Lipoprotein(a) as a cardiovascular risk factor among patients with and without diabetes Mellitus: the Mass General Brigham Lp(a) Registry.

BACKGROUND: Diabetes mellitus (DM) and Lp(a) are well-established predictors of coronary artery disease (CAD) outcomes. However, their combined association remains poorly understood. OBJECTIVE: To investigate the relationship between elevated Lp(a) and DM with CAD outcomes. METHODS: Retrospective analysis of the MGB Lp(a) Registry involving patients ≥ 18 years who underwent Lp(a) measurements between 2000 and 2019. Exclusion criteria were severe kidney dysfunction, malignant neoplasms, and prior atherosclerotic cardiovascular disease (ASCVD). The primary outcome was a combination of cardiovascular death or myocardial infarction (MI). Elevated Lp(a) was defined as > 90th percentile (≥ 216 nmol/L). RESULTS: Among 6,238 patients who met the eligibility criteria, the median age was 54, 45% were women, and 12% had DM. Patients with DM were older, more frequently male, and had a higher prevalence of additional cardiovascular risk factors. Over a median follow-up of 12.9 years, patients with either DM or elevated Lp(a) experienced higher rates of the primary outcome. Notably, those with elevated Lp(a) had a higher incidence of the primary outcome regardless of their DM status. The annual event rates were as follows: No-DM and Lp(a) < 90th% - 0.6%; No-DM and Lp(a) > 90th% - 1.3%; DM and Lp(a) < 90th% - 1.9%; DM and Lp(a) > 90th% - 4.7% (p < 0.001). After adjusting for confounders, elevated Lp(a) remained independently associated with the primary outcome among both patients with DM (HR = 2.66 [95%CI: 1.55-4.58], p < 0.001) and those without DM (HR = 2.01 [95%CI: 1.48-2.74], p < 0.001). CONCLUSIONS: Elevated Lp(a) constitutes an independent and incremental risk factor for CAD outcomes in patients with and without DM.

Anticoagulação Crônica em Pacientes com Fibrilação Atrial e COVID-19: Uma Revisão Sistemática e Metanálise / Chronic Anticoagulation in Patients with Atrial Fibrillation and COVID-19: A Systematic Review and Meta-Analysis

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.

The association of lipoprotein(a) and coronary artery calcium in asymptomatic patients: a systematic review and meta-analysis.

AIMS: Lipoprotein(a) [Lp(a)] is an atherogenic lipid particle associated with increased risk for coronary heart disease (CHD) events. Coronary artery calcium (CAC) score is a tool to diagnose subclinical atherosclerosis and guide clinical decision-making for primary prevention of CHD. Studies show conflicting results concerning the relationship between Lp(a) and CAC in asymptomatic populations. We conducted a meta-analysis to evaluate the association of Lp(a) and CAC in asymptomatic patients. METHODS AND RESULTS: We systematically searched PubMed, Embase, and Cochrane until April 2023 for studies evaluating the association between Lp(a) and CAC in asymptomatic patients. We evaluated CAC > 0 Agatston units, and CAC ≥ 100. Lp(a) was analysed as a continuous or dichotomous variable. We assessed the association between Lp(a) and CAC with pooled odds ratios (OR) adopting a random-effects model. A total of 23 105 patients from 18 studies were included in the meta-analysis with a mean age of 55.9 years, 46.4% female. Elevated Lp(a) increased the odds of CAC > 0 [OR 1.31; 95% confidence intervals (CI) 1.05-1.64; P = 0.02], CAC ≥100 (OR 1.29; 95% CI 1.01-1.65; P = 0.04; ), and CAC progression (OR 1.43; 95% CI 1.20-1.70; P < 0.01; ). For each increment of 1 mg/dL in Lp(a) there was a 1% in the odds of CAC > 0 (OR 1.01; 95% CI 1.01-1.01; P < 0.01). CONCLUSION: Our findings of this meta-analysis suggest that Lp(a) is positively associated with a higher likelihood of CAC. Higher Lp(a) levels increased the odds of CAC >0. These data support the concept that Lp(a) is atherogenic, although with high heterogeneity and a low level of certainty. PROTOCOL REGISTRATION: CRD42023422034. KEY FINDINGS: Asymptomatic patients with elevated Lp(a) had 31% higher chances of having any coronary calcification (CAC > 0) and 29% higher chances of having more advanced calcification (CAC > 100). It increased the chances of having progression of coronary calcification over time by 43%. For each 1 mg/dL of Lp(a) there was an increment of 1% chance of having coronary calcification.

