Daniel Ferrante

Omega-3 Fatty Acids for the Prevention of Recurrent Symptomatic Atrial Fibrillation: Results of the FORWARD (Randomized Trial to Assess Efficacy of PUFA for the Maintenance of Sinus Rhythm in Persistent Atrial Fibrillation) Trial

OBJECTIVES The aim of this study was to evaluate the efficacy of polyunsaturated fatty acids (n-3 PUFA) for the prevention of recurrent atrial fibrillation (AF) in patients with normal sinus rhythm. BACKGROUND Current pharmacological treatments to limit recurrent AF in patients with previous AF have limited efficacy and high rates of adverse events. Results of trials that tested the efficacy of n-3 PUFA provided heterogeneous results. METHODS This was a prospective, randomized, double-blind, placebo-controlled, multicenter trial involving 586 outpatient participants with confirmed symptomatic paroxysmal AF that required cardioversion (n = 428), at least 2 episodes of AF in the 6 months before randomization (n = 55), or both (103). Patients were randomly allocated to n-3 PUFA (1 g/day) or placebo for 12 months. The primary endpoint was symptomatic recurrence of AF. RESULTS There were no significant differences between patients allocated to placebo and those who received n-3 PUFA for the main outcome. At 12 months, 56 of 297 participants (18.9%) in the placebo group and 69 of 289 participants (24.0%) in the n-3 PUFA group had a recurrent symptomatic AF (hazard ratio: 1.28, 95% confidence interval: 0.90 to 1.83, p = 0.17). There was no difference between treatment with placebo and n-3 PUFA for any of the other pre-specified endpoints, including the composite of all-cause mortality, nonfatal stroke, nonfatal acute myocardial infarction, systemic embolism, heart failure development, or severe bleeding that occurred in 20 (6.7%) and 16 (5.5%) of patients randomized to placebo or n-3 PUFA, respectively (hazard ratio: 0.86, 95% confidence interval: 0.44 to 1.66, p = 0.65). CONCLUSIONS Pharmacological supplementation with 1 g of n-3 PUFA for 1 year did not reduce recurrent AF. (Randomized Trial to Assess Efficacy of PUFA for the Maintenance of Sinus Rhythm in Persistent Atrial Fibrillation [FORWARD]; NCT00597220).

N-3 Polyunsaturated Fatty Acids to Prevent Atrial Fibrillation: Updated Systematic Review and Meta-Analysis of Randomized Controlled Trials

Background Previous studies have suggested that n‐3 polyunsaturated fatty acids (n‐3 PUFAs) have antiarrhythmic effects on atrial fibrillation (AF). We aimed to assess the effects of therapy with n‐3 PUFAs on the incidence of recurrent AF and on postoperative AF. Methods and Results Electronic searches were conducted in Web of Science, Medline, Biological Abstracts, Journal Citation Reports, and the Cochrane Central Register of Controlled Trials databases. In addition, data from the recently completed FORωARD and OPERA trials were included. We included randomized controlled trials comparing treatment with n‐3 PUFAs versus control to (1) prevent recurrent AF in patients who underwent reversion of AF or (2) prevent incident postoperative AF after cardiac surgery. Of identified studies, 12.9% (16 of 124) were included, providing data on 4677 patients. Eight studies (1990 patients) evaluated n‐3 PUFA effects on AF recurrence among patients with reverted AF and 8 trials (2687 patients) on postoperative AF. Pooled risk ratios through random‐effects models showed no significant effects on AF recurrence (RR, 0.95; 95% CI, 0.79 to 1.13; I2, 72%) or on postoperative AF (0.86; 95% CI, 0.71 to 1.04; I2, 53.1%). A funnel plot suggested publication bias among postoperative trials but not among persistent AF trials. Meta‐regression analysis did not find any relationship between doses and effects (P=0.887 and 0.833 for recurrent and postoperative AF, respectively). Conclusions Published clinical trials do not support n‐3 PUFAs as agents aimed at preventing either postoperative or recurrent AF. Clinical Trial Registration URL: http://www.crd.york.ac.uk/PROSPERO. Unique Identifier: CRD42012002199.

Clinical ResearchHeart Rhythm Disorders in Heart FailureOmega-3 Fatty Acids for the Prevention of Recurrent Symptomatic Atrial Fibrillation: Results of the FORWARD (Randomized Trial to Assess Efficacy of PUFA for the Maintenance of Sinus Rhythm in Persistent Atrial Fibrillation) Trial

