ABSTRACT
BACKGROUND: Takotsubo syndrome (TS) is a reversible cause of heart failure; however, a minority of patients can develop serious complications, including cardiac rupture (CR). OBJECTIVES: Analyze case reports of CR related to TS, detailing patient characteristics to uncover risk factors and prognosis for this severe complication. METHODS: We conducted a systematic search of MEDLINE and Embase databases to identify case reports of patients with TS complicated by CR, from inception to October 2023. RESULTS: We included 44 subjects (40 females; 4 males) with a median age of 75 (IQR 71-82) years, of White/Caucasian (61%) or East Asian/Japanese (39%) ethnicity. An emotional trigger was present in 15 (34%) subjects and an apical ballooning pattern was observed in all cases (100%). ST-segment elevation was reported in 39 (93%) of 42 cases, with the anterior myocardial segments (37 [88%]) being the most compromised, followed by lateral (26 [62%]) and inferior (14 [33%]) segments. The median time to cardiac rupture was 48 (5-120) hours since admission, with the left ventricular free wall (25 [57%]) being the most frequent site of perforation. Surgery was attempted in 16 (36%) cases, and 28 (64%) patients did not survive. CONCLUSIONS: CR related to TS is a rare complication associated with high mortality and affecting elderly females, specially from White/Caucasian or East Asian/Japanese descent, presenting with anterior or lateral ST-segment elevation, and an apical ballooning pattern. Although data is limited and additional prospective studies are needed, the awareness of this life-threatening complication is crucial to early identify high-risk patients. CONDENSED ABSTRACT: Cardiac rupture is a rare complication of Takotsubo syndrome. We conducted a systematic review of cases complicated by cardiac rupture, and we identified 44 subjects (40 females and 4 males) with a median age of 75 (IQR 71-82) years, of White/Caucasian (61%) or East Asian/Japanese (39%) ethnicity, all with an apical ballooning pattern (100%). The median time to cardiac rupture was 48 (5-120) hours since admission, with the left ventricular free wall (25 [57%]) being the most frequent site of perforation. Surgery treatment was attempted in 16 (36%) cases, and 28 (64%) patients did not survive.
Subject(s)
Heart Rupture , Takotsubo Cardiomyopathy , Humans , Takotsubo Cardiomyopathy/diagnosis , Takotsubo Cardiomyopathy/epidemiology , Takotsubo Cardiomyopathy/ethnology , Heart Rupture/etiology , Heart Rupture/diagnosis , Heart Rupture/epidemiology , Aged , Female , Male , Aged, 80 and overABSTRACT
BACKGROUND: Interleukin-1 blockade with anakinra reduces high-sensitivity C-reactive protein (hsCRP) levels and prevents heart failure (HF) events after ST-segment myocardial infarction (STEMI). Sex-based differences in STEMI patients have been reported, but no data are available regarding response to anakinra. METHODS: We analyzed the systemic inflammation and composite end-point of new-onset HF or death in women and men with STEMI treated with anakinra from three different Virginia Commonwealth University Anakinra Response Trial (VCUART) randomized clinical trials. RESULTS: We analyzed 139 patients, 29 (21%) were women while 110 (79%) were men. Baseline hsCRP was higher in women compared to men (8.9 [5.2-13.5] vs. 4.2 [2.1-7.7] mg/L, P<0.001). Eighty-four patients were treated with anakinra (22 [75%] women and 62 [56%] men). The area under the curve of hsCRP (hsCRP-AUC) after 14 days was numerically lower in patients receiving anakinra versus placebo both in men (86 [37-130] vs. 223 [119-374] mg day/L) and in women (73 [46-313] vs. 242 [102-988] mg day/L) (P<0.001 for multiple groups, P for interaction 0.22). The incidence of the composite endpoint was also numerically lower in the anakinra group compared to placebo, both in men (4 [6.4%] vs. 14 [29.1%]) and in women (3 [13.6%] vs. 2 [28.5%]) (P=0.019 for multiple groups, P for interaction 0.44). There were no statistically significant differences between women and men in hsCRP-AUC and death or HF events when comparing separately the anakinra and placebo groups (all P>0.05). CONCLUSIONS: Women were underrepresented in the VCUART trials, they appeared to have higher hsCRP levels at time of presentation, yet to benefit similar to men by treatment with anakinra in STEMI.
