Atrial Fibrillation Clopidogrel Trial With Irbesartan for Prevention of Vascular Events (ACTIVE I)

Phase 3

Completed

Brief Summary: The purpose of this study was to determine if Irbesartan compared to Placebo would reduce the risk of vascular events such as heart attack, stroke, non-cerebral thromboembolic event and death in patients with Atrial Fibrillation (AF) and with at least one major risk of vascular events.

Detailed Description: ACTIVE I was one of the 3 separate but related trials of the ACTIVE program conducted in AF patients at risk of vascular events.

Patients were enrolled first into one of the 2 parallel trials of the ACTIVE program evaluating Clopidogrel:

* ACTIVE A comparing clopidogrel + acetylsalicylic acid (ASA) and ASA alone

* ACTIVE W comparing clopidogrel + ASA and oral anticoagulant (OAC).

Then those satisfying additional criteria related to blood pressure and angiotensin receptor blocking agents were re-randomized in the two ACTIVE I arms according to a separate randomization list.

Recruitment & Eligibility

Inclusion Criteria

Should fulfill the eligibility criteria for ACTIVE A or ACTIVE W trial and:

have a systolic blood pressure of at least 110 mmHg
not already receiving an angiotensin receptor blocking agent, unless they are willing and able to be changed to another antihypertensive agent
no previous intolerance to angiotensin receptor blocking agents
no proven indication for angiotensin receptor blocking agents, unless an Angiotensin Converting Enzyme (ACE) inhibitor can be substituted

Exclusion Criteria

Patients will be excluded from ACTIVE study if any of the following are present:

requirement for clopidogrel (such as recent coronary stent procedure)
requirement for oral anticoagulant (such as prosthetic mechanical heart valve)
prior intolerance to acetylsalicyclic acid (ASA) or clopidogrel
documented peptic ulcer disease within the previous 6 months
prior intracerebral hemorrhage
significant thrombocytopenia (platelet count <50 x 10(9)/L)
psychosocial reason making study participation impractical
geographic reason making study participation impractical
ongoing alcohol abuse
mitral stenosis
pregnant or nursing woman or woman of child bearing potential and not on effective birth control for at least one month prior to start of study or not willing to continue on birth control for duration of study
severe comorbid condition such that the patient is not expected to survive 6 months
patient currently receiving an investigational pharmacologic agent
requirement for chronic (> 3 months) non-cyclooxygenase-2 (non-COX-2) inhibitor nonsteroidal anti-inflammatory drug (NSAID) therapy unless willing enrolled in ACTIVE A

Arm && Interventions

Group	Intervention	Description
Irbesartan	Irbesartan	150 mg for 2 weeks, then up-titrated to 300 mg up to final follow-up visit
Placebo	placebo	Matching placebo up to final follow-up visit

Primary Outcome Measures

Name	Time	Method
First Occurence of Any Component of the Composite of Myocardial Infarction, Stroke or Vascular Death as Per Adjudication	Median follow-up of 4.5 years	The first co-primary event is the first occurence of any component of the following cluster over the duration of follow-up: myocardial infarction (nonfatal or fatal), stroke (nonfatal or fatal) or vascular death - after validation by the Event Adjudication Committee (EAC).
First Occurence of Any Component of the Composite of Myocardial Infarction, Stroke, Vascular Death or Hospitalization for Heart Failure as Per Adjudication	Median follow-up of 4.5 years	The second co-primary event is the first occurence of any component of the following cluster over the duration of follow-up: myocardial infarction (nonfatal or fatal), stroke (nonfatal or fatal), vascular death or hospitalization for heart failure - after validation by the EAC.

Secondary Outcome Measures

Name	Time	Method
First Occurrence of Stroke	Median follow-up of 4.5 years	The considered event is the first occurrence of stroke (nonfatal or fatal, ischemic, hemorrhagic or of uncertain type) over the duration of follow-up, after validation by the EAC.
Death From Any Cause	Median follow-up of 4.5 years	The considered event is the death over the duration of the follow-up whatever the cause, cardiovascular or non-cardiovascular.
First Occurrence of Any Heart Failure (HF) Episode	Median follow-up of 4.5 years	The considered event is the first occurence of any HF episode defined as evidence of signs and symptoms of HF with or without hospitalization over the duration of follow-up, as reported by the investigator (i.e. not validated by the Event Adjudication Committee).
First Hospitalisation for Heart Failure (HF)	Median follow-up of 4.5 years	The considered event is the first overnight hospital stay for HF over the duration of the follow-up, after validation by the EAC.
First Hospitalisation for Other Cardiovascular (CV) Cause	Median follow-up of 4.5 years	The considered event is the overnight hospital stay for any CV cause other than Heart Failure over the duration of follow-up, as reported by the investigator (i.e. not validated by the Event Adjudication Committee).