ABSTRACT
BACKGROUND AND OBJECTIVES: The efficacy of sodium-glucose cotransporter-2 inhibitors (SGLT2i) may depend on renal function, and this raises theoretical concern over its effects on cardiovascular outcomes in patients with type 2 diabetes mellitus (T2DM) and chronic kidney disease (CKD). METHODS: This systematic review and updated meta-analysis of randomized controlled trials (RCTs) compared cardiovascular outcomes of patients with T2DM and CKD treated with SGLT2i to placebo. PubMed, Embase, and Cochrane were systematically searched. Prespecified subgroup analyses were performed in strata of estimated glomerular filtration rate (eGFR) of <45 mL/min/1.73 m² and 45 to 59 mL/min/1.73 m². RESULTS: Nine RCTs comprising 29,146 patients were selected. Average follow-up ranged from 0.75 to 4.2 years. SGLT2i were shown to reduce the risk of all-cause mortality (hazard ratio [HR], 0.88; 95% confidence interval [CI], 0.79-0.97; p=0.01), the composite of cardiovascular mortality or hospitalizations for heart failure (HHF: HR, 0.71; 95% CI, 0.65-0.78; p<0.001), cardiovascular mortality (HR, 0.86; 95% CI, 0.76-0.98; p=0.02), HHF (HR, 0.62; 95% CI, 0.55-0.71; p<0.001), major adverse cardiovascular events (HR, 0.85; 95% CI, 0.77-0.94; p=0.002), stroke (HR, 0.76; 95% CI, 0.59-0.97; p=0.03), and myocardial infarction (HR, 0.78; 95% CI, 0.67-0.91; p=0.001). These findings were consistent over strata of eGFR, albeit with a lower incidence of stroke in patients treated with SGLT2i with eGFR <45 mL/min/1.73 m² (p-value for interaction=0.04). CONCLUSIONS: Compared with a placebo, patients with T2DM and CKD treated with SGLT2i experience a reduction in all-cause mortality, cardiovascular mortality, and HHF. TRIAL REGISTRATION: PROSPERO Identifier: CRD42023401081.
ABSTRACT
BACKGROUND: Coronavirus disease 2019 (COVID-19) is associated with hypercoagulability. It remains uncertain whether ongoing anticoagulation for atrial fibrillation (AF) in patients who later contract COVID-19 improves clinical outcomes. OBJECTIVES: To compare chronic oral anticoagulation with no previous anticoagulation in patients with AF who contracted a COVID-19 infection concerning the outcomes of all-cause mortality, COVID-19 mortality, intensive care unit (ICU) admission, and hospitalization. METHODS: We systematically searched PubMed, Embase, and Cochrane Library for eligible studies from inception to December 2022. We included studies comparing COVID-19 outcomes in patients with versus without prior chronic anticoagulation for AF. Risk ratios (RR) with 95% confidence intervals (CI) were pooled with a random-effects model. The level of significance was set at p < 0.05. Quality assessment and risk of bias were performed according to Cochrane recommendations. RESULTS: Ten studies comprising 1,177,858 patients with COVID-19 and AF were identified, of whom 893,772 (75.9%) were on prior chronic anticoagulation for AF. In patients with COVID-19, being on chronic anticoagulation for AF significantly reduced all-cause mortality (RR 0.75; 95% CI 0.57 to 0.99; p = 0.048; I2 = 89%) and COVID-19-related mortality (RR 0.76; 95% CI 0.72 to 0.79; p < 0.001; I2 = 0%) when compared with no prior anticoagulation. In contrast, there was no difference between groups regarding hospitalization (RR 1.08; 95% CI 0.82 to 1.41; p = 0.587; I2 = 95%) or ICU admission (RR 0.86; 95% CI 0.68 to 1.09; p = 0.216; I2 = 69%). CONCLUSIONS: In this meta-analysis, chronic anticoagulation for patients with AF who contracted COVID-19 was associated with significantly lower rates of all-cause mortality and COVID-19-related mortality as compared with no previous anticoagulation.
FUNDAMENTO: A doença por coronavírus 2019 (COVID-19) está associada à hipercoagulabilidade. Permanece incerto se a anticoagulação contínua para fibrilação atrial (FA) em pacientes que posteriormente contraem COVID-19 melhora os desfechos clínicos. OBJETIVOS: Comparar a anticoagulação oral crônica com ausência de anticoagulação prévia em pacientes com FA que contraíram uma infecção por COVID-19 em relação aos desfechos de mortalidade por todas as causas, mortalidade por COVID-19, admissão em unidade de terapia intensiva (UTI) e hospitalização. MÉTODOS: Buscamos sistematicamente no PubMed, Embase e Cochrane Library estudos elegíveis desde o início até dezembro de 2022. Incluímos estudos que compararam desfechos de COVID-19 em pacientes com e sem anticoagulação crônica prévia para FA. Foram agrupadas razões de risco (RR) com intervalos de confiança (IC) de 95% por meio de um modelo de efeitos aleatórios. O nível de significância foi estabelecido em p < 0,05. As avaliações da qualidade e do risco de viés foram realizadas de acordo com as recomendações da Cochrane. RESULTADOS: Foram identificados 10 estudos abrangendo 1.177.858 pacientes com COVID-19 e FA, dos quais 893.772 (75,9%) estavam em anticoagulação crônica prévia para FA. Em pacientes com COVID-19, a anticoagulação crônica para FA reduziu significativamente a mortalidade por todas as causas (RR 0,75; IC 95% 0,57 a 0,99; p = 0,048; I2 = 89%) e a mortalidade relacionada à COVID-19 (RR 0,76; IC 95% 0,72 a 0,79; p < 0,001; I2 = 0%) quando comparada com a ausência de anticoagulação prévia. Em contrapartida, não houve diferença entre os grupos em relação à hospitalização (RR 1,08; IC 95% 0,82 a 1,41; p = 0,587; I2 = 95%) ou internação em UTI (RR 0,86; IC 95% 0,68 a 1,09; p = 0,216; I2 = 69%). CONCLUSÕES: Nesta metanálise, a anticoagulação crônica para pacientes com FA que contraíram COVID-19 foi associada a taxas significativamente mais baixas de mortalidade por todas as causas e mortalidade relacionada à COVID-19 em comparação com a ausência de anticoagulação anterior.