OBJECTIVES The aim of this study was to evaluate the efficacy of polyunsaturated fatty acids (n-3 PUFA) for the prevention of recurrent atrial fibrillation (AF) in patients with normal sinus rhythm. BACKGROUND Current pharmacological treatments to limit recurrent AF in patients with previous AF have limited efficacy and high rates of adverse events. Results of trials that tested the efficacy of n-3 PUFA provided heterogeneous results. METHODS This was a prospective, randomized, double-blind, placebo-controlled, multicenter trial involving 586 outpatient participants with confirmed symptomatic paroxysmal AF that required cardioversion (n = 428), at least 2 episodes of AF in the 6 months before randomization (n = 55), or both (103). Patients were randomly allocated to n-3 PUFA (1 g/day) or placebo for 12 months. The primary endpoint was symptomatic recurrence of AF. RESULTS There were no significant differences between patients allocated to placebo and those who received n-3 PUFA for the main outcome. At 12 months, 56 of 297 participants (18.9%) in the placebo group and 69 of 289 participants (24.0%) in the n-3 PUFA group had a recurrent symptomatic AF (hazard ratio: 1.28, 95% confidence interval: 0.90 to 1.83, p = 0.17). There was no difference between treatment with placebo and n-3 PUFA for any of the other pre-specified endpoints, including the composite of all-cause mortality, nonfatal stroke, nonfatal acute myocardial infarction, systemic embolism, heart failure development, or severe bleeding that occurred in 20 (6.7%) and 16 (5.5%) of patients randomized to placebo or n-3 PUFA, respectively (hazard ratio: 0.86, 95% confidence interval: 0.44 to 1.66, p = 0.65). CONCLUSIONS Pharmacological supplementation with 1 g of n-3 PUFA for 1 year did not reduce recurrent AF. (Randomized Trial to Assess Efficacy of PUFA for the Maintenance of Sinus Rhythm in Persistent Atrial Fibrillation [FORWARD]; NCT00597220).

Omega-3 fatty acid supplementation reduces one-year risk of atrial fibrillation in patients hospitalized with myocardial infarction

PurposeCurrent strategies for avoiding atrial fibrillation (AF) are of limited value. We aim to assess the relationship between omega-3 fatty acids (n-3 PUFA) and AF occurrence in post-myocardial infarction (MI) patients.MethodsA population study, linking hospital discharge records, prescription databases, and vital statistics, was conducted and included all consecutive patients with MI (ICD-9: 410) in six Italian local health authorities over a 3-year period. A propensity score (PS)-based, 5-to-1, greedy 1:1 matching algorithm was used to check consistency of results. Sensitivity analysis was performed to assess the robustness of findings.ResultsN-3 PUFA reduced the relative risk of the hospitalization for AF [hazard ratio (HR) 0.19, 95% CI 0.07–0.51] and was associated with a further and complementary reduction in all-cause mortality (HR 0.15, 95% CI 0.05–0.46). PS-based matched analysis and sensitivity analysis confirmed the main results.Conclusionn-3 PUFA reduced both all-cause mortality and incidence of 1-year AF in patients hospitalized with MI.

Reduction in hospital admissions for acute coronary syndrome after the successful implementation of 100% smoke-free legislation in Argentina: a comparison with partial smoking restrictions

Background Several studies have shown a decrease in acute coronary syndrome (ACS) admissions after the implementation of 100% smoke-free legislation. However, no studies have been conducted in developing countries. Methods We conducted a time series analysis of ACS hospital admissions in Santa Fe province and Buenos Aires city, Argentina. In 2006, Santa Fe implemented a 100% smoke-free law and Buenos Aires implemented a partial law with designated smoking areas and exceptions. Age-standardised ACS admissions rates were compared before and after the implementation of the laws in each district. Smoking prevalence, compliance with legislation and exposure to secondhand smoke (SHS) was also assessed in both districts. Results In Santa Fe an immediate decrease in ACS admissions was observed after implementation (−2.5 admissions per 100 000, p=0.03; 13% reduction), compared with no change in Buenos Aires city (rate ratio Santa Fe vs Buenos Aires: 0.74, 95% CI 0.63 to 0.86, p≤0.001). In Santa Fe, the immediate effect was followed by a persistent decrease in admissions due to ACS (−0.26 admissions per 100 000 per month). Smoking prevalence did not change significantly in either district during the same period. In both districts, there was a reduction in self-reported SHS exposure, with a trend towards lower exposure in Santa Fe province. No other comprehensive tobacco control interventions were implemented during the study period. Conclusions A 100% smoke-free law was more effective than a partial restriction law in reducing ACS admissions. An immediate effect was followed by a sustained decrease in ACS admissions. Smoke-free initiatives can be also effective in decreasing acute coronary events in developing countries.