Subject(s)
Myocardial Infarction , ST Elevation Myocardial Infarction , Male , Humans , Female , Interleukin 1 Receptor Antagonist Protein/therapeutic use , ST Elevation Myocardial Infarction/drug therapy , Interleukin-1/therapeutic use , C-Reactive Protein/metabolism , C-Reactive Protein/therapeutic use , Treatment Outcome , Myocardial Infarction/drug therapyABSTRACT
Pre-clinical and clinical studies suggest a role for inflammation in the pathophysiology of cardiovascular (CV) diseases. The NLRP3 (NACHT, leucine-rich repeat, and pyrin domain-containing protein 3) inflammasome is activated during tissue injury and releases interleukin-1ß (IL-1ß). We describe three paradigms in which the NLRP3 inflammasome and IL-1ß contribute to CV diseases. During acute myocardial infarction (AMI), necrotic cell debris, including IL-1α, induce NLRP3 inflammasome activation and further damage the myocardium contributing to heart failure (HF) (acute injury paradigm). In chronic HF, IL-1ß is induced by persistent myocardial overload and injury, neurohumoral activation and systemic comorbidities favoring infiltration and activation of immune cells into the myocardium, microvascular inflammation, and a pro-fibrotic response (chronic inflammation paradigm). In recurrent pericarditis, an autoinflammatory response triggered by cell injury and maintained by the NLRP3 inflammasome/IL-1ß axis is present (autoinflammatory disease paradigm). Anakinra, recombinant IL-1 receptor antagonist, inhibits the acute inflammatory response in patients with ST elevation myocardial infarction (STEMI) and acute HF. Canakinumab, IL-1ß antibody, blunts systemic inflammation and prevents complications of atherosclerosis in stable patients with prior AMI. In chronic HF, anakinra reduces systemic inflammation and improves cardiorespiratory fitness. In recurrent pericarditis, anakinra and rilonacept, a soluble IL-1 receptor chimeric fusion protein blocking IL-1α and IL-1ß, treat and prevent acute flares. In conclusion, the NLRP3 inflammasome and IL-1 contribute to the pathophysiology of CV diseases, and IL-1 blockade is beneficial with different roles in the acute injury, chronic inflammation and autoinflammatory disease paradigms. Further research is needed to guide the optimal use of IL-1 blockers in clinical practice.
ABSTRACT
BACKGROUND: Atrial fibrillation is the most common arrhythmia worldwide and is associated with significant morbidity and mortality. Despite the effectiveness of catheter-based ablation, periprocedural complication and recurrences remain a concern. In this context, we aim to appraise the potential impact of brain-derived neurotrophic factor (BDNF) on reducing episodes of paroxysmal atrial fibrillation (PAF). METHODS: 22 patients with an established diagnosis of PAF and without structural heart disease were considered. Every patient received 20 drops of GUNA-BDNF administered in the morning. During the 24 months of follow-up, the arrhythmic burden was measured by the average monthly duration of PAF episodes. RESULTS: At the end of the follow-up period (24 months), data from 22 patients, of whom 17 men and five women, were analyzed. The arrhythmic burden, measured in terms of average monthly duration of PAF episodes, was found significantly reduced after the administration of low dose BDNF (9.5 vs. 65.3 minutes per month, P<0.001). A total of 17 out of 22 patients saw their arrhythmic burden eliminated or consistently reduced, furthermore two patients underwent a drastic reduction of the average monthly duration of AF (more than 200 minutes compared to the baseline). Only four patients, despite the administration of BDNF, still experienced an arrhythmic burden of 20 minutes or more. Considering the age groups, the major reduction was observed in people aged 70 or more, who were also the most represented in the sample. These results are coherent with the poor literature currently available. CONCLUSIONS: BDNF low dose therapy has shown to have an impacting role in reducing the arrhythmic burden and recurrences of AF, with a particular effectiveness in patients over 70 and without structural heart disease. We should welcome this work, despite it limitations. Further clinical and molecular studies are needed before-considering BDNF low dose as a tool against PAF.
