ACTIVE-I: Irbesartan linked with reduced HF complications, embolic events in patients with AF

But no major reduction in CV events was reported.

European Society of Cardiology Congress 2009

Patients with atrial fibrillation assigned irbesartan experienced BP-lowering and reductions in HF hospitalization and thromboembolic events.

Researchers for the ACTIVE-I trial enrolled 9,016 patients with AF drawn from the ACTIVE-A and ACTIVE-W trials. Patients were randomly assigned to receive either irbesartan (Avapro, Sanofi-Aventis/Bristol-Meyers Squibb) plus conventional AF therapy (n=4,518) or placebo (n=4,498). The co-primary endpoints included a reduction in major vascular events (CV death, MI or stroke) and a reduction in major vascular events plus HF hospitalization. Patients were followed-up for a mean of 4.1 years.

According to the study results, irbesartan was not associated with a reduction in the first co-primary endpoint of major vascular events (5.4% per year in each group, P=.846). There was a slight reduction in the second co-primary endpoint of major vascular events plus HF hospitalization (7.3% in the irbesartan group vs. 7.7% in the placebo group, P=.122) due to a 14% reduction in the risk for HF hospitalization in the irbesartan group vs. the placebo group (2.7% vs. 3.2%, P=.018). Recurrence of the second co-primary endpoint of major vascular events plus HF hospitalization was lower in the irbesartan group vs. placebo (39.6% vs. 44.3%; RR=0.89; 95% CI, 0.82-0.98). A post hoc analysis revealed a 13% reduction in the composite of stroke, non-central nervous system embolism and transient ischemic attack in patients taking irbesartan vs. placebo (2.9% vs. 3.4%, P=.02).

“The implications for this study are that patients with AF have other complications, especially HF, that are common,” Salim Yusuf, MD, a professor of medicine at McMaster University in Ontario, concluded in his presentation. “It would be reasonable to lower BP perhaps with an angiotensin receptor-blocker like irbesartan, and it is quite possible that more aggressive BP lowering with multiple antihypertensive agents used together might lead to substantial reduction in HF and several vascular disease to a greater extent.”

In the discussant portion of the presentation, Josep Brugada Terradellas, MD, a cardiologist at Hospital Clinic i Provincial de Barcelona in Spain, said that despite the modest risk reductions achieved by irbesartan, it did not add much to the range of BP-lowering therapies available for patients with AF.

“In a population with normal BP and who remain in AF, irbesartan lowers BP to a modest extent with no significant impact on outcomes of stroke, MI, vascular death or HF hospitalization combined,” Terradellas said in his presentation. “Treatment with irbesartan, in my view, does not add to the treatment of a heterogeneous population with differing forms of AF already treated with BP-lowering drugs.”

For more information:

Yusuf S. Session 3586-3587. Presented at: European Society of Cardiology Congress; Aug. 29-Sept. 2, 2009; Barcelona.