Subject(s)
Anticoagulants , Atrial Fibrillation , COVID-19 , Humans , Atrial Fibrillation/drug therapy , Atrial Fibrillation/mortality , Atrial Fibrillation/complications , COVID-19/mortality , COVID-19/complications , Anticoagulants/therapeutic use , Anticoagulants/administration & dosage , Hospitalization/statistics & numerical data , SARS-CoV-2 , Intensive Care UnitsABSTRACT
Atherosclerosis is an inflammatory disease. Coronary artery calcium (CAC) is a marker of atherosclerotic disease events and mortality risk. Increased GlycA, an emerging marker of inflammation, is associated with a higher risk for coronary artery disease (CAD). However, there is conflicting evidence on whether GlycA predicts subclinical CAD progression. We hypothesized that GlycA can predict subclinical CAC incidence/progression in healthy participants. We included 2,690 ELSA-Brasil cohort participants without cardiovascular/chronic inflammatory disease not receiving statin therapy who had GlycA levels measured and 2 interval CAC assessments between 2010 and 2018. Multivariable logistic and linear regression models were computed to evaluate GlycA as a predictor of CAC incidence and progression. CAC incidence required a baseline CAC of 0. CAC progression required a baseline CAC >0. The mean age of participants was 48.6 ± 7.7 years, 56.7% were women, and 54.6% and 16.1% (429 of 2,690) were White and Black, respectively. The mean CAC interscan period was 5.1 ± 0.9 years, the mean GlycA level was 414.7 ± 65 µmol/L, and the incidence of CAC was 13.1% (280 of 2,129). The GlycA level odds ratio for CAC incidence was 1.002 (95% confidence interval 1.0005 to 1.005, p = 0.016), adjusted for demographics, lifestyle, a family history of early CAD (≤60 years), lipids, and co-morbidities. The GlycA (≤p25 vs ≥p75) odds ratio for CAC progression (Berry definition) was 1.77 (95% confidence interval 1.07 to 2.96, p = 0.03) in a similar multivariable-adjusted model. Higher GlycA levels were associated with CAC incidence and progression in a healthy Brazilian cohort.
Subject(s)
Coronary Artery Disease , Disease Progression , Vascular Calcification , Humans , Female , Male , Middle Aged , Incidence , Coronary Artery Disease/epidemiology , Vascular Calcification/epidemiology , Vascular Calcification/diagnostic imaging , Brazil/epidemiology , Biomarkers/blood , Longitudinal Studies , Adult , Risk FactorsABSTRACT
Resumo Fundamento: A doença por coronavírus 2019 (COVID-19) está associada à hipercoagulabilidade. Permanece incerto se a anticoagulação contínua para fibrilação atrial (FA) em pacientes que posteriormente contraem COVID-19 melhora os desfechos clínicos. Objetivos: Comparar a anticoagulação oral crônica com ausência de anticoagulação prévia em pacientes com FA que contraíram uma infecção por COVID-19 em relação aos desfechos de mortalidade por todas as causas, mortalidade por COVID-19, admissão em unidade de terapia intensiva (UTI) e hospitalização. Métodos: Buscamos sistematicamente no PubMed, Embase e Cochrane Library estudos elegíveis desde o início até dezembro de 2022. Incluímos estudos que compararam desfechos de COVID-19 em pacientes com e sem anticoagulação crônica prévia para FA. Foram agrupadas razões de risco (RR) com intervalos de confiança (IC) de 95% por meio de um modelo de efeitos aleatórios. O nível de significância foi estabelecido em p < 0,05. As avaliações da qualidade e do risco de viés foram realizadas de acordo com as recomendações da Cochrane. Resultados: Foram identificados 10 estudos abrangendo 1.177.858 pacientes com COVID-19 e FA, dos quais 893.772 (75,9%) estavam em anticoagulação crônica prévia para FA. Em pacientes com COVID-19, a anticoagulação crônica para FA reduziu significativamente a mortalidade por todas as causas (RR 0,75; IC 95% 0,57 a 0,99; p = 0,048; I2 = 89%) e a mortalidade relacionada à COVID-19 (RR 0,76; IC 95% 0,72 a 0,79; p < 0,001; I2 = 0%) quando comparada com a ausência de anticoagulação prévia. Em contrapartida, não houve diferença entre os grupos em relação à hospitalização (RR 1,08; IC 95% 0,82 a 1,41; p = 0,587; I2 = 95%) ou internação em UTI (RR 0,86; IC 95% 0,68 a 1,09; p = 0,216; I2 = 69%). Conclusões: Nesta metanálise, a anticoagulação crônica para pacientes com FA que contraíram COVID-19 foi associada a taxas significativamente mais baixas de mortalidade por todas as causas e mortalidade relacionada à COVID-19 em comparação com a ausência de anticoagulação anterior.
Abstract Background: Coronavirus disease 2019 (COVID-19) is associated with hypercoagulability. It remains uncertain whether ongoing anticoagulation for atrial fibrillation (AF) in patients who later contract COVID-19 improves clinical outcomes. Objectives: To compare chronic oral anticoagulation with no previous anticoagulation in patients with AF who contracted a COVID-19 infection concerning the outcomes of all-cause mortality, COVID-19 mortality, intensive care unit (ICU) admission, and hospitalization. Methods: We systematically searched PubMed, Embase, and Cochrane Library for eligible studies from inception to December 2022. We included studies comparing COVID-19 outcomes in patients with versus without prior chronic anticoagulation for AF. Risk ratios (RR) with 95% confidence intervals (CI) were pooled with a random-effects model. The level of significance was set at p < 0.05. Quality assessment and risk of bias were performed according to Cochrane recommendations. Results: Ten studies comprising 1,177,858 patients with COVID-19 and AF were identified, of whom 893,772 (75.9%) were on prior chronic anticoagulation for AF. In patients with COVID-19, being on chronic anticoagulation for AF significantly reduced all-cause mortality (RR 0.75; 95% CI 0.57 to 0.99; p = 0.048; I2 = 89%) and COVID-19-related mortality (RR 0.76; 95% CI 0.72 to 0.79; p < 0.001; I2 = 0%) when compared with no prior anticoagulation. In contrast, there was no difference between groups regarding hospitalization (RR 1.08; 95% CI 0.82 to 1.41; p = 0.587; I2 = 95%) or ICU admission (RR 0.86; 95% CI 0.68 to 1.09; p = 0.216; I2 = 69%). Conclusions: In this meta-analysis, chronic anticoagulation for patients with AF who contracted COVID-19 was associated with significantly lower rates of all-cause mortality and COVID-19-related mortality as compared with no previous anticoagulation.
