• Cerebrovascular Disease
• Hypertensive Disease
• Arrhythmias Clinical Trials

In the Atrial Fibrillation Clopidogrel Trial with Irbesartan for Prevention of Vascular Events (ACTIVE-I; NCT00249795), treatment with irbesartan failed to lower the risk of stroke, myocardial infarction (MI), and vascular death compared with placebo in patients with atrial fibrillation (AF). However, irbesartan may have a role in preventing heart failure (HF), recurrent embolic events, and cardiovascular (CV) hospitalizations in patients with AF.

The ACTIVE program comprised three clinical trials that enrolled patients with documented AF and at least one additional risk factor for stroke, including ACTIVE-W (clopidogrel plus aspirin vs warfarin), ACTIVE-A (clopidogrel plus aspirin vs aspirin monotherapy), and ACTIVE-I. Salim Yusuf, MD, DPhil, McMaster University, Ontario, Canada, presented preliminary results from the ACTIVE-I trial, which was designed to evaluate the effect of additional blood pressure (BP) reduction with an angiotensin receptor blocker (ARB) on common complications of AF, including HF, stroke, and other embolic events.

In ACTIVE-I, patients who had a systolic BP >110 mm Hg and were not being treated with an ARB were randomly assigned to irbesartan at a target dose of 300 mg/day (n=4518) or placebo (n=4498). At baseline, patients generally were treated with multiple CV medications, including angiotensin-converting enzyme (ACE) inhibitors (60%), aspirin (59%), beta-blockers (54%), diuretic therapy (54%), vitamin K antagonists (38%), digoxin (35%), calcium channel blockers (27%), and antiarrhythmics (23%).

On top of this extensive background therapy, irbesartan provided an additional reduction in BP (6.8/4.5 mm Hg) compared with placebo (3.9/2.6 mm Hg). However, ACTIVE-I failed to reach either of its two primary endpoints. The composite endpoint of stroke, MI, and vascular death occurred with equal frequency in the irbesartan and placebo groups (HR, 0.99; p=0.85), and a similar proportion reached the composite co-primary endpoint of the above plus HF hospitalization (HR, 0.94; p=0.12). Only one component of the primary endpoint, HF hospitalization, occurred less frequently in the irbesartan group (HR, 0.86; p=0.018).

Compared with placebo, irbesartan was associated with a similar frequency of total strokes (2.3% vs 2.1%; p=0.21) but fewer hemorrhagic strokes (0.2% vs 0.4%; p=0.010). Irbesartan also reduced the composite endpoint of stroke, transient ischemic attacks, and noncentral nervous system embolism (HR, 0.87; p=0.024). In particular, the reduction of recurrent embolic events in the irbesartan group (39.6% vs 44.3%; p=0.016) contributed to significantly fewer CV hospitalizations (3817 vs 4509 admissions; p=0.003) and fewer total days of hospitalization (36,440 vs 39,971 days; p<0.001) compared with placebo.

Findings from ACTIVE-I illustrate the limited benefit of a modest reduction in BP with irbesartan in the setting of AF, in which the prevalence of hypertension is high and HF is more common than stroke, Dr. Yusuf said. More aggressive BP lowering with multiple antihypertensive agents may result in an even greater clinical benefit, he concluded.

• © 2009 MD Conference Express