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:

Patients who meet all of the following criteria.

* Patients with NYHA class II through IV chronic heart failure.
* Patients who have a history of hypertension or those who have antihypertensive medications.
* Patients who are aged 20 years or older and less than 80 years at the entry.
* Stable patients who have angiotensin converting enzyme inhibitor and/or beta-blocker.
* Patients who do not have angiotensin II receptor blocker.

Exclusion Criteria:

* Patients who have renal dysfunction (serum creatinine \>=3.0mg/dL) or those who are receiving chronic hemodialysis.
* History of drug hypersensitivity to olmesartan.
* Patients who have severe liver dysfunction.
* History of angioedema.
* History of malignant tumor or life-threatening illness of poor prognosis.
* Pregnant or possibly pregnant patients.
* Cardiovascular surgery within 6months prior to the date of the entry.
* Acute myocardial infarction within 6 months prior to the date of the entry.
* Percutaneous coronary intervention or stent implantation within 6 months prior to the date of the entry.
* Other patients deemed unsuitable as subjects of the study by the treating physician.
B: Inclusion criteria:

Male or female subjects 55 year or older who have suffered an ischemic stroke within the past 90 days and who meet all other inclusion criteria. Include also patients of ages 50 - 54 years and/or 90 to 120 days after the qualifying stroke provided the patient has at least two of the following additional risk factors:

* Diabetes mellitus
* Hypertension (systolic BP ¿ 140 or diastolic BP ¿ 90)
* Smoker at time of qualifying stroke
* Obesity (BMI\>30; BMI=weight (kg)/\[height (m)\]2)
* Previous vascular disease (stroke, MI, or peripheral arterial disease prior to qualifying stroke)
* End-organ-damage (retinopathy, LVH, or microalbuminuria)
* Hyperlipidemia

Exclusion criteria:

hemorrhagic stroke (must be ruled out by imaging);unable to give informed consent; known brain tumor, severe renal or hepatic insufficiency, current active peptic ulcer disease, severe coronary artery disease including unstable angina pectoris or an MI within the previous 3 months,or history of a hemostatic disorder or systemic bleeding ;hyperkalemia;uncorrected volume or sodium depletion; pre-stroke history of dementia;modified Rankin score greater than 4;qualifying stroke induced by surgical or cardiovascular procedure;uncontrolled hypertension at entry above 180/110 mmHg (goal BPs are lower); SBP 120 mmHg or less for hospitalized patients; currently taking an ARB and not able or willing to switch to alternative; required or planned continuing treatment with antithrombotics or anticoagulants including heparin or warfarin or non-study platelet inhibitors; syndrome of asthma, rhinitis and nasal polyps;scheduled for major surgery, carotid endarterectomy, or carotid angioplasty (4 weeks post surgery is allowed);unlikely to be released from hospital following the qualifying stroke or presence of a severe disability likely to lead to being bedridden or demented or a non-vascular disease or condition which makes it unlikely that the patient will survive to the end of the trial; history of thrombocytopenia or neutropenia.
C: Inclusion Criteria:

* as above

Exclusion Criteria:

* patients with a history of ischaemic heart disease, heart failure, cerebrovascular disease, peripheral arterial disease or congenital coronary anomalies, prior to entry into the cohort
* patients with symptoms of chest pain in the 6 months prior to cohort entry
* patients \< 35 or \>100 years of age after eligibility for entry to the cohort
D: 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.

Answer: D