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BACKGROUND: Coronary computed tomography angiogram (CCTA) is a crucial tool for diagnosing CAD, but its impact on altering preventive medications is not well-documented. This systematic review aimed to compare changes in aspirin and statin therapy following CCTA and functional stress testing in patients with suspected CAD, and in those underwent CCTA when stratified by the presence/absence of plaque. RESULTS: Eight studies involving 42,812 CCTA patients and 64,118 cardiac stress testing patients were analyzed. Compared to functional testing, CCTA led to 66 â% more changes in statin therapy (pooled RR, 95 â% CI [1.28-2.15]) and a 74 â% increase in aspirin prescriptions (pooled RR, 95 â% CI [1.34-2.26]). For medication modifications based on CCTA results, 13 studies (47,112 patients with statin data) and 11 studies (12,089 patients with aspirin data) were included. Patients with any plaque on CCTA were five times more likely to use or intensify statins compared to those without CAD (pooled RR, 5.40, 95 â% CI [4.16-7.00]). Significant heterogeneity remained, which decreased when stratified by diabetes rates. Aspirin use increased eightfold after plaque detection (pooled RR, 8.94 [95 â% CI, 4.21-19.01]), especially with obstructive plaque findings (pooled RR, 9.41, 95 â% CI [2.80-39.02]). CONCLUSION: In conclusion, CCTA resulted in higher changes in statin and aspirin therapy compared to cardiac stress testing. Detection of plaque by CCTA significantly increased statin and aspirin therapy.
Subject(s)
Aspirin , Computed Tomography Angiography , Coronary Angiography , Coronary Artery Disease , Hydroxymethylglutaryl-CoA Reductase Inhibitors , Platelet Aggregation Inhibitors , Predictive Value of Tests , Aged , Female , Humans , Male , Middle Aged , Angina Pectoris/diagnostic imaging , Aspirin/therapeutic use , Coronary Artery Disease/diagnostic imaging , Coronary Vessels/diagnostic imaging , Exercise Test , Hydroxymethylglutaryl-CoA Reductase Inhibitors/therapeutic use , Plaque, Atherosclerotic , Platelet Aggregation Inhibitors/therapeutic use , Practice Patterns, Physicians' , Risk Factors , Treatment OutcomeABSTRACT
In patients with stable atherosclerotic cardiovascular disease, proprotein convertase subtilisin/kexin type 9 inhibitors (PCSK9is) have shown a 50% to 60% reduction in low-density lipoprotein cholesterol (LDL-C) from baseline when added to high-intensity statin therapy. However, less is known about the impact of PCSK9is in the setting of an acute coronary syndrome (ACS). Therefore, we performed a systematic review and meta-analysis comparing PCSK9is with placebo in the setting of ACS added to guideline-directed high-intensity or maximally tolerated statin therapy. We included randomized controlled trials with initiation of a PCSK9i or placebo within 1 week of presentation or percutaneous coronary intervention for ACS. PubMed, EMBASE, and Cochrane Central were searched. This study followed the Cochrane and Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) recommendations. A total of 6 randomized controlled trials were included, with a total of 996 patients, of whom 503 (50.5%) received PCSK9is. The mean follow-up ranged from 4 to 52 weeks. The LDL-C (mean difference [MD] -44.0 mg/100 ml, CI -54.3 to -33.8, p <0.001) and lipoprotein (a) levels (MD -24.0 nmol/L, confidence interval [CI] -43.0 to -4.9, pâ¯=â¯0.01) were significantly lower at follow-up with PCSK9is. Similarly, the total cholesterol (MD -49.2 mg/100 ml, CI -59.0 to -39.3), triglycerides (MD -19.0 mg/100 ml, CI -29.9 to -8.2), and apolipoprotein B (MD -33.3 mg/100 ml, CI -44.4 to -22.1) were significantly reduced with PCSK9is. In conclusion, in patients with ACS, early initiation of PCSK9i added to statin significantly reduces LDL-C and lipoprotein (a) levels compared with placebo. Whether the differences in these atherogenic lipoproteins translate into a reduction in clinical end points is yet to be determined.
Subject(s)
Acute Coronary Syndrome , Anticholesteremic Agents , Atherosclerosis , Hydroxymethylglutaryl-CoA Reductase Inhibitors , Humans , Hydroxymethylglutaryl-CoA Reductase Inhibitors/therapeutic use , Cholesterol, LDL , Proprotein Convertase 9 , PCSK9 Inhibitors , Acute Coronary Syndrome/drug therapy , Atherosclerosis/drug therapy , Lipoprotein(a) , Anticholesteremic Agents/therapeutic useABSTRACT
BACKGROUND: The optimal antithrombotic therapy following left atrial appendage occlusion (LAAO) in patients with nonvalvular atrial fibrillation (AF) remains uncertain. OBJECTIVES: In this study, the authors sought to compare the efficacy and safety of various antithrombotic strategies after LAAO. METHODS: We searched the Medline, Cochrane, EMBASE, LILACS, and ClinicalTrials.gov databases for studies reporting outcomes after LAAO, stratified by antithrombotic therapy prescribed at postprocedural discharge. Direct oral anticoagulants (DOACs), vitamin K antagonists (VKAs), single antiplatelet therapy (SAPT), dual antiplatelet therapy (DAPT), DOAC plus SAPT, VKA plus SAPT, and no antithrombotic therapy were analyzed. We performed a frequentist random effects model network meta-analysis to estimate the OR and 95% CI for each comparison. P-scores provided a ranking of treatments. RESULTS: Forty-one studies comprising 12,451 patients with nonvalvular AF were included. DAPT, DOAC, DOAC plus SAPT, and VKA were significantly superior to no therapy to prevent device-related thrombosis. DOAC was associated with lower all-cause mortality than VKA (OR: 0.39; 95% CI: 0.17-0.89; P = 0.03). Compared with SAPT, DAPT was associated with fewer thromboembolic events (OR: 0.50; 95% CI: 0.29-0.88; P = 0.02), without a difference in major bleeding. In the analysis of P-scores, DOAC monotherapy was the strategy most likely to have lower thromboembolic events and major bleeding. CONCLUSIONS: In this network meta-analysis comparing initial antithrombotic therapies after LAAO, monotherapy with DOAC had the highest likelihood of lower thromboembolic events and major bleeding. DAPT was associated with a lower incidence of thromboembolic events compared with SAPT and may be a preferred option in patients unable to tolerate anticoagulation.