We conducted a meta-analysis to evaluate the association between Lp(a) and coronary calcification in asymptomatic patients without a known history of coronary artery disease.

Early Initiation of PCSK9 Inhibitor Therapy Versus Placebo in Patients With Acute Coronary Syndrome: A Systematic Review and Meta-Analysis.

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, p = 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.

Angiotensin Receptor-Neprilysin Inhibitor Effects on Atherosclerotic Cardiovascular Disease Events: A Meta-Analysis of Randomized Controlled Trials.

Sacubitril-valsartan is an angiotensin receptor-neprilysin inhibitor (ARNI) associated with a decreased risk of death and hospitalization for selected patients with heart failure (HF). However, its association with improved atherosclerotic cardiovascular disease (ASCVD) events remains unclear. We performed a meta-analysis to evaluate the association of ARNI with ASCVD events in patients with HF. We systematically searched PubMed, Embase, Cochrane, and ClinicalTrials.gov for studies comparing ARNIs with angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin receptor blockers (ARBs) in terms of myocardial infarction, stroke, angina pectoris, peripheral artery disease, and the composite end point in patients with HF. A total of 8 randomized controlled trials were included, with 17,541 patients assigned to either the ARNI (8,764 patients) or ACEi/ARB (8,777 patients) groups. The incidence of composite end point (risk ratio [RR] 1.03, 95% confidence interval [CI] 0.93 to 1.13, p = 0.63), myocardial infarction (RR 1.02, 95% CI 0.81 to 1.30, p = 0.85), angina pectoris (RR 0.96, 95% CI 0.80 to 1.17, p = 0.70), and stroke (RR 0.99, 95% CI 0.85 to 1.16, p = 0.93) were not statistically different between the ARNI and ACEi/ARB groups. However, ARNI was associated with a higher incidence of peripheral artery disease (RR 1.63, 95% CI 1.05 to 2.52, p = 0.03). In conclusion, this meta-analysis found no association between ARNI therapy and improved ASCVD events in patients with HF.

Efficacy and safety of the dual GIP and GLP-1 receptor agonist tirzepatide for weight loss: a meta-analysis of randomized controlled trials.

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.

Polypill-based strategy vs. usual care for secondary prevention of cardiovascular disease: a meta-analysis of randomized controlled trials.

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.

Pretreatment with P2Y12 inhibitors in ST-elevation myocardial infarction: A systematic review and meta-analysis.

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.

Long-term outcomes of percutaneous versus surgical revascularization in patients with diabetes and left main coronary artery disease: A meta-analysis of randomized controlled trials.

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.

Transcatheter Aortic Valve Replacement for Severe Symptomatic Aortic Stenosis in Rheumatic Heart Disease: A Systematic Review.

Transcatheter aortic valve replacement (TAVR) is well-established for severe symptomatic aortic stenosis (AS), but its use in rheumatic heart disease (RHD) has been limited. We systematically review the use of TAVR for severe symptomatic AS in RHD. Pubmed, Embase, and Scopus were searched for TAVR for symptomatic severe AS and proven or suspected RHD. Procedure characteristics, efficacy, and safety endpoints were collected and all definitions were based on the Valve Academic Research Consortium-2 (VARC-2) criteria. We included 3 case series and 12 case reports, with a total of 43 patients. Mean age was 76 years, 75% were female, and 85% had NYHA class III-IV symptoms. Follow up ranged from 1 to 29 months. Patients were moderate to high risk, with Society of Thoracic Surgery score ranging from 6.1% to 17.6%. The approach was transfemoral in 30 (83%) cases. Procedural success occurred in 37 (86%) patients. Of the 7 patients with periprocedural complications, 4 had valve dislodgement, 1 deployment failure, 1 unplanned cardiopulmonary bypass, and 1 moderate aortic regurgitation. Paravalvular leak was reported in 5 (11.6%) patients. Only 1 patient had heart block requiring pacemaker. Among 13 studies (23 patients), 30-day mortality was 0%. One case series with 19 patients had a 30-day, 1-year, 2-year, and 5-year mortality of 5%, 11%, 31%, and 48%, respectively. TAVR appears feasible for selected patients with rheumatic severe AS, albeit our results indicate a 14% incidence of device failure. Future randomized clinical trials may clarify the role of TAVR in this group.

Extra-coronary Calcification and Cardiovascular Events: What Do We Know and Where Are We Heading?