Subject(s)
Atrial Fibrillation , Catheter Ablation , Heart Diseases , Male , Humans , Female , Atrial Fibrillation/drug therapy , Brain-Derived Neurotrophic Factor , Treatment Outcome , Catheter Ablation/adverse effects , Catheter Ablation/methodsABSTRACT
BACKGROUND: Previous studies have shown that patients with heart failure with reduced ejection fraction (HFrEF) and anemia have reduced peak oxygen consumption (VO
Subject(s)
Anemia , Cardiorespiratory Fitness , Heart Failure , Ventricular Dysfunction, Left , Female , Humans , Male , Anemia/epidemiology , Black or African American , Heart Failure/epidemiology , Hemoglobins , Stroke Volume , Ventricular Function, Left , Adult , Middle Aged , AgedABSTRACT
Iatrogenic coronary artery dissections (ICAD) are rare but potentially devastating complications during coronary angiography and percutaneous coronary interventions (PCI). Intima media complex separation may be produced either by the catheter tip or during PCI. Patient characteristics and procedure related risk factors are intimately linked to catheter induced ICAD over diagnostic angiography. Moreover, the increasing complexity of patients undergoing PCI, which frequently involves treatment of heavily calcified or occluded vessels, has increased the likelihood of dissections during PCI. A prompt recognition, along with a prompt management (either percutaneous, surgical or even careful watching), are key in preventing catastrophic consequences of ICAD, such as left ventricular dysfunction, cardiogenic shock, periprocedural myocardial infarction (MI) or cardiac death. This review aims to summarize the main updates concerning the pathophysiology, highlight key risk factors and suggest recommendations in management and treatment of ICAD.
Subject(s)
Coronary Artery Disease , Myocardial Infarction , Percutaneous Coronary Intervention , Humans , Percutaneous Coronary Intervention/adverse effects , Myocardial Infarction/therapy , Myocardial Infarction/complications , Shock, Cardiogenic/etiology , Shock, Cardiogenic/surgery , Coronary Angiography/adverse effects , Iatrogenic Disease , Treatment Outcome , Coronary Artery Disease/therapy , Coronary Artery Disease/diagnosisABSTRACT
Diabetes mellitus (DM) is frequent among heart failure (HF) patients with a further projected increase in prevalence in next years. DM promotes the development of both HF with reduced (HFrEF) and preserved ejection fraction (HFpEF) through different mechanisms. As the general prevalence of both DM and HF is growing worldwide, it is important to define the pathophysiologic mechanisms driving the development of HF in DM patients. These include changes in the cardiac metabolism, mitochondrial dysfunction, impairment in insulin signaling, maladaptive inflammation, coronary microvascular dysfunction, endoplasmic reticulum stress, autophagy suppression, and structural changes, among the main ones. In recent years, novel glucose-lowering treatments, especially sodium-glucose cotransporter 2 inhibitors (SGLT-2is), have shown a strikingly positive impact on the natural history of HF. This has led to a progressive change in choosing SGLT-2is in DM patients at high risk for cardiovascular disease, supported by recent guidelines. The knowledge about novel pathophysiological mechanisms linking DM and HF may open the way to the development of new targeted therapies in the future. In this review, we will summarize general aspects dealing with incidence, prevalence, and pathophysiology of DM in HF patients. As well, we discuss the therapeutic targets to reduce the disease burden and the current evidence of glucose-lowering drugs in patients with DM and HF.
Subject(s)
Diabetes Mellitus, Type 2 , Heart Failure , Sodium-Glucose Transporter 2 Inhibitors , Diabetes Mellitus, Type 2/complications , Diabetes Mellitus, Type 2/drug therapy , Diabetes Mellitus, Type 2/epidemiology , Glucose/therapeutic use , Heart Failure/drug therapy , Heart Failure/epidemiology , Humans , Sodium-Glucose Transporter 2 Inhibitors/pharmacology , Sodium-Glucose Transporter 2 Inhibitors/therapeutic use , Stroke Volume/physiologyABSTRACT
Atrial fibrillation (AF) is responsible for up to one-third of ischemic strokes, with stroke potentially being the first manifestation of a previously undetected AF. Given the efficacy of oral anticoagulants in preventing AF-related ischemic events, searching for unknown AF after stroke requires a comprehensive diagnostic workup. Prospective data have demonstrated the benefits of long-term cardiac monitoring to identify AF in association with cryptogenic stroke, as most strokes are presumed to result from AF. However, strategies of empirical anticoagulation using oral anticoagulants following cryptogenic stroke failed to improve outcomes. We herein summarize contemporary evidence and knowledge gaps on searching for AF after a stroke and the potential secondary prevention strategies to prevent further recurrences.