Subject(s)
Atrial Appendage , Atrial Fibrillation , Stroke , Thromboembolism , Humans , Platelet Aggregation Inhibitors , Fibrinolytic Agents/therapeutic use , Atrial Appendage/surgery , Network Meta-Analysis , Anticoagulants , Hemorrhage/etiology , Atrial Fibrillation/complications , Atrial Fibrillation/drug therapy , Thromboembolism/epidemiology , Thromboembolism/etiology , Thromboembolism/prevention & control , Stroke/etiology , Treatment OutcomeABSTRACT
OBJECTIVES: Tirzepatide is a dual glucose-dependent insulinotropic polypeptide and glucagon-like peptide-1 receptor agonist approved for type 2 diabetes. We performed a meta-analysis to assess tirzepatide's weight reduction efficacy and safety. METHODS: We searched PubMed, Embase, and Cochrane for randomized controlled trials published from inception to July 2022, comparing tirzepatide with placebo for the co-primary endpoints of absolute and percent change in weight. Mean difference (MD) and odds ratio (OR) were calculated for continuous and binary outcomes, respectively. Review Manager 5.4.1 and RStudio were used for the statistical analysis, and RoB-2 (Cochrane) to assess the risk of bias. RESULTS: Of 397 search results, 6 studies (4036 participants) ranging from 12 to 72 weeks were included. Pooled analysis showed that tirzepatide 5 mg, 10 mg, and 15 mg were more effective than placebo, with MD in body weight of -7.7 kg (95% CI -11.0, -4.4; p < 0.001), -11.6 kg (95% CI -18.8, -4.3; p = 0.002), and -11.8 kg (95% CI -17.4, -6.2; p < 0.001), respectively, and MD in percent change in weight of -8.1% (95% CI -11.0, -5.2; p < 0.001), -11.9% (95% CI -18.1, -5.6; p < 0.001), and -12.4% (95% CI -17.2, -7.5; p < 0.001), respectively. Tirzepatide also reduced BMI and waist circumference. Adverse events were more common with tirzepatide with respect to nausea (OR 4.2; 95% CI 2.4, 7.5; p < 0.001), vomiting (OR 7.0; 95% CI 4.3, 11.4; p < 0.001), and diarrhea (OR 2.8; 95% CI 1.6, 4.9; p < 0.001) (15 mg dose), when compared with placebo. CONCLUSIONS: The results support that tirzepatide leads to substantial weight reduction and constitutes a valuable therapeutic option for weight management, despite an increase in gastrointestinal symptoms. PROTOCOL REGISTRATION: CRD42022348576.
Subject(s)
Diabetes Mellitus, Type 2 , Humans , Diabetes Mellitus, Type 2/drug therapy , Glucagon-Like Peptide-1 Receptor/agonists , Randomized Controlled Trials as Topic , Gastric Inhibitory Polypeptide , Weight Loss , Hypoglycemic Agents/pharmacology , Hypoglycemic Agents/therapeutic useABSTRACT
AIMS: We aimed to perform a systematic review and meta-analysis of randomized controlled trials (RCTs) to determine the impact of a polypill-based strategy (PBS) on therapeutic adherence and cardiovascular outcomes compared with usual care for secondary prevention of cardiovascular diseases (CVDs). METHODS AND RESULTS: We systematically searched PubMed, Cochrane, and Scopus databases from inception to January 2023, including RCTs comparing PBS with usual care in patients with prior CVD. We assessed efficacy outcomes of therapeutic adherence, systolic blood pressure (SBP), and LDL-cholesterol (LDL-C) and safety outcomes of all-cause and cardiovascular mortality. Statistical analysis was performed with Review Manager 5.4.1 and R Version 4.2.1. A total of 8 RCTs with a population of 6541 individuals were included, of whom 3318 (50.7%) were treated with the PBS. Follow-up ranged from 6 to 60 months. The polypill-based strategy was associated with a significantly increased therapeutic adherence [risk ratio (RR) 1.22; 95% confidence interval (CI) 1.10-1.34; P < 0.001]. Cardiovascular mortality (RR 0.61; 95% CI 0.44-0.85; P = 0.004), SBP [mean difference (MD) -1.47 mmHg; 95% CI -2.86 to -0.09; P = 0.04], and LDL-C (MD -3.83 mg/dL; 95% CI -6.99 to -0.67; P = 0.02) were significantly lower in the PBS group. The incidence of all-cause mortality was similar between groups (RR 0.83; 95% CI 0.54-1.29; P = 0.41). CONCLUSION: In patients with pre-existing CVD, a PBS is associated with lower cardiovascular mortality and improved therapeutic adherence, along with a modest decrease in SBP and LDL-C compared with usual care. Thus, a PBS may be considered a preferred option for this patient population.
Adherence to medical therapy plays a critical role in the prevention of atherosclerotic events. Previous studies have shown that a polypill-based strategy (PBS) increases treatment adherence in the context of primary prevention of cardiovascular diseases. However, the effectiveness of this strategy in secondary prevention is yet to be determined. Herein, we demonstrate the following: Polypill-based strategy improved therapeutic adherence and reduced LDL-cholesterol and systolic blood pressure levels.There was a reduction in cardiovascular mortality with the use of the PBS; however, no significant difference was found in all-cause mortality between groups.