PURPOSE OF REVIEW: The coronary artery calcium score is a guideline-endorsed aid for further risk stratification in the primary prevention of atherosclerotic cardiovascular disease. The non-contrast scan performed for detection of coronary artery calcium also gives an opportunity to visualize calcifications in the thoracic aorta and in the heart valves, at no additional cost or radiation exposure. The purpose of this review was to discuss the potential clinical value of measuring thoracic aortic calcification, aortic valve calcification, and mitral annulus calcification. RECENT FINDINGS: After two decades of active research, all three calcifications have been extensively evaluated, across various cohorts. We discuss classic and recent studies, current knowledge gaps, and future directions in this space. The added value of these measurements has traditionally been considered modest at best, and they are not currently discussed in relevant primary prevention guidelines in North America and Europe. However, recent studies evaluating high thoracic calcification thresholds and younger populations have further enriched this space. Specifically, some studies suggest that detection of severe thoracic aortic calcification may be helpful in further risk assessment and that detection of aortic valve calcifications may have important prognostic implications in younger individuals. Although more research is needed, particularly in larger young-to-middle-aged cohorts, future guidelines might consider including these features as risk-enhancing factors.

Ablação por Cateter é Superior a Drogas Antiarrítmicas como Tratamento de primeira linha para Fibrilação Atrial: uma Revisão Sistemática e Metanálise / Catheter Ablation is Superior to Antiarrhythmic Drugs as First-Line Treatment for Atrial Fibrillation: a Systematic Review and Meta-Analysis

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.

Risk Markers for Limited Coronary Artery Calcium in Persons With Significant Aortic Valve Calcium (From the Multi-ethnic Study of Atherosclerosis).

The early stages of aortic valve calcification (AVC) and coronary artery calcification (CAC) include shared ASCVD risk factors, yet there is considerable heterogeneity between the burden of AVC, and CAC. We sought to identify the markers associated with limited CAC among persons with significant AVC. There were 325 participants from the Multi-Ethnic Study of Atherosclerosis without clinical ASCVD and with AVC ≥100 Agatston units (AU) at Visit 1. Multivariable-adjusted prevalence ratios for limited CAC (0 to 99 AU) were calculated using modified Poisson regression. Participants had a mean age of 72.1 years, median AVC score of 209, and 34% were women. A total of 133 (41%) participants had CAC <100, of whom 46/133 had CAC = 0. Younger age (PR = 1.40, 95% CI: 1.22 to 1.62, per 10-years), female gender (PR = 1.68, 95% CI: 1.28 to 2.20), and low 10-year ASCVD risk (PR = 2.30, 95% CI: 1.85 to 2.85) were most strongly associated with limited CAC. Neither a normal lipoprotein(a) nor normal measures of inflammation were significantly associated with limited CAC. Lower serum phosphate (PR = 1.15, 95% CI: 1.01 to 1.31; per 0.5 mg/dl lower) and calcium-phosphate product (PR = 1.16, 95% CI: 1.02 to 1.34; per SD lower) were associated with an approximately 15% higher prevalence of limited CAC. In conclusion, more than 40% of persons with significant AVC had CAC. Beyond traditional risk factors, lower serum phosphate, and lower calcium-phosphate product were associated with a higher prevalence of limited CAC.

Meta-Analysis of Duration of Dual Antiplatelet Therapy in Acute Coronary Syndrome Treated With Coronary Stenting.

We aimed to evaluate if a shorter course of DAPT followed by P2Y12 inhibitor monotherapy is as effective as a 12-month course with fewer bleeding events. PubMed, Scopus, and Cochrane Central were searched for randomized controlled trials of ACS patients comparing dual antiplatelet therapy (DAPT) for 1 to 3 months followed by a P2Y12 inhibitor to 12-month DAPT. Quality assessment was performed with the Cochrane Collaboration risk of bias assessment tool. Five randomized clinical trials were included, with a total of 18,046 participants. Antiplatelet strategies were aspirin and P2Y12 inhibitor for 12 months compared with aspirin and P2Y12 inhibitor for 1 to 3 months followed by P212 inhibitor alone. Patients randomized to 1 to 3 months of DAPT followed by P2Y12 inhibitor monotherapy had lower rates of major bleeding (1.42% vs 2.53%; OR 0.53; 95% CI 0.42-0.67; p < 0.001; I2 = 0%) and all-cause mortality (1.00% vs 1.42%; OR 0.71; 95% CI 0.53-0.95; p = 0.02; I2=0%) with similar major adverse cardiac events (MACE) (2.66% vs 3.11%; OR 0.86; 95% CI 0.71 - 1.03; p = 0.10; I2 = 0 %) compared to 12 months of DAPT. In conclusion, shorter course of DAPT for 1 to 3 months followed by P2Y12 inhibitor monotherapy reduces major bleeding and all course mortality without increasing major adverse cardiac events compared with traditional DAPT for 12 months.