Subject(s)
Atrial Fibrillation , Ischemic Stroke , Stroke , Anticoagulants/therapeutic use , Atrial Fibrillation/complications , Atrial Fibrillation/diagnosis , Atrial Fibrillation/drug therapy , Humans , Prospective Studies , Stroke/diagnosis , Stroke/etiology , Stroke/prevention & controlABSTRACT
Platypnoea-orthodeoxia syndrome (POS) is an uncommon but challenging clinical condition characterised by positional dyspnoea (platypnoea) and arterial desaturation (orthodeoxia) in the upright position that improve in the supine position. Since its first description, many cases have been reported and many conditions have been associated with this syndrome. Herein, we review the clinical presentation, pathophysiology, diagnostic work-up and management of patients with POS, aiming to increase the awareness of this often misdiagnosed condition.
Subject(s)
Foramen Ovale, Patent , Dyspnea/complications , Dyspnea/etiology , Foramen Ovale, Patent/diagnosis , Foramen Ovale, Patent/diagnostic imaging , Humans , Hypoxia/complications , Hypoxia/etiology , Posture , SyndromeABSTRACT
Over the last decades, inflammation proved to play a pivotal role in atherosclerotic plaque formation, progression and destabilization. Several studies showed that the patients presenting with acute coronary syndrome are at increased risk of adverse cardiovascular events at both short- and long-term follow-up. Results from different clinical trials highlighted that a residual inflammatory risk exist and targeting inflammation is a successful strategy in selected cases associated to an increased inflammatory burden. Recently, the optimization of intracoronary and multimodality imaging allowed to also assess the entity of local inflammation, thus encouraging the individuation of plaque characteristics that portend a higher risk of future cardiovascular events. In this short review, we aim to highlight the role of systemic and local inflammation in acute coronary syndromes, to provide a summarized overview of the possible medical strategies applicable in selected cases and to underline the diagnostic and prognostic potential of multimodality imaging.
Subject(s)
Acute Coronary Syndrome , Coronary Artery Disease , Plaque, Atherosclerotic , Acute Coronary Syndrome/epidemiology , Humans , Inflammation , Plaque, Atherosclerotic/diagnostic imaging , Plaque, Atherosclerotic/epidemiology , Treatment OutcomeABSTRACT
BACKGROUND: Previous studies suggested that N-terminal pro-brain natriuretic peptide (NT-proBNP) level is a powerful independent predictor of death or heart failure (HF) when measured at admission in patients with chest pain or acute coronary syndrome. Little is known about the role of NT-proBNP level measured during a hospitalization for ST segment elevation myocardial infarction (STEMI) in predicting clinical outcomes. We evaluated the optimal NT-proBNP timing (admission, 72 hours, or delta [Δ] NT-proBNP [72 hours minus admission]) to predict 1-year new-onset HF in STEMI patients. METHODS: We measured NT-proBNP levels at admission and 72 hours in 72 patients with STEMI. HF events were adjudicated and defined as hospitalization for HF or need for new initiation of a loop diuretic at 1-year follow-up. Values are presented as medians and interquartile range or frequencies (%) as appropriate. Cox regression analysis was used to determine predictors of adverse events. A receiver-operative-curve was constructed to identify the discriminative value and optimal cut-off points for NT-proBNP. RESULTS: Patients (age 56 [49-64] years, males 59 [82%]) were followed for a median duration of 365 [180-365] days. HF events were recorded in 9 (12.5%) patients. NT-proBNP values at admission, 72 hours, and ΔNT-proBNP were 89 (26-268) pg/mL, 452 (223-1064) pg/mL, and 283 (68-686) pg/mL, respectively. NT-proBNP at 72 hours and ΔNT-proBNP, but not admission NT-proBNP predicted new-onset HF events at follow-up (P=0.03, P=0.002 and P=0.89, respectively). The optimal area under the curve of 0.771 (95%, CI [0.630-0.912], P= 0.009) and cut-off value of 830 pg/mL (sensitivity 79%; specificity 76%) were found for NT-proBNP at 72 hours. The Kaplan-Meier survival curves for NT-proBNP at 72 hours dichotomized above and below this cut-off value, confirmed NT-proBNP at 72 hours >830 pg/mL as predictive of HF events (log-rank statistic = 8.688, P=0.003). CONCLUSIONS: NT-proBNP level at 72 hours and ΔNT-proBNP (72 hours minus admission), but not at time of admission, predicted HF events in patients following STEMI.