Subject(s)
Cardiovascular Diseases , Humans , Blood Pressure , Cardiovascular Diseases/diagnosis , Cardiovascular Diseases/prevention & control , Cardiovascular Diseases/epidemiology , Cholesterol, LDL , Randomized Controlled Trials as Topic , Secondary Prevention/methodsABSTRACT
BACKGROUND: Pretreatment with oral P2Y12 inhibitors is a standard practice for ST-elevation myocardial infarction (STEMI) patients undergoing percutaneous coronary intervention (PCI). However, the efficacy and safety of P2Y12 inhibitors pretreatment remain unclear. OBJECTIVES: We conducted a meta-analysis to investigate the impact of P2Y12 inhibitor pretreatment on thrombotic and hemorrhagic endpoints in STEMI patients. METHODS: We searched multiple databases for studies that compared P2Y12 inhibitor pretreatment with no pretreatment in STEMI patients and reported endpoints of interest. Random effects model was used for the meta-analysis. RESULTS: Our meta-analysis included 3 randomized controlled trials and 14 observational studies, comprising 70,465 patients assigned to either P2Y12 inhibitor pretreatment (50,328 patients) or no pretreatment (20,137 patients). Compared to no pretreatment, P2Y12 inhibitor pretreatment did not result in significant reductions in all-cause mortality (risk ratio [RR] 0.73; 95% confidence interval [CI]: 0.52-1.03; p = 0.07), myocardial infarction (RR 0.75; 95% CI: 0.53-1.07; p = 0.11), or major bleeding (RR 0.80; 95% CI: 0.56-1.16; p = 0.22) at 30 days. However, our subgroup analysis revealed that P2Y12 inhibitor pretreatment administered in the pre-hospital setting was associated with a significant reduction in the incidence of myocardial infarction compared to no pretreatment (RR 0.73; 95% CI: 0.56-0.91; p < 0.01). CONCLUSION: Our analysis suggests that pretreatment with oral P2Y12 inhibitors before PCI in patients with STEMI was not associated with reduced all-cause mortality, myocardial infarction, or major bleeding. However, pretreatment with P2Y12 inhibitors in the pre-hospital setting appears to be beneficial in reducing reinfarction.
Subject(s)
Myocardial Infarction , Percutaneous Coronary Intervention , ST Elevation Myocardial Infarction , Humans , ST Elevation Myocardial Infarction/diagnostic imaging , ST Elevation Myocardial Infarction/therapy , Platelet Aggregation Inhibitors/adverse effects , Percutaneous Coronary Intervention/adverse effects , Treatment Outcome , Myocardial Infarction/etiology , Hemorrhage/chemically induced , Purinergic P2Y Receptor Antagonists/adverse effects , Observational Studies as TopicABSTRACT
BACKGROUND: We sought to compare cardiovascular outcomes, renal function, and diuresis in patients receiving standard diuretic therapy for acute heart failure (AHF) with or without the addition of SGLT2i. METHODS AND RESULTS: Systematic search of three electronic databases identified nine eligible randomized controlled trials involving 2,824 patients. The addition of SGLT2i to conventional therapy for AHF reduced all-cause death (odds ratio [OR] 0.75; 95% CI 0.56-0.99; p = 0.049), readmissions for heart failure (HF) (OR 0.54; 95% CI 0.44-0.66; p < 0.001), and the composite of cardiovascular death and readmissions for HF (hazard ratio 0.71; 95% CI 0.60-0.84; p < 0.001). Furthermore, SGLT2i increased mean daily urinary output in liters (mean difference [MD] 0.45; 95% CI 0.03-0.87; p = 0.035) and decreased mean daily doses of loop diuretics in mg of furosemide equivalent (MD -34.90; 95% CI [- 52.58, - 17.21]; p < 0.001) without increasing the incidence worsening renal function (OR 0.75; 95% CI 0.43-1.29; p = 0.290). CONCLUSION: SGLT2i addition to conventional diuretic therapy reduced all-cause death, readmissions for HF, and the composite of cardiovascular death or readmissions for HF. Moreover, SGLT2i was associated with a higher volume of diuresis with a lower dose of loop diuretics.
Subject(s)
Diabetes Mellitus, Type 2 , Heart Failure , Sodium-Glucose Transporter 2 Inhibitors , Humans , Diabetes Mellitus, Type 2/complications , Diuretics/adverse effects , Diuretics/pharmacology , Diuretics/therapeutic use , Heart Failure/drug therapy , Kidney/drug effects , Randomized Controlled Trials as Topic , Sodium Potassium Chloride Symporter Inhibitors , Sodium-Glucose Transporter 2 Inhibitors/adverse effects , Sodium-Glucose Transporter 2 Inhibitors/pharmacology , Sodium-Glucose Transporter 2 Inhibitors/therapeutic useABSTRACT
Background: Electrocardiographic (ECG) criteria to detect left ventricular hypertrophy (LVH) in patients with left bundle branch block (LBBB) remain under debate. We conducted a systematic review and meta-analysis to evaluate the diagnostic accuracy of different ECG criteria for diagnosing LVH in patients with LBBB. Methods: We searched PubMed, Embase, Cochrane, and LILACS for articles evaluating the diagnostic accuracy of ECG criteria for LVH in patients with LBBB published between 1984 and 2023. Echocardiogram, magnetic resonance imaging, or autopsy were used as the reference standard for diagnosis of LVH. Risk of bias was assessed using the Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2) tool. The co-primary outcomes were sensitivity, specificity, the diagnostic odds ratio, and likelihood ratios, estimated using a bivariate generalized linear mixed model for each ECG criterion. The prespecified protocol was registered in the International Prospective Register of Systematic Reviews (PROSPERO). Results: We included 12 studies with a total of 1023 patients. We analyzed 10 criteria for LVH on ECG, including the Sokolow-Lyon criterion, the Cornell criterion, the RaVL (R wave in aVL) criterion, the Gubner-Ungerleider criterion, and the Dálfo criterion, among others. The Dalfó criterion was used for 487 patients and had the highest pooled sensitivity of 86% (95% confidence interval [CI] 57%-97%). All the other criteria had poor sensitivities. The Gubner-Ungerleider criterion and the RV5 or RV6 > 25 mm criterion had the highest specificities, with the former being used for 805 patients, obtaining a specificity of 99% (95% CI 80%-100%) and the latter being used for 355 patients, obtaining a specificity of 99% (95% CI 94%-100%). Conclusions: In patients with LBBB, the use of ECG criteria had poor performance for ruling out LVH, mostly due to low sensitivities. None of the criteria analyzed demonstrated a balanced tradeoff between sensitivity and specificity, suggesting that ECG should not be used routinely to screen for LVH.
