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1.
J Stroke Cerebrovasc Dis ; 31(9): 106683, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-35914511

RESUMO

OBJECTIVE: Whether aspirin platelet reactivity affects platelet function and clinical outcomes with different antiplatelet therapies in patients with mild stroke or transient ischemic attack (TIA) remains unclear. We conducted a subgroup analysis of the PRINCE trial. MATERIALS AND METHODS: Patients with mild stroke or TIA were randomized into aspirin+ticagrelor, or aspirin+clopidogrel groups; aspirin reaction units (ARU) were measured at the baseline and after 7 ± 2 days to assess response to treatment. High on-treatment platelet reactivity (HPR) was defined as ≥550 ARU (poor response to aspirin). The platelet functions of ticagrelor and clopidogrel were measured using the VerifyNow P2Y12 assay for P2Y12 reaction units (PRU); HPR to P2Y12 was defined as >208 PRU (poor response to P2Y12). Clinical outcomes included stroke and clinical vascular and bleeding events after 90 days. RESULTS: Among 628 enrolled patients, 69 (11%) were poor aspirin responders. After 7 ± 2 days, the proportion of poor P2Y12 responders for ticagrelor versus clopidogrel significantly reduced in poor (2.6% versus 27.4%) and good (14.3% versus 29.4%) aspirin responders. There were significant interactions between treatment groups, and between treatment groups and aspirin platelet reactivity for poor P2Y12 responders (P = 0.01). After 90 ± 7 days, there were no significant interactions between treatment groups and aspirin platelet reactivity for new stroke risk (good aspirin responders: 5.5% versus 8.8%, hazard ratio [HR]: 0.61; 95% confidence interval [CI], 0.32 to 1.16; P = 0.13; poor aspirin responders: 8.6% versus 8.8%, HR: 0.97, 95% CI: 0.20-4.81; P = 0.97; P for interaction = 0.60). Major bleeding was less frequent in poor than good aspirin responders (ticagrelor/aspirin: 0.4%/0%; clopidogrel/aspirin: 1.4%/0%). CONCLUSIONS: In patients with minor stroke or TIA, clopidogrel, and particularly ticagrelor, decreased platelet function in poor versus good aspirin responders. The poor platelet reactivity of aspirin could not sufficiently reduce the risk of recurrent stroke with ticagrelor or clopidogrel; however, HPR (poor aspirin response) may have a protective effect on clinically relevant major bleeding.


Assuntos
Ataque Isquêmico Transitório , Acidente Vascular Cerebral , Aspirina/efeitos adversos , Clopidogrel/efeitos adversos , Quimioterapia Combinada , Humanos , Ataque Isquêmico Transitório/induzido quimicamente , Ataque Isquêmico Transitório/diagnóstico , Ataque Isquêmico Transitório/tratamento farmacológico , Inibidores da Agregação Plaquetária/efeitos adversos , Acidente Vascular Cerebral/induzido quimicamente , Acidente Vascular Cerebral/diagnóstico , Acidente Vascular Cerebral/tratamento farmacológico , Ticagrelor/efeitos adversos , Resultado do Tratamento
2.
J Am Heart Assoc ; 11(17): e025958, 2022 Sep 06.
Artigo em Inglês | MEDLINE | ID: mdl-36000434

RESUMO

Background Real-world data on low baseline low-density lipoprotein cholesterol (LDL-C) levels and long-term postdischarge cardiovascular outcomes in patients with acute coronary syndrome are limited. Methods and Results Of the 10 719 patients enrolled in the Korean registry of acute myocardial infarction between January 2004 and August 2014, we identified 5532 patients who were event free from death, recurrent myocardial infarction, or stroke during the in-hospital period after successful percutaneous coronary intervention. The co-primary outcomes were 3-point major adverse cardiovascular events (a composite of nonfatal stroke, nonfatal myocardial infarction, and cardiovascular death) and cardiovascular death at 5 years. Of 5532 patients with acute myocardial infarction (mean age, 62.1±12.8 years; 75.0% men), 446 cardiovascular deaths (8.1%) and 695 three-point major adverse cardiovascular events (12.6%) occurred at 5 years. In the continuous analysis of LDL-C, the risk of cardiovascular events increased steeply as LDL-C levels decreased from 100 mg/dL. For categorical analysis of LDL-C (<70, 70-99, and ≥100 mg/dL), as LDL-C levels decreased, clinical outcomes worsened (237/3759 [6.3%] in LDL-C ≥100 mg/dL versus 123/1291 [9.5%] in LDL-C 70-99 mg/dL versus 86/482 [17.8%] in LDL-C <70 mg/dL for cardiovascular death; P-trend<0.001; and 417/3759 [11.1%] in LDL-C ≥100 mg/dL versus 172/1291 [13.3%] in LDL-C 70-99 mg/dL versus 106/482 [22.2%] in LDL-C <70 mg/dL for 3-point major adverse cardiovascular event; P-trend<0.001). In a Cox time-to-event multivariable model with LDL-C levels ≥100 mg/dL as the reference, the baseline LDL-C level <70 mg/dL was independently associated with an increased incidence of cardiovascular death (adjusted hazard ratio, 1.68 [95% CI, 1.30-2.17]) and 3-point major adverse cardiovascular event (adjusted hazard ratio, 1.37 [95% CI, 1.10-1.71]). Conclusions In this Korean acute myocardial infarction registry, the baseline LDL-C level <70 mg/dL was significantly associated with an increased incidence of long-term cardiovascular events after discharge. (COREA [Cardiovascular Risk and Identification of Potential High-Risk Population]-Acute Myocardial Infarction Registry; NCT02806102). Registration URL: https://www.clinicaltrials.gov/; Unique identifier: NCT02806102.


