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A randomized evaluation of irbesartan versus placebo in patients with Atrial Fibrillation (factorial design of ACTIVE Program)

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Atrial Fibrillation

Presenter | see Discussant report

Salim Yusuf, FESC (Canada)

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List of Authors:
S. Yusuf and S. Connolly on behalf of the ACTIVE Investigators. Population Health Research Institute, McMaster University and Hamilton Health Sciences, Hamilton, Ontario, Canada


One of the strongest risk factors for the development of atrial fibrillation (AF) is elevated blood pressure (BP). Stroke and heart failure which are common complications of AF are also related to elevated BP. Small trials have suggested that blockade of RAAS may be beneficial in AF. However, BP lowering or blockade of the renin-angiotensin-aldosterone system (RAAS) have not been studied in large trials of patients with AF.

We evaluated the comparative effects of irbesartan, an angiotension receptor blocker, (target dose 300mg/day) or placebo given for a mean of 4.1 years, in reducing major vascular events (CV death, MI or stroke: first co-primary) and heart failure (CV death, MI stroke: second co-primary) in 9016 patients with AF receiving usual care. These patients were drawn from two parallel trials (ACTIVE-A and ACTIVE-W) involving over 14,000 patients utilizing a partial factorial design.

BP at entry was 138/75 mm Hg; mean age was 69.5 years. The reduction in BP was modest (-2.6/-1.9 mm Hg) with irbesartan compared to placebo. Irbesartan did not reduce the risk of the first co-primary outcome of CV death, myocardial infarction or stroke (5.4% per year in each group), but there was a lower rate of the second co-primary CV death, MI, stroke and heart failure hospitalizations (7.3% vs 7.7% p= 0.12) with irbesartan, which was chiefly due to a significant reduction in the risk of heart failure hospitalization (3.2% per year in the placebo group versus 2.7% with irbesartan by 14%, p= 0.018). Recurrent event analysis of the second co-primary (39.6% with irbesartan vs. 44.3% with placebo) indicated clearer differences (RR = 0.89, CI = 0.82 to 0.98 ; p = 0.06). Post hoc analysis indicated a significant reduction in the risk of the composite of stroke, non-central nervous system embolism and transient ischemic attacks (3.4% per year in the placebo group versus 2.9% with irbesartan) by 13% (p=0.02), with consistently lower rates of each component of the composite.

The number of admissions in hospital (4055 placebo vs. 3816 irbesartan; p= 0.004) and days hospitalized for cardiovascular reasons were significantly reduced (39,941 placebo vs. 36,480 irbesartan; p=0.0001). Irbesartan was well tolerated with similar rates of drug discontinuation compared to placebo.

The modest BP lowering achieved with irbesartan in this “normotensive” population with AF was associated with reductions in heart failure hospitalizations and thromboembolic events, but not in death or myocardial infarction. These findings suggest that the impact of larger degrees of BP lowering are worth exploring and may potentially lead to larger reductions in thromboembolic events and heart failure.

Discussant | see Presenter abstract





Josep Terradellas, FESC (Spain)

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Presentation slides





A randomized evaluation of irbesartan versus placebo in patients with Atrial Fibrillation (factorial design of ACTIVE Program)

Notes to editor

This congress report accompanies a presentation given at the ESC Congress 2009. Written by the author himself/herself, this report does not necessarily reflect the opinion of the European Society of Cardiology.

The content of this article reflects the personal opinion of the author/s and is not necessarily the official position of the European Society of Cardiology.