Subject(s)
Heart Failure , Natriuretic Peptide, Brain , ST Elevation Myocardial Infarction , Biomarkers , Heart Failure/diagnosis , Heart Failure/epidemiology , Humans , Male , Middle Aged , Natriuretic Peptide, Brain/blood , Peptide Fragments , ST Elevation Myocardial Infarction/diagnosisSubject(s)
Aminobutyrates/therapeutic use , Angiotensin II Type 1 Receptor Blockers/therapeutic use , Biphenyl Compounds/therapeutic use , Heart Failure/prevention & control , Myocardial Infarction/drug therapy , Protease Inhibitors/therapeutic use , Valsartan/therapeutic use , Aminobutyrates/adverse effects , Angiotensin II Type 1 Receptor Blockers/adverse effects , Animals , Biphenyl Compounds/adverse effects , Clinical Decision-Making , Disease Models, Animal , Drug Combinations , Evidence-Based Medicine , Heart Disease Risk Factors , Heart Failure/diagnosis , Heart Failure/mortality , Humans , Myocardial Infarction/diagnosis , Myocardial Infarction/mortality , Neprilysin/antagonists & inhibitors , Protease Inhibitors/adverse effects , Protective Factors , Risk Assessment , Treatment Outcome , Valsartan/adverse effectsABSTRACT
BACKGROUND: Takotsubo syndrome (TS) is an acute, reversible form of heart failure, often mimicking an acute coronary syndrome (ACS). Data regarding racial differences in TS are inconsistent. The aim is to assess clinical features associated with unfavorable in-hospital outcomes between African American (AA) and Caucasian (CAU) patients. METHODS: A retrospective electronic health record query identified 44 AA patients and 110 CAU patients with a diagnosis of TS. Our primary outcome was a composite of death, stroke, and cardiogenic shock during hospitalization. Variables associated with an increased risk of the primary composite outcomes were included in a logistic regression model. RESULTS: Compared to CAU patients, AA patients were a more comorbid population, and presented a higher prevalence of history of illicit drug use (27.3% vs. 13.6% P=0.044). There were no significant differences regarding in-hospital complication rates between AA and CAU patients. In the logistic regression model, infection was associated with greater risk of developing the primary outcome in AA patients (OR=7.26 [95% CI 1.22-43.17], P=0.029), whereas angina was a protective factor (OR=0.11 [95% CI 0.02-0.65], P=0.015). In CAU patients, severely depressed ejection fraction and worse peak creatinine during hospitalization increased risk of developing the primary outcome (OR=5.88 95% CI [2.01-17.17], P<0.001 and OR=1.64 [95% CI 1.15-2.58], P=0.031, respectively). Meanwhile, emotional stressors were protective (OR=0.16 [95% CI 0.03-0.88], P=0.004). CONCLUSIONS: Despite experiencing the same rate of in-hospital complications, the clinical profiles of AA patients are distinct from CAU patients admitted for TS, and clinical variables correlated with worse in-hospital outcomes also differ by race.
Subject(s)
Acute Coronary Syndrome , Takotsubo Cardiomyopathy , Acute Coronary Syndrome/diagnosis , Black or African American , Humans , Retrospective Studies , Takotsubo Cardiomyopathy/epidemiology , White PeopleABSTRACT
BACKGROUND: Recent trials demonstrated the clinical efficacy of sodium-glucose cotransporter-2 inhibitors (SGLT2i) in patients with heart failure (HF), regardless of the presence or absence of type 2 diabetes. These data may allow the use of this innovative drug class in clinical routine for treating these patients. STUDY QUESTION: We aimed at further clarifying the role of SGLT2i in patients with diagnosis of HF, capitalizing on pooled sample size and heightened power for clinically relevant safety and efficacy outcomes. DATA SOURCES: We conducted a systematic search of PubMed, reference lists of relevant articles, and Medline database from inception until March 1, 2021. STUDY DESIGN: This meta-analysis was completed according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. We searched for randomized trials that evaluated the cardiovascular effects of SGLT2i in patients with HF. Three investigators independently assessed study eligibility, extracted the data, and assessed risk of bias. Hazard ratios and 95% confidence intervals (CIs) were pooled and meta-analyzed using a random-effect model. Numbers needed to treat (NNT) with the relative 95% CIs were also calculated. The primary outcome was a composite of HF hospitalization or an urgent visit for worsening HF and cardiovascular death. RESULTS: Three trials were included in the study. Overall, treatment with SGLT2i was associated with a lower risk of the primary composite outcome [hazard ratios 0.73, 95% CI (0.67-0.80), NNT = 11.3]. Similarly, there was a significantly reduced risk of cardiovascular death, all-cause death, HF hospitalization and need for urgent treatment for HF, and HF hospitalization. CONCLUSIONS: Therefore, the available evidence supports the routine use of these drugs as standard-of-care, also given the highly favorable NNTs.