Assuntos
Inibidores de Hidroximetilglutaril-CoA Redutases , Infarto do Miocárdio , Acidente Vascular Cerebral , Assistência ao Convalescente , Idoso , LDL-Colesterol , Feminino , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/efeitos adversos , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/induzido quimicamente , Infarto do Miocárdio/tratamento farmacológico , Alta do Paciente , Acidente Vascular Cerebral/induzido quimicamente , Acidente Vascular Cerebral/epidemiologia , Resultado do Tratamento
3.
PLoS One ; 17(8): e0266118, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36006991

RESUMO

BACKGROUND: Immunization stress-related responses presenting as stroke-like symptoms could develop following COVID-19 vaccination. Therefore, this study aimed to describe the clinical characteristics of immunization stress-related responses causing stroke-like events following COVID-19 vaccination in Thailand. METHODS: We conducted a retrospective study of the secondary data of reported adverse events after COVID-19 immunization that presented with neurologic manifestations. Between March 1 and July 31, 2021, we collected and analyzed the medical records of 221 patients diagnosed with stroke-like symptoms following immunization. Two majority types of vaccines were used at the beginning of the vaccination campaign, including CoronaVac (Sinovac) or ChAdOx1 (AstraZeneca). Demographic and medical data included sex, age, vaccine type, sequence dose, time to event, laboratory data, and recovery status as defined by the modified Rankin score. The affected side was evaluated for associations with the injection site. RESULTS: Overall, 221 patients were diagnosed with immunization stress-related responses (stroke-like symptoms) following CoronaVac (Sinovac) or ChAdOx1 (AstraZeneca) vaccinations. Most patients (83.7%) were women. The median (interquartile range) age of onset was 34 (28-42) years in patients receiving CoronaVac and 46 (33.5-60) years in those receiving ChAdOx1. The median interval between vaccination and symptom onset for each vaccine type was 60 (16-960) min and 30 (8.8-750) min, respectively. Sensory symptoms were the most common symptomology. Most patients (68.9%) developed symptoms on the left side of the body; 99.5% of the patients receiving CoronaVac and 100% of those receiving ChAdOx1 had a good outcome (modified Rankin scores ≤2, indicating slight or no disability). CONCLUSIONS: Immunization stress-related responses presenting as stroke-like symptoms can develop after COVID-19 vaccination. Symptoms more likely to occur on the injection side are transient (i.e., without permanent pathological deficits). Public education and preparedness are important for administering successful COVID-19 vaccination programs.


Assuntos
Vacinas contra COVID-19 , COVID-19 , Acidente Vascular Cerebral , Adulto , COVID-19/prevenção & controle , Vacinas contra COVID-19/efeitos adversos , ChAdOx1 nCoV-19 , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Acidente Vascular Cerebral/induzido quimicamente , Tailândia , Vacinação/efeitos adversos
4.
Prostate ; 82(15): 1477-1480, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-35915869

RESUMO

BACKGROUND: Although androgen deprivation therapy has known cardiovascular risks, it is unclear if its duration is related to cardiovascular risks. This study thus aimed to investigate the associations between gonadotrophin-releasing hormone (GnRH) agonist use duration and cardiovascular risks. METHODS: This retrospective cohort study included adult patients with prostate cancer receiving GnRH agonists in Hong Kong during 1999-2021. Patients who switched to GnRH antagonists, underwent bilateral orchidectomy, had <6 months of GnRH agonist, prior myocardial infarction (MI), or prior stroke was excluded. All patients were followed up until September 2021 for a composite endpoint of MI and stroke. Multivariable competing-risk regression using the Fine-Gray subdistribution model was used, with mortality from any cause as the competing event. RESULTS: In total, 4038 patients were analyzed (median age 74.9 years old, interquartile range (IQR) 68.7-80.8 years old). Over a median follow-up of 4.1 years (IQR 2.1-7.5 years), longer GnRH agonists use was associated with higher risk of the endpoint (sub-hazard ratio per year 1.04 [1.01-1.06], p = 0.001), with those using GnRH agonists for ≥2 years having an estimated 23% increase in the sub-hazard of the endpoint (sub-hazard ratio 1.23 [1.04-1.46], p = 0.017). CONCLUSION: Longer GnRH agonist use may be associated with greater cardiovascular risks.


Assuntos
Neoplasias da Próstata , Acidente Vascular Cerebral , Adulto , Idoso , Idoso de 80 Anos ou mais , Antagonistas de Androgênios , Androgênios , Hormônio Liberador de Gonadotropina , Humanos , Masculino , Estudos Retrospectivos , Medição de Risco , Acidente Vascular Cerebral/induzido quimicamente , Acidente Vascular Cerebral/epidemiologia
5.
Mayo Clin Proc ; 97(8): 1483-1492, 2022 08.
Artigo em Inglês | MEDLINE | ID: mdl-35933134

RESUMO

OBJECTIVE: To evaluate the risks of recurrent stroke and major bleeding events with clopidogrel and aspirin use among patients aged 80 years or older. PATIENTS AND METHODS: This retrospective cohort study was conducted using the Full Population Data of the Health and Welfare Database in Taiwan. Patients aged 80 years or older who received monotherapy with clopidogrel or aspirin following hospitalization for primary acute ischemic stroke between January 1, 2009, and December 31, 2018, were included. Inverse probability of treatment weighting was used to balance measured covariates between clopidogrel and aspirin users. Measured outcomes included recurrent acute ischemic stroke, acute myocardial infarction, composite cardiovascular events (recurrent stroke or acute myocardial infarction), intracranial hemorrhage, major gastrointestinal tract bleeding, and composite major bleeding events (intracranial hemorrhage or major gastrointestinal tract bleeding). RESULTS: A total of 15,045 patients were included in the study, 1979 of whom used clopidogrel and 13,066 who used aspirin following hospitalization for primary acute ischemic stroke. Clopidogrel use was associated with significantly lower risk of recurrent acute ischemic stroke (hazard ratio [HR], 0.89; 95% CI, 0.83 to 0.96; P=.002), composite cardiovascular events (HR, 0.88; 95% CI, 0.82 to 0.95; P<.001), intracranial hemorrhage (HR, 0.71; 95% CI, 0.56 to 0.90; P=.005), and composite major bleeding events (HR, 0.89; 95% CI, 0.80 to 0.99; P=.04) compared with aspirin use. CONCLUSION: In patients aged 80 years or older with primary acute ischemic stroke, clopidogrel users had lower risks of recurrent stroke and the composite cardiovascular events compared with aspirin users. Clopidogrel users also had lower risks of intracranial hemorrhage and the composite major bleeding events compared with aspirin users.