The rationale and design of the FORωARD Trial: A randomized, double-blind, placebo-controlled, independent study to test the efficacy of n-3 PUFA for the maintenance of normal sinus rhythm in patients with previous atrial fibrillation

BACKGROUND Atrial fibrillation (AF) is associated with increased risk of death, thromboembolic complications, and a lowered quality of life. Despite this burden, pharmacologic agents for prevention of AF in patients who achieved normal sinus rhythm are of limited utility, mostly because of serious and frequent side effects. Thus, the availability of safer and more effective drugs may reduce the burden of disease. TRIAL DESIGN Patients aged > or =21 years with previous symptomatic AF and who have recovered normal sinus rhythm will be randomized to 1 g daily of omega-3-acid ethyl esters or identical placebo. To be included in the trial, patients must have either (a) at least 2 symptomatic episodes of documented AF in the 6 months before randomization, with the last episode occurring in the 14 to 90 days before randomization (paroxysmal AF), or (b) successful electrical or pharmacologic cardioversion for persistent AF. Ethical committees of 71 cardiology centers in 16 provinces of Argentina have qualified and approved the protocol and are expected to enroll 1,400 patients to test the primary end point of efficacy, which is survival free of AF during follow-up. CONCLUSION The Fish Oil Reserach with omega-3 for Atrial fibrillation Recurrence Delay (FORomegaARD) trial will determine whether pharmacologic supplementation with 1 g of omega-3-acid ethyl esters can reduce AF recurrence in patients with previous AF who have recovered normal sinus rhythm.

Socioeconomic Status and Tobacco Consumption Among Adolescents: A Multilevel Analysis of Argentina’s Global Youth Tobacco Survey

INTRODUCTION The relationship between poverty and tobacco consumption among adolescents has not been extensively studied, and what evidence exists has come almost entirely from developed countries. Moreover, the impact of contextual factors--such as school-level poverty--remains unclear. METHODS We obtained information about smoking behavior from the Global Youth Tobacco Survey in Argentina in 2007. School-level characteristics were derived by matching schools to census areas from the 2001 Census. Additional school-level information was obtained from the Ministry of Education. Random intercept models were used to evaluate the associations of school-level variables (poverty in the census area of the school, school receipt of social assistance, and public or private status) with current smoking, intention to quit, secondhand smoke exposure outside the home, support for smoke-free laws, purchase of single cigarettes among smokers, and susceptibility to smoking in 5 years among nonsmokers. RESULTS After controlling for age and sex, students attending schools receiving social assistance were more likely to smoke (odds ratio [OR] 1.35, 95% CI 1.02-1.80) and to purchase loose cigarettes (OR 1.66, 95% CI 1.08-2.54), whereas school poverty was significantly associated with secondhand smoke exposure (OR 1.27, 95% CI 1.04-1.58). CONCLUSION This study shows that an association exists between unfavorable contextual school characteristics and tobacco consumption and related measures among youth in Argentina. Efforts to prevent smoking may need to address the school-level factors that place youth at higher risk.

Impact on cardiovascular disease events of the implementation of Argentina's national tobacco control law

Background Argentinas congress passed a tobacco control law that would enforce 100% smoke-free environments for the entire country, strong and pictorial health warnings on tobacco products and a comprehensive advertising ban. However, the Executive Branch continues to review the law and it has not been fully implemented. Our objective was to project the potential impact of full implementation of this tobacco control legislation on cardiovascular disease. Methods The Coronary Heart Disease (CHD) Policy Model was used to project future cardiovascular events. Data sources for the model included vital statistics, morbidity and mortality data, and tobacco use estimates from the National Risk Factor Survey. Estimated effectiveness of interventions was based on a literature review. Results were expressed as life-years, myocardial infarctions and strokes saved in an 8-year-period between 2012 and 2020. In addition we projected the incremental effectiveness on the same outcomes of a tobacco price increase not included in the law. Results In the period 2012–2020, 7500 CHD deaths, 16 900 myocardial infarctions and 4300 strokes could be avoided with the full implementation and enforcement of this law. Annual per cent reduction would be 3% for CHD deaths, 3% for myocardial infarctions and 1% for stroke. If a tobacco price increase is implemented the projected avoided CHD deaths, myocardial infarctions and strokes would be 15 500, 34 600 and 11 900, respectively. Conclusions Implementation of the tobacco control law would produce significant public health benefits in Argentina. Strong advocacy is needed at national and international levels to get this law implemented throughout Argentina.

Relación costo-utilidad de la disminución del consumo de sal y su efecto en la incidencia de enfermedades cardiovasculares en Argentina

OBJETIVO: Estimar la relacion costo-utilidad de una intervencion dirigida a reducir el consumo de sal en la dieta de personas mayores de 35 anos en Argentina. METODOS: La intervencion consistio en reducir entre 5% y 25% el contenido de sal en los alimentos. Se utilizo el modelo de simulacion del impacto de las politicas sobre la enfermedad coronaria para predecir la evolucion de la incidencia, la prevalencia, la mortalidad y los costos en la poblacion de la enfermedad coronaria y cerebrovascular en personas de 35 a 84 anos. Se modelo el efecto y los costos de una disminucion de 3 g de sal en la dieta, mediante su reduccion en alimentos procesados y en la anadida por los consumidores, por un periodo de 10 anos. Se estimo el cambio en la ocurrencia de eventos en este periodo y la ganancia en anos de vida ajustados por la calidad (AVAC) en un escenario de efecto alto y otro de efecto bajo. RESULTADOS: La intervencion genero un ahorro neto de US

Telephone interventions for disease management in heart failure

3 765 millones y una ganancia de 656 657 AVAC en el escenario de efecto alto y de US