The role of Lipoprotein(a) in cardiovascular disease: Current concepts and future perspectives.

High lipoprotein(a) [Lp(a)] levels are associated with the development of atherosclerotic cardiovascular disease (ASCVD) and with calcific aortic valve stenosis (CAVS) both observationally and causally from human genetic studies. The mechanisms are not well characterized but likely involve its role as a carrier of oxidized phospholipids (OxPLs), which are known to be increased in pro-inflammatory states, to induce pro-inflammatory changes in monocytes leading to plaque instability, and to impair vascular endothelial cell function, a driver of acute and recurrent ischemic events. In addition, Lp(a) itself has prothrombotic activity. Current lipid-lowering strategies do not sufficiently lower Lp(a) serum levels. Lp(a)-specific-lowering drugs, targeting apolipoprotein(a) synthesis, lower Lp(a) by up to 90% and are being evaluated in ongoing clinical outcome trials. This review summarizes the current knowledge on the associations of Lp(a) with ASCVD and CAVS, the current role of Lp(a) assessment in the clinical setting, and emerging Lp(a)-specific-lowering therapies.

Predictors of coronary artery calcium incidence and progression: The Brazilian Longitudinal Study of Adult Health (ELSA-Brasil).

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.

Clinician's Guide to the Updated ABCs of Cardiovascular Disease Prevention: A Review Part 2.

Efforts to better control risk factors for cardiovascular disease and prevent the development of subsequent cardiovascular events are crucial to maintaining healthy populations. In today's busy practice environment and with the overwhelming pace of new research findings, ensuring appropriate emphasis and implementation of evidence-based preventive cardiovascular care can be challenging. The ABCDEF approach to cardiovascular disease prevention is intended to improve dissemination of contemporary best practices and ease the implementation of comprehensive preventive strategies for clinicians. This review serves as a succinct yet authoritative overview for interested internists as well as for cardiologists not otherwise focused on cardiovascular disease prevention. The goal of this 2-part series is to compile a state-of-the-art list of elements central to primary and secondary prevention of cardiovascular disease, using an ABCDEF checklist. In Part 2, we review new recommendations about lipid-modifying strategies, contemporary best practice for tobacco cessation, new evidence related to cardiovascular risk reduction in diabetes using novel therapies, ways to implement a heart-healthy diet, modern interventions to improve physical exercise, and how best to prevent the onset of heart failure.

Dual versus single antiplatelet therapy after coronary artery bypass graft surgery: An updated meta-analysis.

INTRODUCTION: The potential benefit and risks of dual antiplatelet therapy (DAPT) over single antiplatelet therapy (SAPT) in patients who undergo coronary artery bypass graft surgery (CABG) is controversial. METHODS: We performed a systematic review and meta-analysis of observational and randomized clinical trial (RCT) data comparing DAPT to SAPT following urgent or elective CABG. Subanalyses were performed restricted to: a) RCTs; b) stable ischemic heart disease (SIHD); c) extended duration DAPT (≥6 months); and d) follow-up ≥2 years. RESULTS: Twenty-two studies comprising 20,315 patients undergoing CABG were included. Of the participants studied, 7481 (37%) received postoperative DAPT and 12,834 (63%) received SAPT. Overall, DAPT was associated with a lower cardiovascular (CV) mortality (OR 0.67; p = 0.02) and a trend towards lower all-cause mortality (OR 0.78; p = 0.08). There were no differences in rates of myocardial infarction or stroke. Subanalyses in RCTs, SIHD, and prolonged follow-up failed to demonstrate improvement in these outcomes with DAPT. However, in studies with extended duration DAPT, stroke was significantly reduced in the DAPT group (OR 0.47; p = 0.04). Saphenous vein graft (SVG) occlusion up to 1 year after CABG was significantly lower with DAPT overall (OR 0.64; p < 0.01) and in the RCT subanalysis (OR 0.58; p < 0.01). Major bleeding was significantly higher with DAPT (OR 1.31; p = 0.03). CONCLUSION: While DAPT has been associated with lower CV mortality in observational samples undergoing CABG, such findings were not replicated in RCTs. Lower rates of SVG occlusion with DAPT are offset by a higher rate of major bleeding.