Assuntos
AVC Isquêmico , Infarto do Miocárdio , Acidente Vascular Cerebral , Idoso , Aspirina/efeitos adversos , Infarto Cerebral , Clopidogrel/efeitos adversos , Quimioterapia Combinada , Hemorragia Gastrointestinal/induzido quimicamente , Hemorragia Gastrointestinal/epidemiologia , Humanos , Hemorragias Intracranianas/induzido quimicamente , Hemorragias Intracranianas/epidemiologia , Infarto do Miocárdio/induzido quimicamente , Inibidores da Agregação Plaquetária/efeitos adversos , Estudos Retrospectivos , Prevenção Secundária , Acidente Vascular Cerebral/induzido quimicamente , Resultado do Tratamento
6.
J Neurol ; 269(10): 5262-5271, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-35776193

RESUMO

BACKGROUND: At present, studies regarding the efficacy and safety of tenecteplase for the treatment of patients with acute ischemic stroke (AIS) are still limited and inconsistent. The purpose of this systematic review and meta-analysis is to compare the efficacy and safety of tenecteplase with alteplase for the treatment of AIS patients. METHODS: Literature search was conducted in PubMed, Embase, and Cochrane Library up to May 10, 2022. Primary outcomes of this study included 90-day good outcome (defined as an mRS score of 0-2) and 90-day excellent outcome (defined as an mRS score of 0-1). Risk ratios (RRs) with 95% confidence intervals (95% CIs) were calculated using a random-effect model for each outcome. RESULTS: Fourteen studies with a total of 3537 patients were finally included in this meta-analysis. There was no statistical difference between patients receiving tenecteplase and those receiving alteplase in the rates of 90-day good outcome (RR 1.01; 95% CI 0.91-1.13; P = 0.79) and 90-day excellent outcome (RR 1.04; 95% CI 0.92-1.19; P = 0.50). Patients receiving tenecteplase might associated with higher incidence of early neurologic improvement compared with those receiving alteplase (RR 1.29; 95% CI 1.04-1.61; P = 0.02). In addition, no statistical difference was observed between the two groups in other outcomes. CONCLUSION: This meta-analysis indicated that tenecteplase in AIS patients is as safe and effective as alteplase and might provide more benefit than alteplase. However, due to several inherent limitations of this study, more prospective studies should be conducted to confirm the above results.


Assuntos
Isquemia Encefálica , AVC Isquêmico , Acidente Vascular Cerebral , Isquemia Encefálica/tratamento farmacológico , Fibrinolíticos/uso terapêutico , Humanos , AVC Isquêmico/tratamento farmacológico , Estudos Prospectivos , Acidente Vascular Cerebral/induzido quimicamente , Acidente Vascular Cerebral/tratamento farmacológico , Tenecteplase/uso terapêutico , Ativador de Plasminogênio Tecidual/efeitos adversos , Resultado do Tratamento
7.
Methods Mol Biol ; 2515: 75-87, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35776346

RESUMO

The endothelin-1 (ET-1) model of stroke involves the stereotactic injection of the vasoconstrictor ET-1 to produce a focal ischemic injury. In rats, this model produces consistent deficits, in contrast to more variable results in mice. In this chapter, we describe a new method to induce a murine focal ischemic cortical stroke by injecting L-NAME, another potent vasoconstrictor , in combination with ET-1 into the sensorimotor cortex. This ET-1 /L-NAME stroke induction protocol produces consistent focal cortical infarcts and sensorimotor functional impairments in C57BL/6 mice.


Assuntos
Endotelina-1 , Acidente Vascular Cerebral , Animais , Modelos Animais de Doenças , Camundongos , Camundongos Endogâmicos C57BL , NG-Nitroarginina Metil Éster/farmacologia , Ratos , Acidente Vascular Cerebral/induzido quimicamente , Vasoconstritores
8.
J Stroke Cerebrovasc Dis ; 31(9): 106612, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-35863261

RESUMO

BACKGROUND AND PURPOSE: Direct oral anticoagulant (DOAC) ingestion within 48 h is an exclusion for thrombolysis in acute ischemic stroke (AIS) patients. We aim to shed light on pharmacokinetic correlates and outcomes in patients with AIS excluded from thrombolysis due to DOAC use. METHODS: This is a single center retrospective study of consecutive patients with AIS within 4.5 h from last known normal and excluded from thrombolytic therapy due to confirmed Xa inhibitor DOAC (DOACXa) intake within the prior 48 h. We used linear regression to test the correlation between time from last DOACXa ingestion and anti-Xa level. RESULTS: Over a period of 2.5 years, we identified 44 patients who did not receive thrombolysis because of presumed DOAC intake within 48 h. In adjusted linear regression, there was an association between time from last DOAC ingestion and Xa level (beta = -0.69, p < 0.001). Among the 37 patients with known atrial fibrillation not receiving alteplase due to DOAC use, the 90-day mortality was 35.1% (13/37) and 77% (10/13) of deaths were stroke related. CONCLUSIONS: Patients with AIS on DOAC therapy face a heightened risk of mortality. Studies are needed to investigate the safety and efficacy of thrombolysis in such patients based on time of last DOAC ingestion and/or anti-Xa/drug level.


Assuntos
Fibrilação Atrial , AVC Isquêmico , Acidente Vascular Cerebral , Administração Oral , Anticoagulantes/uso terapêutico , Fibrilação Atrial/diagnóstico , Fibrilação Atrial/tratamento farmacológico , Inibidores do Fator Xa/efeitos adversos , Heparina de Baixo Peso Molecular/uso terapêutico , Humanos , Estudos Retrospectivos , Acidente Vascular Cerebral/induzido quimicamente , Acidente Vascular Cerebral/diagnóstico , Acidente Vascular Cerebral/tratamento farmacológico
9.
J Am Heart Assoc ; 11(11): e023545, 2022 Jun 07.
Artigo em Inglês | MEDLINE | ID: mdl-35656979

RESUMO

Background We sought to determine recurrent stroke predictors among patients with embolic strokes of undetermined source (ESUS). Methods and Results We applied Cox proportional hazards models to identify clinical features associated with recurrent stroke among participants enrolled in RE-SPECT ESUS (Randomized, Double-Blind, Evaluation in Secondary Stroke Prevention Comparing the Efficacy and Safety of the Oral Thrombin Inhibitor Dabigatran Etexilate Versus Acetylsalicylic Acid in Patients With Embolic Stroke of Undetermined Source) trial, an international clinical trial evaluating dabigatran versus aspirin for patients with ESUS. During a median follow-up of 19 months, 384 of 5390 participants had recurrent stroke (annual rate, 4.5%). Multivariable models revealed that stroke or transient ischemic attack before the index event (hazard ratio [HR], 2.27 [95% CI, 1.83-2.82]), creatinine clearance <50 mL/min (HR, 1.69 [95% CI, 1.23-2.32]), male sex (HR, 1.60 [95% CI, 1.27-2.02]), and CHA2DS2-VASc ≥4 (HR, 1.55 [95% CI, 1.15-2.08] and HR, 1.66 [95% CI, 1.21-2.26] for scores of 4 and ≥5, respectively) versus CHA2DS2-VASc of 2 to 3, were independent predictors for recurrent stroke. Conclusions In RE-SPECT ESUS trial, expected risk factors previously linked to other common stroke causes were associated with stroke recurrence. These data help define high-risk groups for subsequent stroke that may be useful for clinicians and for researchers designing trials among patients with ESUS. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT02239120.


