Whilst reducing blood pressure reduces the risk of heart failure and stroke this relationship has thus far not been demonstrated in patients with atrial fibrillation. \u00a0This is despite the fact that recent mechanistic work and retrospective analyses have suggested that both ACE inhibitors and ARBs have specific properties that alter atrial mechanical and electrical remodelling and may prevent atrial fibrillation.<\/p>\n
To formally test whether these effects translate into clinical gains, in the ACTIVE I study, the authors recruited 9016 patients with permanent or paroxysmal AF at increased risk of stroke, who were randomly assigned to receive the ARB irbesartan at a target dose of 300 mg once daily or double-blind placebo.\u00a0 ACTIVE I was the sister trial of the ACTIVE W and ACTIVE A trials which compared various combinations of aspirin, clopidogrel and warfarin in the same patients with these stratifications being accounted for in the statistical analysis. \u00a0The first co-primary outcome was a composite of stroke, myocardial infarction, or death from vascular causes; the second was this composite plus hospitalization for heart failure.\u00a0 Patients were followed up for a mean of 4.1 years.\u00a0 About 60% of patients were already taking an ACE inhibitor at enrolment and these were continued.<\/p>\n
Irbesartan reduced blood pressure by a mean of 2.9\/1.9 mmHg compared with placebo but this failed to reduce the composite of stroke, MI or vascular death which occurred at a rate of 5.4% per 100 person-years in both groups (HR with irbesartan, 0.99; 95% CI, 0.91 to 1.08; P=0.85).\u00a0 Similarly there was no difference in the second co-primary outcome which occurred at a rate of 7.3% per 100 person-years among patients receiving irbesartan and 7.7% per 100 person-years among patients receiving placebo (HR, 0.94; 95% CI, 0.87 to 1.02; P=0.12).\u00a0 In the prespecified secondary outcome of first hospitalization for heart failure irbesartan appeared to show a marginal benefit (HR for irbesartan, 0.86; 95% CI, 0.76 to 0.98;P=0.02) but this came at the increased risk of symptomatic hypotension (127 vs. 64;P<0.001) and renal dysfunction (43 vs. 24;P=0.02) with 4 patients in the irbesartan group requiring dialysis against none in the placebo group.\u00a0 Finally, there was no benefit from irbesartan in preventing recurrence of AF or hospitalisation for AF.<\/p>\n
Conclusions<\/strong><\/p>\n In this large multi-centre study, irbesartan did not further reduce cardiovascular events in patients with atrial fibrillation or promote maintenance of sinus rhythm when added to conventional therapy.<\/p>\n