Contexte: Les critères électrocardiographiques (ECG) visant à détecter une hypertrophie ventriculaire gauche (HVG) chez les patients présentant un bloc de branche gauche (BBG) font encore l'objet de discussions. Nous avons réalisé une synthèse des publications et une méta-analyse afin d'évaluer l'exactitude diagnostique de différents critères ECG pour le diagnostic de l'HVG chez les patients présentant un BBG. Méthodologie: Nous avons effectué une recherche dans les bases de données PubMed, Embase, Cochrane et LILACS afin de recenser les articles publiés entre 1984 et 2023 portant sur l'évaluation de l'exactitude de critères ECG pour le diagnostic d'une HVG chez les patients présentant un BBG. L'échocardiographie, l'imagerie par résonance magnétique et l'autopsie ont servi de normes de référence pour le diagnostic de l'HVG. Le risque de biais a été évalué au moyen de l'outil QUADAS-2 (Quality Assessment of Diagnostic Accuracy Studies). Les principaux critères d'évaluation étaient la sensibilité, la spécificité, le risque relatif approché diagnostique et les rapports de vraisemblance, estimés au moyen d'un modèle linéaire mixte généralisé à deux variables pour chaque critère ECG. Le protocole défini au préalable a été enregistré dans le registre international de revues systématiques prospectives PROSPERO. Résultats: Nous avons recensé 12 études, comptant au total 1 023 patients. Nous avons analysé 10 critères pour le diagnostic d'HVG à l'ECG, notamment l'indice de Sokolow-Lyon, l'indice de Cornell, l'onde R en aVL, l'indice de Gubner-Ungerleider et l'indice de Dálfo. Ce dernier a été utilisé pour 487 patients et avait la sensibilité regroupée la plus élevée, soit 86 % (intervalle de confiance [IC] à 95 % : 57-97 %). La sensibilité de tous les autres critères était faible. L'indice de Gubner-Ungerleider et le critère de l'onde R en V5 ou V6 > 25 mm étaient associés aux spécificités les plus élevées. Le premier a été utilisé pour 805 patients et présentait une spécificité de 99 % (IC à 95 % : 80-100 %). Le second a été utilisé pour 355 patients et présentait une spécificité de 99 % (IC à 95 % : 94-100 %). Conclusions: Chez les patients présentant un BBG, l'utilisation de critères ECG a été associée à un rendement médiocre pour exclure un diagnostic d'HVG, principalement en raison de la faible sensibilité de ces critères. Aucun des critères analysés n'offrait un compromis équilibré entre la sensibilité et la spécificité, ce qui porte à croire que l'ECG ne devrait pas être utilisée systématiquement pour dépister une HVG.
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BACKGROUND: The efficacy and safety of percutaneous coronary interventions (PCI) relative to coronary artery bypass grafting (CABG) in patients with diabetes and unprotected left main coronary artery disease (LMCAD) are not well established. OBJECTIVES: To perform a meta-analysis evaluating the long-term outcomes after PCI with drug-eluting stents (DES), as compared with CABG, in patients with diabetes and unprotected LMCAD. METHODS: MEDLINE, Cochrane, and Embase were searched for randomized controlled trials (RCTs) that reported outcomes after PCI with DES versus CABG in unprotected LMCAD among patients with diabetes. To evaluate the long-term effects of these interventions, we restricted this analysis to studies with a minimum follow-up period of 3 years. Risk ratios (RRs) with 95% confidence intervals (CIs) were pooled with a random-effects model. Quality assessment and risk of bias were performed according to Cochrane recommendations. RESULTS: Four RCTs with a total of 1080 patients were included, 553 (51.2%) of whom underwent PCI. There was no difference for individual outcomes of all-cause mortality (RR: 1.21; 95% CI: 0.86-1.71; p = .27; I2 = 28%), cardiovascular death (RR 1.29; 95% CI: 0.76-2.18; p = .34; I2 = 0%), or myocardial infarction (MI) (RR: 0.94; 95% CI: 0.61-1.45; p = .79; I2 = 0%). However, the risk of stroke was reduced with PCI relative to CABG (RR: 0.41; 95% CI: 0.18-0.94; p = .04; I2 = 0%), whereas the risk of any repeat revascularization was higher in the PCI group (RR: 1.99; 95% CI: 1.44-2.75; p < .001; I2 = 0%). The risk of the composite outcome of all-cause mortality, MI, stroke, or repeat revascularization was higher after PCI compared with CABG (RR: 1.30; 95% CI: 1.09-1.56; p = .004; I2 = 0%). CONCLUSION: In this meta-analysis with more than 1000 patients with diabetes and unprotected LMCAD followed for a minimum of 3 years, the incidence of repeat revascularization was higher among those treated with PCI, whereas the risk of stroke was higher in patients treated with CABG.
Subject(s)
Coronary Artery Disease , Diabetes Mellitus , Drug-Eluting Stents , Myocardial Infarction , Percutaneous Coronary Intervention , Stroke , Humans , Coronary Artery Disease/complications , Coronary Artery Disease/surgery , Drug-Eluting Stents/adverse effects , Treatment Outcome , Randomized Controlled Trials as Topic , Myocardial Infarction/etiology , Myocardial Infarction/complications , Diabetes Mellitus/epidemiology , Percutaneous Coronary Intervention/adverse effects , Stroke/epidemiology , Stroke/etiologyABSTRACT
BACKGROUND: Catheter ablation is a well-established therapy for rhythm control in patients who are refractory or intolerant to anti-arrhythmic drugs (AAD). Less is known about the efficacy of catheter ablation compared with AAD as a first-line strategy for rhythm control in atrial fibrillation (AF). OBJECTIVES: We aimed to perform a systematic review and meta-analysis of catheter ablation vs. AAD in patients naïve to prior rhythm control therapies. METHODS: PubMed, EMBASE, and Cochrane databases were searched for randomized controlled trials that compared catheter ablation to AAD for initial rhythm control in symptomatic AF and reported the outcomes of (1) recurrent atrial tachyarrhythmias (ATs); (2) symptomatic AF; (3) hospitalizations; and (4) symptomatic bradycardia. Heterogeneity was examined with I2statistics. P values of < 0.05 were considered statistically significant. RESULTS: We included five trials with 994 patients, of whom 502 (50.5%) underwent catheter ablation. Mean follow-up ranged from one to five years. Recurrences of AT (OR 0.36; 95% CI 0.25-0.52; p<0.001) and symptomatic AF (OR 0.32; 95% CI 0.18-0.57; p<0.001), and hospitalizations (OR 0.25; 95% CI 0.15-0.42; p<0.001) were significantly less frequent in patients treated with catheter ablation compared with AAD. Symptomatic bradycardia was not significantly different between groups (OR 0.55; 95% CI 0.18-1.65; p=0.28). Significant pericardial effusions or tamponade occurred in eight of 464 (1.7%) patients in the catheter ablation group. CONCLUSION: These findings suggest that catheter ablation has superior efficacy to AAD as an initial rhythm control strategy in patients with symptomatic AF.