Assuntos
AVC Embólico , Embolia Intracraniana , Acidente Vascular Cerebral , Aspirina/uso terapêutico , Infarto Cerebral , Dabigatrana/uso terapêutico , Humanos , Embolia Intracraniana/diagnóstico por imagem , Embolia Intracraniana/etiologia , Masculino , Fatores de Risco , Acidente Vascular Cerebral/induzido quimicamente , Acidente Vascular Cerebral/prevenção & controle , Tomografia Computadorizada de Emissão de Fóton Único
10.
Neuroepidemiology ; 56(4): 240-249, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35753307

RESUMO

INTRODUCTION: Statins are effective in preventing vascular disease and are widely recommended and used for the secondary prevention of ischemic stroke. However, there is concern from trials that statins might increase the risk of hemorrhagic stroke, partially reducing their benefit. We sought to systematically review the latest evidence on this question. METHODS: Four electronic databases were searched to identify published randomized controlled trials (RCTs) and observational cohort studies (search date December 2020). Two independent reviewers carried out the eligibility assessment based on predefined inclusion criteria. We examined the outcomes of recurrent stroke (after ischemic stroke) of any type, and separately recurrent ischemic stroke and recurrent hemorrhagic stroke. RCTs and observational cohort studies were meta-analyzed separately. Odds ratios (ORs) were used to assess the effect of statin therapy. Meta-analysis was conducted using RevMan 5.4 software. RESULTS: We retrieved 559 papers in searches, of which 11 RCTs and 12 observational cohort studies were included. Both RCTs and observational studies found that statins reduced the odds of stroke of any type in those with an initial ischemic stroke (11 RCTs: OR = 0.87, 95% CI [0.77,0.97]; p = 0.02; 12 cohort studies: OR = 0.80, 95% CI [0.66, 0.96]; p = 0.02). Both RCTs and observational studies found that recurrence of ischemic stroke was reduced by statins (6 RCTs: OR = 0.81, 95% CI [0.70, 0.93]; p = 0.002; 3 observational studies: OR = 0.67, 95% CI [0.61, 0.75]; p < 0.00001). Data from 7 RCTs and 8 cohort studies did not find a significant difference in hemorrhagic stroke but could not rule out a substantial increase or reduction (7 RCTs: OR = 1.15, 95% CI [0.62, 2.13]; p = 0.66; 8 cohort studies: OR = 0.93, 95% CI [0.71, 1.21]; p = 0.59). CONCLUSIONS: In people who have experienced an ischemic stroke, statins reduce the risk of recurrent stroke of any type medicated through a reduction of ischemic stroke. We found no increase in the risk of hemorrhagic stroke.


Assuntos
Acidente Vascular Cerebral Hemorrágico , Inibidores de Hidroximetilglutaril-CoA Redutases , AVC Isquêmico , Acidente Vascular Cerebral , Infarto Cerebral , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Estudos Observacionais como Assunto , Ensaios Clínicos Controlados Aleatórios como Assunto , Acidente Vascular Cerebral/induzido quimicamente , Acidente Vascular Cerebral/tratamento farmacológico , Acidente Vascular Cerebral/prevenção & controle
11.
Vaccine ; 40(32): 4394-4402, 2022 07 30.
Artigo em Inglês | MEDLINE | ID: mdl-35667917

RESUMO

BACKGROUND: Rapid deployment of COVID-19 vaccines is challenging for safety surveillance, especially on adverse events of special interest (AESIs) that were not identified during the pre-licensure studies. This study evaluated the risk of hospitalisations for predefined diagnoses among the vaccinated population in Malaysia. METHODS: Hospital admissions for selected diagnoses between 1 February 2021 and 30 September 2021 were linked to the national COVID-19 immunisation register. We conducted self-controlled case-series study by identifying individuals who received COVID-19 vaccine and diagnosis of thrombocytopenia, venous thromboembolism, myocardial infarction, myocarditis/pericarditis, arrhythmia, stroke, Bell's Palsy, and convulsion/seizure. The incidence of events was assessed in risk period of 21 days postvaccination relative to the control period. We used conditional Poisson regression to calculate the incidence rate ratio (IRR) and 95% confidence interval (CI) with adjustment for calendar period. RESULTS: There was no increase in the risk for myocarditis/pericarditis, Bell's Palsy, stroke, and myocardial infarction in the 21 days following either dose of BNT162b2, CoronaVac, and ChAdOx1 vaccines. A small increased risk of venous thromboembolism (IRR 1.24; 95% CI 1.02, 1.49), arrhythmia (IRR 1.16, 95% CI 1.07, 1.26), and convulsion/seizure (IRR 1.26; 95% CI 1.07, 1.48) was observed among BNT162b2 recipients. No association between CoronaVac vaccine was found with all events except arrhythmia (IRR 1.15; 95% CI 1.01, 1.30). ChAdOx1 vaccine was associated with an increased risk of thrombocytopenia (IRR 2.67; 95% CI 1.21, 5.89) and venous thromboembolism (IRR 2.22; 95% CI 1.17, 4.21). CONCLUSION: This study shows acceptable safety profiles of COVID-19 vaccines among recipients of BNT162b2, CoronaVac, and ChAdOx1 vaccines. This information can be used together with effectiveness data for risk-benefit analysis of the vaccination program. Further surveillance with more data is required to assess AESIs following COVID-19 vaccination in short- and long-term.


