Please select the eligibility criteria that correspond to the clinical trial below.
Title: A Large Scale Clinical Trial Testing the Effects of n-3 PUFA and Rosuvastatin on Mortality-Morbidity of Patients With Symptomatic Congestive Heart Failure
Brief Summary: INTRODUCTION While pharmacological treatments specifically targeted to the cardio-circulatory system have been largely investigated, scanty controlled data are available concerning the role of dietary and metabolic approaches in the management/outcome of patients with heart failure. A large scale, randomized, clinical trial is proposed to test the effects of (a) n-3 PUFA and (b) a lipid lowering agent on top of the best recommended treatments for heart failure.

STUDY DESIGN

The GISSI-HF is a prospective, multicenter, randomized, double blind, placebo controlled study, with randomized allocation of patients with a clinical diagnosis of heart failure to:

Randomization 1 (R1): n-3 PUFA 1 g daily vs corresponding placebo; Randomization 2 (R2): rosuvastatin 10 mg daily vs corresponding placebo.

OBJECTIVES OF THE STUDY PRIMARY OBJECTIVES

To demonstrate that, in patients with heart failure treated at the best of recommended therapies, long term administration of (a) n-3 PUFA, (b) rosuvastatin is more effective than the corresponding placebo in the reduction of:

* All-cause mortality
* All-cause mortality or hospitalizations for cardiovascular reason

OTHER END-POINT MEASURES OF EFFICACY

To assess that long term administration of (a) n-3 PUFA, (b) rosuvastatin is more effective than corresponding placebo in the reduction of:

* Cardiovascular mortality
* Cardiovascular mortality or hospitalizations for any reason
* Sudden cardiac death
* Hospitalizations for any reason
* Hospitalizations for cardiovascular reasons
* Hospitalizations for congestive heart failure
* Myocardial infarction
* Stroke


Options:
A: Inclusion Criteria:

* persistent Atrial Fibrillation (AF) lasting \> one month
* history of at least one AF relapse after previous electrical or Pharmacological cardioversion

Exclusion Criteria:

* left atrium size \> 6 cm
* severe valvulopathy
* myocardial infarction during the previous 6 months
* unstable angina
* NYHA heart failure class IV or hemodynamic instability
* cardiac surgery during the previous 3 months
* significant pulmonary thyroid and hepatic disease
* contraindications to treatment with amiodarone or RASS inhibitors
* chronic renal dysfunction
* QT \> 480 msec in the absence of bundle-branch block
* bradycardia \< 50 b/min
* diagnosis of paroxysmal AF
* hyperkalemia
* pregnancy
* any disease or other medical treatment that, in the opinion of the investigators, could interfere with the study.
B: Inclusion Criteria:

* women aged 35-60 years, men aged 45-60 years
* acceptance of the possibility to be given a placebo and acceptance of the constraints of participation
* lack of previous regular supplementation with any of the vitamins or minerals in the supplement provided
* absence of extreme beliefs or behavior regarding diet

Exclusion Criteria:

* disease likely to hinder active participation or threatened 5-year survival
C: Inclusion Criteria:

* Clinical evidence of heart failure according to the European Society of Cardiology guidelines (New York Heart Association class II-IV) (32)
* Any left ventricular Ejection Fraction (EF) measured within 3 months from enrolment (if EF% \>40%, at least 1 hospital admission for Congestive Heart Failure(CHF) in the previous year)
* No age limits
* Any etiology
* Informed consent (obtained before any study specific procedure)

Exclusion Criteria:

COMMON EXCLUSION CRITERIA (R1=n-3 PUFA vs placebo and R2=rosuvastatin vs placebo):

* Acute Myocardial Infarction, unstable angina or revascularization procedure within 1 month;
* planned cardiac surgery, expected to be performed within 3 months;
* congenital or primary valvular etiology;
* known hypersensitivity to study treatments;
* significant liver disease;
* pregnant or lactating women or women of childbearing potential who are not protected from pregnancy by an accepted method of contraception;
* any condition that in the opinion of the investigator would jeopardize the evaluation of efficacy or safety or be associated with poor adherence to the protocol;
* presence of any non-cardiac disease (e.g. cancer) that is likely to significantly shorten life expectancy;
* treatment with any investigational agent within 1 month before randomization;
* patients already on treatment with n-3 PUFA or statin for whom the prescription is confirmed.

EXCLUSION CRITERIA FOR R2 (statin hypothesis):

* current serum creatinine level \>2.5 mg/dL;
* current ALT, AST level \>1.5 times the upper normal limit;
* current CPK upper normal limits.
D: Inclusion Criteria:

1. Age \> 18 years
2. Written informed consent
3. Non-valvular paroxysmal or persistent AF in whom a rhythm control strategy is planned
4. Duration of at least one symptomatic AF episode \> 10 minutes within the past 6 months
5. ECG documentation of AF

Exclusion Criteria:

1. Chronic AF (continuously present for \> 3 months)
2. Myocardial infarction within the past month prior to selection visit
3. Cardiac or thoracic surgery within the past 3 months or likely to be performed during trial
4. Moderate to severe congestive heart failure (NHYA FC III-IV)
5. Known left ventricular dysfunction (EF\< 40%).
6. Mitral stenosis
7. Moderate to severe mitral insufficiency (Grade 3-4/4)
8. AF secondary to an acute reversible condition (untreated or uncontrolled hyperthyroidism, post- operative AF, fever, anemia)
9. Need for anti-arrhythmic therapy for a condition other than atrial fibrillation
10. Wolff-Parkinson-White syndrome
11. Any medical condition making compliance with study treatment unlikely
12. Current use of n-3 fatty acid supplements or use within the past 3 months
13. Pregnancy, breastfeeding, or possibility of becoming pregnant during the study (Patients must have adequate contraception as determined by the investigator),
14. Participation in another study at the same time or within 30 days of randomization.
15. Uncontrolled hypertension (systolic blood pressure \> 180 mm Hg or diastolic blood pressure \> 110 mm Hg
16. Suspected or known allergy to any ingredients in the study product or placebo, fish or shellfish .

Answer: C