MR. Univariable and multivariable statistical analyses were performed. The population cohort included 5005 consecutive patients presenting with AHF, of whom 1491 (29.8 %) had concomitant MR. The mean age of patients with AHF and concomitant MR was 59.2 ± 14.9 years, and 63.1 % (n = 2886) were male. A total of 58.6 % (n = 2683) had heart failure (HF) with reduced ejection fraction (EF) (HFrEF), 21.0 % (n = 961) had HF with mildly reduced EF (HFmrEF), and 20.4 % (n = 932) had HF with preserved EF (HFpEF). Patients with MR had a lower haemoglobin (Hb) level (12.4 vs. 12.7 g/dL; p < 0.001), and a higher prevalence of left atrial enlargement (80.2 % vs. 55.1 %; p < 0.001), cardiogenic shock (9.7 % vs. 7.3 %; p = 0.006) and atrial fibrillation (7.6 % vs. 5.6 %; p = 0.006), and HFrEF (71.0 % vs. 52.6 %; P < 0.001). Multivariable analysis demonstrated that MR was independently associated with increased all-cause mortality at 1-year and 3-month HF rehospitalization [1-year all-cause mortality, adjusted odds ratio (aOR), 1.40; 95 % confidence interval (Cl): 1.13-1.74; p = 0.002; 3-month HF rehospitalization, aOR, 1.26; 95 % Cl: 1.06-1.49; p = 0.009]. In an Arabian Gulf cohort with AHF, concomitant MR was associated with an increased risk of 1-year mortality and 3-months HF rehospitalization.
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Objectives: Initial reports indicate a high incidence of abnormal aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels in patients with COVID-19 and possible association with acute kidney injury (AKI). We aimed to investigate clinical features of elevated transaminases on admission, its association with AKI, and outcomes in patients with COVID-19. Methods: A retrospective analysis of the registered data of hospitalized patients with laboratory-confirmed COVID-19 and assessment of the AST and ALT was performed. Multinomial logistic regression was used to determine factors associated with community-acquired AKI (CA-AKI) and hospital-acquired AKI (HA-AKI). Results: The subjects comprised 828 patients (mean age = 65.0±16.0 years; 51.4% male). Hypertension was present in 70.3% of patients, diabetes mellitus in 26.0%, and chronic kidney disease in 8.5%. In-hospital mortality was 21.0%. At admission, only 41.5% of patients had hypertransaminasemia. Patients with elevated transaminases at admission were younger, had higher levels of inflammatory markers and D-dimer, and poorer outcomes. The AKI incidence in the study population was 27.1%. Patients with hypertransaminasemia were more likely to develop AKI (33.5% vs. 23.3%, p = 0.003). Patients with predominantly elevated AST (compared to elevated ALT) were more likely to have adverse outcomes. Multinomial logistic regression found that hypertension, chronic kidney disease, elevated AST, and hematuria were associated with CA-AKI. Meanwhile, age > 65 years, hypertension, malignancy, elevated AST, and hematuria were predictors of HA-AKI. Conclusions: Elevated transaminases on admission were associated with AKI and poor outcomes. Patients with elevated AST were more likely to have adverse outcomes. Elevated AST on admission was associated with CA-AKI and was a predictor of HA-AKI.
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Background: The aim of this study was to validate R-heart failure (R-hf) risk score in ischemic heart failure patients. Methods: We prospectively recruited a cohort of 179 ischemic and 107 non-ischemic heart failure patients. This study mainly focused on ischemic heart failure patients. Non-ischemic heart failure patients were included for the purpose of validation of the risk score in various heart failure groups. Patients were stratified in high risk, moderate risk and low risk groups according to R-hf risk score. Results: A total of 179 participants with ischemic heart failure were included. Based on R-hf risk score, 82 had high risk, 50 had moderate risk and 47 had low risk heart failure scores. More than half of the patients having R-hf score of <5 had renal failure (n = 91, 50.8%) and anemia (n = 99, 55.3%). Notably, HFrEF was more prevalent in patients with high risk score (74, 90.2%). Patients with high risk score had significantly higher creatinine (2.63 ± 1.96, p < 0.001), Troponin-T HS (59.9 ± 38.0, p < 0.001) and PRO BNP (17842 ± 6684, p < 0.001) when compared to patients with low and moderate risk score. Patients with low risk score had significantly higher Hb (13.2 ± 1.85, p < 0.001), Albumin (3.69 ± 0.42, p < 0.001) and GFR (90.0 ± 8.04, p < 0.001). A R-hf score of <5 was a significant predictor of mortality in ischemic (OR = 50.34; 95% CI [16.94-194.00, p < 0.001) and non-ischemic (OR = 46.34; 95% CI [12.97-225.39], p < 0.001) heart failure patients. Conclusions: Lower R-hf risk score is a significant predictor of mortality in ischemic and non-ischemic heart failure patients. Risk score can be accessed at https://www.hfriskcalc.in.