Assuntos
Vacinas contra COVID-19 , COVID-19 , Vacina BNT162 , Paralisia de Bell/induzido quimicamente , Paralisia de Bell/epidemiologia , COVID-19/epidemiologia , COVID-19/prevenção & controle , Vacinas contra COVID-19/efeitos adversos , ChAdOx1 nCoV-19 , Humanos , Malásia/epidemiologia , Infarto do Miocárdio/induzido quimicamente , Infarto do Miocárdio/epidemiologia , Miocardite/induzido quimicamente , Miocardite/epidemiologia , Pericardite/induzido quimicamente , Pericardite/epidemiologia , Convulsões/induzido quimicamente , Acidente Vascular Cerebral/induzido quimicamente , Acidente Vascular Cerebral/epidemiologia , Trombocitopenia/induzido quimicamente , Trombocitopenia/epidemiologia , Vacinas de Produtos Inativados , Tromboembolia Venosa/induzido quimicamente , Tromboembolia Venosa/epidemiologia
12.
Sci Total Environ ; 840: 156626, 2022 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-35697224

RESUMO

Most studies have explored the adverse health effects of polycyclic aromatic hydrocarbons (PAH) occupational exposure. However, the general population is also exposed to PAH, mainly through the diet. The goal of the present study is thus to investigate the association between PAH dietary exposure and mortality risk in middle-aged women of the E3N (Étude Épidémiologique auprès de femmes de la mutuelle générale de l'Éducation Nationale) French prospective cohort. The study included 72,513 women, whom completed a validated semi-quantitative food frequency questionnaire on 208 food items in 1993. Food contamination levels were assessed using data provided by the Anses (French Agency for Food, Environmental and Occupational Health & Safety) in the framework of the French second total diet study. PAH dietary exposure was studied as the sum of four PAH (PAH4), namely benzo[a]pyrene (BaP), chrysene (CHR), benzo[a]anthracene (BaA) and benzo[b]fluoranthene (BbF). Cox proportional hazard models were used to estimate hazard ratios (HR) and their 95 % confidence intervals (CI) for the risk of all-cause mortality as well as all-cancer, specific cancer (separately from breast, lung/tracheal, and colorectal cancer), cardiovascular disease (CVD), and specific CVD (including only stroke and coronary heart disease) mortality. During follow-up (1993-2011), 4620 validated deaths were reported, of which 2726 due to cancer and 584 to CVD. The median PAH4 dietary intake was 66.1 ng/day. There was no significant association between PAH4 dietary intake and the risk of all-cause, all-cancer, breast cancer, colorectal cancer, all-CVD and stroke and coronary heart disease mortality. On the contrary, we observed a positive and statistically significant association between PAH4 dietary intake and lung/tracheal cancer mortality risk, with a stronger association among current smokers than among former smokers and never smokers. In this study, we observed an association between PAH dietary exposure and lung/tracheal cancer mortality risk, especially among current smokers.


Assuntos
Doenças Cardiovasculares , Neoplasias , Hidrocarbonetos Policíclicos Aromáticos , Acidente Vascular Cerebral , Doenças Cardiovasculares/induzido quimicamente , Exposição Dietética , Feminino , Humanos , Pessoa de Meia-Idade , Neoplasias/induzido quimicamente , Neoplasias/epidemiologia , Hidrocarbonetos Policíclicos Aromáticos/análise , Estudos Prospectivos , Acidente Vascular Cerebral/induzido quimicamente
13.
Lancet Planet Health ; 6(6): e496-e503, 2022 06.
Artigo em Inglês | MEDLINE | ID: mdl-35709807

RESUMO

BACKGROUND: The evidence for a causal relationship between long-term ozone exposure and cardiovascular mortality is inconclusive, and most published data are from high-income countries. We aimed to investigate the association between long-term exposure to ozone and cardiovascular mortality in China, the most populous middle-income country. METHODS: We did a nationwide cohort study comprising Chinese adults aged 18 years and older from the 2010-11 China Chronic Disease and Risk Factors Surveillance project; participants were followed up until Dec 31, 2018, or the date of death. Data on participants' deaths were obtained through linkage to the Disease Surveillance Point system, a national death registration database. Residential ozone exposure was estimated with a previously developed random forest model. We applied stratified Cox proportional hazards models to estimate the associations of ozone with mortality due to overall cardiovascular diseases, ischaemic heart disease, and stroke. The models were stratified by age and sex and adjusted for a set of individual-level and regional covariates. Warm-season average ozone concentration for the previous 1-3 years was added as a time-varying variable. We also did subgroup analyses by age, sex, level of education, smoking status, urban or rural residence, and geographical region. FINDINGS: Data were analysed for 96 955 participants. The warm-season average ozone concentration during the follow-up period was 89·7 µg/m3 (SD 14·4). In the fully adjusted models, we observed significant and positive associations between ozone and mortality from overall cardiovascular diseases (hazard ratio [HR] 1·093 [95% CI 1·046-1·142] per 10 µg/m3 increase in warm-season ozone concentrations), ischaemic heart disease (1·184 [1·099-1·276] per 10 µg/m3 increase in warm-season ozone concentrations), and stroke (1·063 [1·002- 1·128] per 10 µg/m3 increase in warm-season ozone concentrations). After adjusting for fine particulate matter, the associations with overall cardiovascular disease and ischaemic heart disease mortality were almost unchanged, whereas the association with stroke mortality lost statistical significance. The association of long-term ozone exposure with cardiovascular mortality was more prominent in people aged 65 years and older than in those younger than 65 years. We did not find any effect modification of sex, level of education, smoking status, urban or rural residence, and geographical region. We observed an almost linear exposure-response relationship between ozone and cardiovascular mortality. INTERPRETATION: This study is, to the best of our knowledge, the first nationwide cohort study to show that long-term ozone exposure contributes to elevated risks of cardiovascular mortality, particularly from ischaemic heart disease, in a middle-income setting. The exposure-response function generated from this study could potentially inform future air quality standard revisions and environmental health impact assessments. FUNDING: National Natural Science Foundation of China.


Assuntos
Doenças Cardiovasculares , Isquemia Miocárdica , Ozônio , Acidente Vascular Cerebral , Adulto , China/epidemiologia , Estudos de Coortes , Humanos , Isquemia Miocárdica/induzido quimicamente , Ozônio/efeitos adversos , Ozônio/análise , Acidente Vascular Cerebral/induzido quimicamente
14.
Acta Med Acad ; 51(1): 29-34, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35695400

RESUMO

OBJECTIVE: Clopidogrel is a common antiplatelet used as secondary prevention of ischemic stroke, known to have better efficacy than aspirin, with a equivalent safety profile. However, clopidogrel resistance is not uncommon but has not been widely studied in Asia. This study will further assess clopidogrel resistance and its risk factors. MATERIALS AND METHODS: A cross-sectional study was conducted at Rumah Sakit Universitas, Indonesia, and Rumah Sakit Cipto Mangunkusumo, Indonesia in 2020-2021. All patients had had at least one episode of ischemic stroke. Clopidogrel resistance was assessed using a VerifyNow assay. RESULTS: 57 subjects were enrolled in this study. We found 15.8% of subjects were clopidogrel resistant. Gender was significantly associated with clopidogrel resistance, with males having 80% lower clopidogrel resistance (OR 0.2 (95% CI 0.022 - 0.638); P=0.006). Meanwhile, smoking was not associated with clopidogrel responsiveness (P=0.051). We found no association between haemoglobin, blood glucose, HbA1c, cholesterol, liver enzymes, serum urea concentration or creatinine levels and clopidogrel resistance. CONCLUSION: Clopidogrel remains an effective treatment to prevent recurrent ischemic stroke in Indonesia. Further studies are needed to assess gene polymorphism and clopidogrel resistance, which may explain the findings of this study.