FUNDAMENTO: A ablação por cateter é uma terapia bem estabelecida para controle do ritmo cardíaco em pacientes refratários ou intolerantes a drogas antiarrítmicas (DAA). Porém, a eficácia desse procedimento comparada à de DAA como estratégia de primeira linha no controle do ritmo cardíaco na fibrilação atrial é menos conhecida. OBJETIVOS: Conduzir uma revisão sistemática e metanálise da ablação por cateter vs. DAA em pacientes sem nenhum tratamento prévio para controle do ritmo. MÉTODOS: Buscamos, nos bancos de dados do PubMed, EMBASE, e Cochrane, ensaios randomizados controlados que compararam ablação por cateter com DAA para controle do ritmo cardíaco em pacientes com FA sintomática e descreveram os seguintes desfechos: (1) recorrência de taquiarritmia atrial (TA); (2) FA sintomática; (3) internações hospitalares; e (4) bradicardia sintomática. A heterogeneidade foi avaliada por estatística I2. Valores de p menores que 0,05 foram considerados estatisticamente significativos. RESULTADOS: Incluímos cinco ensaios com 994 pacientes, dos quais 502 (50,5%) foram submetidos à ablação por cateter. O período médio de acompanhamento foi de um a cinco anos. Recorrências de TA (OR 0,36; IC95% 0,25-0,52; p<0,001) e de FA sintomática (OR 0,32; IC95% 0,18-0,57; p<0,001), e internações hospitalares (OR 0,25; IC95% 0,15-0,42; p<0,001) foram menos frequentes nos pacientes tratados com ablação por cateter que naqueles tratados com DAA. Bradicardia sintomática não foi diferente entre os grupos (OR 0,55; IC95% 0,18-1,65; p=0,28). Derrame ou tamponamento pericárdico significativo ocorreu em oito dos 464 (1,7%) pacientes no grupo submetido à ablação. CONCLUSÃO: Esses achados sugerem maior eficácia da ablação por cateter que das DAA como estratégia inicial de controle do ritmo cardíaco em pacientes com DA sintomática.
Subject(s)
Atrial Fibrillation , Catheter Ablation , Anti-Arrhythmia Agents/therapeutic use , Atrial Fibrillation/drug therapy , Atrial Fibrillation/surgery , Catheter Ablation/adverse effects , Heart Atria , Humans , Recurrence , Treatment OutcomeABSTRACT
Resumo Fundamento A ablação por cateter é uma terapia bem estabelecida para controle do ritmo cardíaco em pacientes refratários ou intolerantes a drogas antiarrítmicas (DAA). Porém, a eficácia desse procedimento comparada à de DAA como estratégia de primeira linha no controle do ritmo cardíaco na fibrilação atrial é menos conhecida. Objetivos Conduzir uma revisão sistemática e metanálise da ablação por cateter vs. DAA em pacientes sem nenhum tratamento prévio para controle do ritmo. Métodos Buscamos, nos bancos de dados do PubMed, EMBASE, e Cochrane, ensaios randomizados controlados que compararam ablação por cateter com DAA para controle do ritmo cardíaco em pacientes com FA sintomática e descreveram os seguintes desfechos: (1) recorrência de taquiarritmia atrial (TA); (2) FA sintomática; (3) internações hospitalares; e (4) bradicardia sintomática. A heterogeneidade foi avaliada por estatística I2. Valores de p menores que 0,05 foram considerados estatisticamente significativos. Resultados Incluímos cinco ensaios com 994 pacientes, dos quais 502 (50,5%) foram submetidos à ablação por cateter. O período médio de acompanhamento foi de um a cinco anos. Recorrências de TA (OR 0,36; IC95% 0,25-0,52; p<0,001) e de FA sintomática (OR 0,32; IC95% 0,18-0,57; p<0,001), e internações hospitalares (OR 0,25; IC95% 0,15-0,42; p<0,001) foram menos frequentes nos pacientes tratados com ablação por cateter que naqueles tratados com DAA. Bradicardia sintomática não foi diferente entre os grupos (OR 0,55; IC95% 0,18-1,65; p=0,28). Derrame ou tamponamento pericárdico significativo ocorreu em oito dos 464 (1,7%) pacientes no grupo submetido à ablação. Conclusão Esses achados sugerem maior eficácia da ablação por cateter que das DAA como estratégia inicial de controle do ritmo cardíaco em pacientes com DA sintomática.