Subject(s)
Cardiovascular Diseases , Diabetes Mellitus, Type 2 , Heart Failure , Sodium-Glucose Transporter 2 Inhibitors , Cardiovascular Diseases/drug therapy , Diabetes Mellitus, Type 2/complications , Diabetes Mellitus, Type 2/drug therapy , Glucose/therapeutic use , Heart Failure/complications , Heart Failure/drug therapy , Humans , Morbidity , Randomized Controlled Trials as Topic , Sodium , Sodium-Glucose Transporter 2 Inhibitors/therapeutic useABSTRACT
INTRODUCTION: Long-term efficacy and safety of either surgical or percutaneous treatment left main coronary artery disease treatment is lacking. EVIDENCE ACQUISITION: We conducted a systematic review and meta-analysis of the most updated randomized clinical trials that compared the efficacy of coronary artery bypass surgery (CABG) or percutaneous coronary intervention (PCI) for the Left Main Coronary Artery (LMCA) disease. It was also conducted a systematic search of PubMed, Google Scholar, reference lists of relevant articles, and Medline. The search utilized the following terms: "left main PCI versus CABG," "drug-eluting stents," "bypass surgery" and "left main stenting." The search of articles compatible with our inclusion and exclusion criteria was performed from inception through April 2020 and returned a combined total of 304 articles. EVIDENCE SYNTHESIS: We identified 6 studies, providing data on 5812 patients. The mean follow-up was 6.7 years. PCI was associated with an increased risk of major vascular events (MACE) (IRR 1.24, 95% CI [1.03-1.67], P<0.01), and coronary revascularization (IRR 1.69, 95% CI [1.42-2.03], P<0.01) compared to CABG. Furthermore, all-cause death, MI and stroke events were not statistically different between the two therapeutic revascularization methodologies (IRR 1.06, 95% CI [0.90-1.24], P=0.47, IRR 1.35, 95% CI [0.84-2.16], P=0.03 and IRR 0.66, 95% CI [0.43-1.01], P=0.05, respectively). CONCLUSIONS: LMCA PCI has an overall same survival compared to CABG in the long term follow-up. Nevertheless, MACE and revascularization events were more frequent in PCI compared to CABG.
Subject(s)
Coronary Artery Disease , Drug-Eluting Stents , Percutaneous Coronary Intervention , Coronary Artery Bypass , Coronary Artery Disease/surgery , Humans , Percutaneous Coronary Intervention/adverse effects , Treatment OutcomeABSTRACT
INTRODUCTION: The impact of omega-3 fatty acids (O3FA) supplementation on cardiovascular risk is still in debate, largely due to the heterogeneity of population enrolled and variable dose and composition of the formulations used in the previous studies. Yet, O3FA may favorably impact on cardiovascular risk by reducing major cardiovascular events (including cardiac death and ischemic events). EVIDENCE ACQUISITION: We aim to perform a comprehensive review of the topic of O3FA for cardiovascular prevention, stemming from a systematic review, to pairwise meta-analysis and network meta-analysis, limiting our inclusion only to randomized clinical trials comparing low dose (LD) (<1 g per day) O3FA and high dose (HD) (>1 g per day) O3FA versus placebo. The efficacy outcomes of interest are total death, cardiac death, sudden cardiac death, myocardial infarction, stroke, coronary revascularization, unstable angina and major vascular events. Safety outcomes of interest are bleeding, gastrointestinal disturbances and atrial fibrillation events. EVIDENCE SYNTHESIS: This meta-analysis is expected to include several important studies on cardiovascular primary and secondary prevention and detail on important cardiovascular outcomes. Furthermore, we intend to highlight safety outcomes related to O3FA supplementation. CONCLUSIONS: The present network meta-analysis results will aid physicians in the decision to prescribe O3FA in patients with or at risk of cardiovascular events. In particular, it will be able to solve controversies emerged from previous randomized clinical trials and meta-analyses regarding the benefit of different doses of O3FA supplementation in the cardiovascular prevention.