Assuntos
AVC Isquêmico , Acidente Vascular Cerebral , Clopidogrel/uso terapêutico , Estudos Transversais , Quimioterapia Combinada , Humanos , Indonésia , Masculino , Inibidores da Agregação Plaquetária/uso terapêutico , Fatores de Risco , Acidente Vascular Cerebral/induzido quimicamente , Acidente Vascular Cerebral/tratamento farmacológico , Acidente Vascular Cerebral/prevenção & controle , Ticlopidina/efeitos adversos , Resultado do Tratamento
15.
Artigo em Inglês | MEDLINE | ID: mdl-35682266

RESUMO

Previous studies found that exposure to ambient nitrogen dioxide (NO2) was associated with an increased risk of incident stroke, but few studies have been conducted for relatively low NO2 pollution areas. In this study, the short-term effects of NO2 on the risk of incident stroke in a relatively low-pollution area, Enshi city of Hubei Province, China, were investigated through time-series analysis. Daily air-pollution data, meteorological data, and stroke incidence data of residents in Enshi city from 1 January 2015 to 31 December 2018 were collected. A time-series analysis using a generalised additive model (GAM) based on Poisson distribution was applied to explore the short-term effects of low-level NO2 exposure on the risk of incident stroke and stroke subtypes, as well as possible age, sex, and seasonal differences behind the effects. In the GAM model, potential confounding factors, such as public holidays, day of the week, long-term trends, and meteorological factors (temperature and relative humidity), were controlled. A total of 9122 stroke incident cases were included during the study period. We found that NO2 had statistically significant effects on the incidence of stroke and ischemic stroke, estimated by excess risk (ER) of 0.37% (95% CI: 0.04-0.70%) and 0.58% (95% CI: 0.18-0.98%), respectively. For the cumulative lag effects, the NO2 still had a statistically significant effect on incident ischemic stroke, estimated by ER of 0.61% (95% CI: 0.01-1.21%). The two-pollutant model showed that the effects of NO2 on incident total stroke were still statistically significant after adjusting for other air pollutants (PM2.5, PM10, SO2, CO, and O3). In addition, the effects of NO2 exposure on incident stroke were statistically significant in elderly (ER = 0.75%; 95% CI: 0.11-1.40%), males (ER = 0.47%; 95% CI: 0.05-0.89%) and cold season (ER = 0.83%; 95% CI: 0.15-1.51%) subgroups. Our study showed that, as commonly observed in high-pollution areas, short-term exposure to low-level NO2 was associated with an increased risk of incident stroke, including ischemic stroke. Males and elderly people were more vulnerable to the effects of NO2, and the adverse effects might be promoted in the cold season.


Assuntos
Poluentes Atmosféricos , Poluição do Ar , AVC Isquêmico , Acidente Vascular Cerebral , Idoso , Poluentes Atmosféricos/análise , Poluição do Ar/efeitos adversos , Poluição do Ar/análise , China/epidemiologia , Humanos , Masculino , Dióxido de Nitrogênio/análise , Material Particulado/análise , Acidente Vascular Cerebral/induzido quimicamente , Acidente Vascular Cerebral/epidemiologia
16.
Eur J Neurol ; 29(9): 2864-2868, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-35652757

RESUMO

BACKGROUND AND PURPOSE: The purpose was to determine whether prior use of antiplatelet therapy modifies the effect of dual antiplatelet therapy in patients with acute minor ischaemic stroke or transient ischaemic attack. METHODS: A systematic review and meta-analysis of randomized controlled trials was performed comparing dual antiplatelet therapy to aspirin that reported subgroup analysis by prior antiplatelet use, adhering to the Cochrane Collaboration Guidelines. A fixed-effects meta-analysis was used to estimate a pooled treatment effect overall in subgroups with prior aspirin therapy and without prior aspirin therapy. Difference in treatment effect was assessed by testing p for interaction. The primary outcome measure was recurrent vascular events. RESULTS: Three eligible randomized controlled trials were identified, including 4831 participants with pre-existing antiplatelet use and 16,236 participants without pre-existing aspirin use. Recurrent vascular events occurred in 7.2% (95% confidence interval [CI] 4.3-10) of those without pre-existing aspirin use versus 7.3% (95% CI 4.1-10) of those receiving prior aspirin therapy. Effect of dual antiplatelet therapy on the primary outcome measure was consistent in participants with no prior aspirin use (odds ratio 0.75, 95% CI 0.66-0.84) compared to those taking aspirin before randomization (odds ratio 0.79, 95% CI 0.63-0.998) (p interaction = 0.66). The number needed to treat in the aspirin-naïve group was 55 (95% CI 37-107) compared to 66 (95% CI 32 to -746) in those on prior aspirin therapy. CONCLUSIONS: It was found that the effectiveness of dual antiplatelet therapy in patients with minor ischaemic stroke or high risk transient ischaemic attack does not significantly differ in patients with prior aspirin exposure; therefore there should be no influence on the decision to use dual antiplatelet therapy.