Abstract Background Catheter ablation is a well-established therapy for rhythm control in patients who are refractory or intolerant to anti-arrhythmic drugs (AAD). Less is known about the efficacy of catheter ablation compared with AAD as a first-line strategy for rhythm control in atrial fibrillation (AF). Objectives We aimed to perform a systematic review and meta-analysis of catheter ablation vs. AAD in patients naïve to prior rhythm control therapies. Methods PubMed, EMBASE, and Cochrane databases were searched for randomized controlled trials that compared catheter ablation to AAD for initial rhythm control in symptomatic AF and reported the outcomes of (1) recurrent atrial tachyarrhythmias (ATs); (2) symptomatic AF; (3) hospitalizations; and (4) symptomatic bradycardia. Heterogeneity was examined with I2statistics. P values of < 0.05 were considered statistically significant. Results We included five trials with 994 patients, of whom 502 (50.5%) underwent catheter ablation. Mean follow-up ranged from one to five years. Recurrences of AT (OR 0.36; 95% CI 0.25-0.52; p<0.001) and symptomatic AF (OR 0.32; 95% CI 0.18-0.57; p<0.001), and hospitalizations (OR 0.25; 95% CI 0.15-0.42; p<0.001) were significantly less frequent in patients treated with catheter ablation compared with AAD. Symptomatic bradycardia was not significantly different between groups (OR 0.55; 95% CI 0.18-1.65; p=0.28). Significant pericardial effusions or tamponade occurred in eight of 464 (1.7%) patients in the catheter ablation group. Conclusion These findings suggest that catheter ablation has superior efficacy to AAD as an initial rhythm control strategy in patients with symptomatic AF.
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BACKGROUND AND AIMS: There are limited data on serial coronary artery calcium (CAC) assessments outside North American and European populations. We sought to investigate risk factors for CAC incidence and progression in the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil). METHODS: We included individuals with no prior cardiovascular disease and two CAC measurements in ELSA-Brasil. Incident CAC was defined as a baseline CAC of 0 followed by CAC >0 on the second study. CAC progression was defined according to multiple published criteria. We performed logistic and linear regression to identify risk factors for CAC incidence and progression. We also examined risk factor effect modification by baseline CAC (0 vs. >0). RESULTS: A total of 2707 individuals were included (57% women, age 48.6 ± 7.7 years). Participants self-identified as white (55%), brown (24%), black (16%), Asian (4%) and Indigenous (1%). The mean period between CAC assessments was 5.1 ± 0.9 years. CAC incidence occurred in 282 (13.3%) of 2127 individuals with baseline CAC of 0. CAC progression occurred in 319 (55%) of 580 participants with baseline CAC >0. Risk factors for CAC incidence included older age, male sex, white race, hypertension, diabetes, higher BMI, smoking, lower HDL-C, higher LDL-C and triglycerides, and metabolic syndrome. Older age and elevated LDL-C were associated with CAC incidence, but not progression. Risk factors consistently associated with CAC progression were hypertension, diabetes, hypertriglyceridemia, and metabolic syndrome. On interaction testing, these four risk factors were more strongly associated with CAC progression as compared to CAC incidence. CONCLUSIONS: CAC incidence was associated with multiple traditional risk factors, whereas the only risk factors associated with progression of CAC were hypertension, diabetes, hypertriglyceridemia, and metabolic syndrome.
Subject(s)
Coronary Artery Disease , Vascular Calcification , Adult , Aged , Brazil/epidemiology , Calcium , Coronary Artery Disease/diagnostic imaging , Coronary Artery Disease/epidemiology , Disease Progression , Female , Humans , Incidence , Longitudinal Studies , Male , Middle Aged , Risk Factors , Vascular Calcification/diagnostic imaging , Vascular Calcification/epidemiologyABSTRACT
Regulatory T (Treg) cells may play an important role in the pathogenesis of paracoccidioidomycosis (PCM), but data on the role of Treg cells in the context of oral PCM are still scarce. The objectives of this study were to investigate the density of FoxP3(+) T regulatory cells in oral PCM and to correlate the results with the density of Paracoccidioides brasiliensis in the lesions. Cases of chronic oral PCM seen between 2000 and 2008 were included in this study. The diagnosis of all lesions was confirmed with histopathological examination and Grocott-Gomori staining. The quantitative analysis of the viable fungi was conducted in all cases with Grocott-stained slides. Treg cells were identified using antibodies against FoxP3. Pearson correlation coefficient was used to test the correlation between the density of fungi and Treg cells. Results were considered significant when P < 0.05. A total of 11 cases of oral PCM were obtained. There was a positive correlation between fungal density and FoxP3(+) Treg cells density in oral lesions, however, without statistical significance. A positive relation between Treg cells and fungal density was seen in oral PCM. Further studies are required to further elucidate the role of these cells in the pathogenesis of oral PCM, as well the clinical significance of these findings.
Subject(s)
Forkhead Transcription Factors/analysis , Mouth Diseases/immunology , Mouth Diseases/microbiology , Paracoccidioides/isolation & purification , Paracoccidioidomycosis/immunology , Paracoccidioidomycosis/microbiology , T-Lymphocytes, Regulatory/immunology , Adult , Aged , Colony Count, Microbial , Cross-Sectional Studies , Female , Humans , Lymphocyte Count , Male , Middle Aged , Statistics as Topic , T-Lymphocytes, Regulatory/chemistryABSTRACT
Ameloblastomas are odontogenic tumors that are locally invasive and slow-growing. Their etiology is still not well defined, but the forms of treatment have been widely discussed because of the possibility of tumor recurrence and postoperative complications. In this study, six patients who were diagnosed with ameloblastoma in the mandibular region and were treated in the Department of Orthopedics and Traumatology of Hospital das Clínicas, Federal University of Goiás, between 1958 and 1963, were evaluated. The radiological, clinical and therapeutic characteristics were evaluated. There was no predominance regarding gender in the sample studied. The symptoms most often presented by the patients were pain and tumor formation. The radiological characteristics with greatest incidence were multilocular lesions and the treatment used for all the patients was radical surgery. There was no recurrence over the minimum follow-up period of one year and six months...
Os ameloblastomas são tumores odontogênicos, localmente invasivos e de crescimento lento. Sua etiologia ainda não foi bem definida e as formas de tratamento são amplamente discutidas, por causa de possíveis recidivas do tumor e complicações pós-operatórias. Neste trabalho, foram avaliados seis pacientes diagnosticados com ameloblastoma na região mandibular e tratados no Departamento de Ortopedia e Traumatologia do HC-UFG, de 1958 a 1963. Foram avaliadas as características radiológicas, clínicas e terapêuticas. Não houve predomínio em relação ao gênero na amostra estudada. Os sintomas mais apresentados pelos pacientes foram dor e tumoração. As características radiológicas de maior incidência são de uma lesão multilocular e o tratamento usado em todos os pacientes foi o cirúrgico radical. A recidiva foi nula em um tempo mínimo de um ano e sete meses de seguimento...