Assuntos
Isquemia Encefálica , Ataque Isquêmico Transitório , AVC Isquêmico , Acidente Vascular Cerebral , Aspirina/uso terapêutico , Isquemia Encefálica/induzido quimicamente , Isquemia Encefálica/complicações , Isquemia Encefálica/tratamento farmacológico , Quimioterapia Combinada , Humanos , Ataque Isquêmico Transitório/tratamento farmacológico , Inibidores da Agregação Plaquetária , Acidente Vascular Cerebral/induzido quimicamente , Acidente Vascular Cerebral/tratamento farmacológico
17.
Cardiovasc Diabetol ; 21(1): 92, 2022 06 03.
Artigo em Inglês | MEDLINE | ID: mdl-35658864

RESUMO

BACKGROUND: Sodium-glucose cotransporter-2 inhibitors (SGLT2i) have proven cardiovascular benefits in patients with type 2 diabetes (T2D). This self-controlled case series study aims to evaluate whether metformin use and SGLT2i-associated erythrocytosis influence its cardiovascular benefits. METHODS: T2D patients with metformin and/or SGLT2i prescriptions between 2015 and 2020 were identified from the Hong Kong population. Study outcomes were composite cardiovascular diseases (CVD), coronary heart disease (CHD), hospitalisation for heart failure (HHF), stroke, and erythrocytosis. Risk periods were patient-time divided into four mutually exclusive windows: (i) 'baseline period' of metformin use without SGLT2i; (ii) pre-SGLT2i period; (iii) exposure to SGLT2i without metformin; and (iv) exposure to the drug combination. Another SCCS model was applied to evaluate the association between erythrocytosis and cardiovascular outcomes regarding SGLT2i exposure. Four mutually exclusive risk periods included (i) SGLT2i exposure with erythrocytosis; (ii) SGLT2i exposure without erythrocytosis; (iii) absence of SGLT2i exposure with erythrocytosis; and (iv) absence of SGLT2i exposure without erythrocytosis. Incidence rate ratios (IRR) of events at different risk periods were estimated using conditional Poisson regression model. RESULTS: Among 20,861 patients with metformin and/or SGLT2i prescriptions, 2575 and 1700 patients with events of composite CVD and erythrocytosis were identified, respectively. Compared to metformin use without SGLT2i, SGLT2i initiation was associated with lower risks of composite CVD, CHD, and HHF-regardless of the presence (CVD: IRR = 0.43, 95% CI 0.37-0.51; CHD: IRR = 0.44, 95% CI 0.37-0.53; HHF: IRR = 0.29, 95% CI 0.22-0.40; all p < 0.001) and absence of concomitant metformin (CVD: IRR = 0.31, 95% CI 0.20-0.48; CHD: IRR = 0.38, 95% CI 0.25-0.59; HHF: IRR = 0.17, 95% CI 0.09-0.31; all p < 0.001); while SGLT2i was neutral on stroke risk. Compared to metformin-SGLT2i combination, exposure to SGLT2i alone was associated with comparable risks of all cardiovascular outcomes (all p > 0.05). Incidence rates of erythrocytosis at baseline, SGLT2i without and with metformin use periods were 0.75, 3.06 and 3.27 per 100 person-years, respectively. SGLT2i users who developed erythrocytosis had lower risk of HHF (IRR = 0.38, 95% CI 0.14-0.99, p = 0.049) than those who did not. CONCLUSIONS: Our real-world data suggested that SGLT2i-associated cardiovascular benefits were not attenuated by metformin use. Further studies will delineate the role of erythrocytosis as a surrogate marker of SGLT2i-associated cardiovascular benefit in reducing HHF.


Assuntos
Doenças Cardiovasculares , Diabetes Mellitus Tipo 2 , Insuficiência Cardíaca , Metformina , Policitemia , Inibidores do Transportador 2 de Sódio-Glicose , Acidente Vascular Cerebral , Doenças Cardiovasculares/diagnóstico , Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/prevenção & controle , Diabetes Mellitus Tipo 2/diagnóstico , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/epidemiologia , Insuficiência Cardíaca/epidemiologia , Humanos , Metformina/efeitos adversos , Policitemia/induzido quimicamente , Policitemia/diagnóstico , Policitemia/epidemiologia , Inibidores do Transportador 2 de Sódio-Glicose/efeitos adversos , Acidente Vascular Cerebral/induzido quimicamente
18.
Front Public Health ; 10: 883383, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35669761

RESUMO

Objective: Living alone is often associated with reduced social support. However, there are limited data on the relationship between living alone and cardiovascular events or hypoglycemia in patients with type 2 diabetes mellitus (T2DM). This study reports a post-hoc analysis of the "Action to Control Cardiovascular Risk in Diabetes (ACCORD)" study. Research Design and Methods: The Cox proportional hazard models were used to compare the hazard ratios (HRs) for the adverse health events selected as primary endpoints in the study participants; these were compared between those living alone and those living with others. The primary outcomes were hypoglycemia requiring any assistance (HAA), hypoglycemia requiring medical assistance (HMA), and major cardiovascular events (MACEs, including cardiac death, non-fatal myocardial infarction (MI), and non-fatal stroke). Our study included 10,249 participants (2,078 living alone) with a follow-up period of 4.91 ± 1.22 years. Results: After a multivariable adjustment, the risk of HAA, HMA, and MACEs did not differ significantly between participants living alone and those living with others (HAA, HR: 0.88, 95% CI: 0.75-1.04, P = 0.13; HMA, HR: 1.11, 95% CI: 0.92-1.34, P = 0.26; MACEs, HR: 0.98, 95% CI: 0.80-1.19, P = 0.82). Participants living alone had higher levels of glycated hemoglobin in the middle follow-up period than those living with others. Conclusions: In patients with T2DM, living alone did not increase the risk of cardiovascular events (cardiac death, non-fatal MI, or non-fatal stroke) and hypoglycemia. Patients living alone had higher Hb1AC levels than those living with others. Clinicians should consider an effective blood glucose control regardless of their living arrangement.


Assuntos
Diabetes Mellitus Tipo 2 , Hipoglicemia , Acidente Vascular Cerebral , Morte , Diabetes Mellitus Tipo 2/complicações , Ambiente Domiciliar , Humanos , Hipoglicemia/induzido quimicamente , Hipoglicemia/complicações , Hipoglicemiantes/uso terapêutico , Acidente Vascular Cerebral/induzido quimicamente , Acidente Vascular Cerebral/complicações
19.
BMJ ; 377: e069116, 2022 05 04.
Artigo em Inglês | MEDLINE | ID: mdl-35508321

RESUMO

OBJECTIVE: To compare the impact of ezetimibe and proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors on cardiovascular outcomes in adults taking maximally tolerated statin therapy or who are statin intolerant. DESIGN: Network meta-analysis. DATA SOURCES: Medline, EMBASE, and Cochrane Library up to 31 December 2020. ELIGIBILITY CRITERIA FOR SELECTING STUDIES: Randomised controlled trials of ezetimibe and PCSK9 inhibitors with ≥500 patients and follow-up of ≥6 months. MAIN OUTCOME MEASURES: We performed frequentist fixed-effects network meta-analysis and GRADE (grading of recommendations, assessment, development, and evaluation) to assess certainty of evidence. Results included relative risks (RR) and absolute risks per 1000 patients treated for five years for non-fatal myocardial infarction (MI), non-fatal stroke, all-cause mortality, and cardiovascular mortality. We estimated absolute risk differences assuming constant RR (estimated from network meta-analysis) across different baseline therapies and cardiovascular risk thresholds; the PREDICT risk calculator estimated cardiovascular risk in primary and secondary prevention. Patients were categorised at low to very high cardiovascular risk. A guideline panel and systematic review authors established the minimal important differences (MID) of 12 per 1000 for MI and 10 per 1000 for stroke. RESULTS: We identified 14 trials assessing ezetimibe and PCSK9 inhibitors among 83 660 adults using statins. Adding ezetimibe to statins reduced MI (RR 0.87 (95% confidence interval 0.80 to 0.94)) and stroke (RR 0.82 (0.71 to 0.96)) but not all-cause mortality (RR 0.99 (0.92 to 1.06)) or cardiovascular mortality (RR 0.97 (0.87 to 1.09)). Similarly, adding PCSK9 inhibitor to statins reduced MI (0.81 (0.76 to 0.87)) and stroke (0.74 (0.64 to 0.85)) but not all-cause (0.95 (0.87 to 1.03)) or cardiovascular mortality (0.95 (0.87 to 1.03)). Among adults with very high cardiovascular risk, adding PCSK9 inhibitor was likely to reduce MI (16 per 1000) and stroke (21 per 1000) (moderate to high certainty); whereas adding ezetimibe was likely to reduce stroke (14 per 1000), but the reduction of MI (11 per 1000) (moderate certainty) did not reach MID. Adding ezetimibe to PCSK9 inhibitor and statin may reduce stroke (11 per 1000), but the reduction of MI (9 per 1000) (low certainty) did not reach MID. Adding PCSK9 inhibitors to statins and ezetimibe may reduce MI (14 per 1000) and stroke (17 per 1000) (low certainty). Among adults with high cardiovascular risk, adding PCSK9 inhibitor probably reduced MI (12 per 1000) and stroke (16 per 1000) (moderate certainty); adding ezetimibe probably reduced stroke (11 per 1000), but the reduction in MI did not achieve MID (8 per 1000) (moderate certainty). Adding ezetimibe to PCSK9 inhibitor and statins did not reduce outcomes beyond MID, while adding PCSK9 inhibitor to ezetimibe and statins may reduce stroke (13 per 1000). These effects were consistent in statin-intolerant patients. Among moderate and low cardiovascular risk groups, adding PCSK9 inhibitor or ezetimibe to statins yielded little or no benefit for MI and stroke. CONCLUSIONS: Ezetimibe or PCSK9 inhibitors may reduce non-fatal MI and stroke in adults at very high or high cardiovascular risk who are receiving maximally tolerated statin therapy or are statin-intolerant, but not in those with moderate and low cardiovascular risk.


Assuntos
Anticolesterolemiantes , Doenças Cardiovasculares , Inibidores de Hidroximetilglutaril-CoA Redutases , Infarto do Miocárdio , Acidente Vascular Cerebral , Adulto , Anticolesterolemiantes/efeitos adversos , Doenças Cardiovasculares/induzido quimicamente , Doenças Cardiovasculares/prevenção & controle , Ezetimiba/uso terapêutico , Fatores de Risco de Doenças Cardíacas , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Infarto do Miocárdio/induzido quimicamente , Infarto do Miocárdio/prevenção & controle , Metanálise em Rede , Inibidores de PCSK9 , Pró-Proteína Convertase 9 , Fatores de Risco , Acidente Vascular Cerebral/induzido quimicamente , Acidente Vascular Cerebral/prevenção & controle
20.
Diabetes Obes Metab ; 24(10): 1927-1938, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-35589614

RESUMO

AIM: To assess the effects of canagliflozin on the incidence of atrial fibrillation/atrial flutter (AF/AFL) and other key cardiorenal outcomes in a pooled analysis of the CANVAS and CREDENCE trials. MATERIALS AND METHODS: Participants with type 2 diabetes and high risk of cardiovascular disease or chronic kidney disease were included and randomly assigned to canagliflozin or placebo. We explored the effects of canagliflozin on the incidence of first AF/AFL events and AF/AFL-related complications (ischaemic stroke/transient ischaemic attack/hospitalization for heart failure). Major adverse cardiovascular events and a renal-specific outcome by baseline AF/AFL status were analysed using Cox regression models. RESULTS: Overall, 354 participants experienced a first AF/AFL event. Canagliflozin had no detectable effect on AF/AFL (hazard ratio [HR] 0.82, 95% confidence interval [CI] 0.67-1.02) compared with placebo. Subgroup analysis, however, suggested a possible reduction in AF/AFL in those with no AF/AFL history (HR 0.78, 95% CI 0.62-0.99). Canagliflozin was also associated with a reduction in AF/AFL-related complications (HR 0.74, 95% CI 0.65-0.86). There was no evidence of treatment heterogeneity by baseline AF/AFL history for other key cardiorenal outcomes (all Pinteraction > 0.14). Meta-analysis of five sodium-glucose cotransporter-2 (SGLT2) inhibitor trials demonstrated a 19% reduction in AF/AFL events with active treatment (HR 0.81, 95% CI 0.72-0.92). CONCLUSIONS: Overall, a significant effect of canagliflozin on the incidence of AF/AFL events could not be shown, however, a possible reduction in AF/AFL events in those with no prior history requires further investigation. Meta-analysis suggests SGLT2 inhibition reduces AF/AFL incidence.


Assuntos
Fibrilação Atrial , Flutter Atrial , Isquemia Encefálica , Diabetes Mellitus Tipo 2 , Acidente Vascular Cerebral , Fibrilação Atrial/complicações , Fibrilação Atrial/tratamento farmacológico , Fibrilação Atrial/epidemiologia , Flutter Atrial/complicações , Flutter Atrial/tratamento farmacológico , Flutter Atrial/epidemiologia , Canagliflozina/efeitos adversos , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/epidemiologia , Humanos , Transportador 2 de Glucose-Sódio , Acidente Vascular Cerebral/induzido quimicamente
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