 |
|
Salim Yusuf: “Heart failure a neglected
complication of atrial fibrillation.”
|
Findings from the ACTIVE-I (Atrial fibrillation clopidogrel trial with irbesartan for prevention of vascular events) study suggest that the angiotensin receptor blocker (ARB) irbesartan could reduce hospitalisation for heart failure by 14%. Yusuf stressed the importance of the finding, describing heart failure as a “neglected complication” of atrial fibrillation.
The ACTIVE programme includes people with documented AF who have at least one further risk factor, such as age above 75 years or hypertension. Almost half of the total group were on warfarin; all were on antiplatelet therapy.
The Hot Line trial, ACTIVE-I, included 9016 of the group, in a partial factorial design. Patients were randomised to receive either placebo, or 300 mg/day irbesartan on top of the other therapy received. At analysis, the irbesartan group had a slightly greater reduction in blood pressure than those on placebo (3/2 mmHg).
The primary outcomes of the study were not met. There were exactly the same number of first events (stroke/MI/vascular death), 963, in each group. A co-primary endpoint which also included hospitalisation for heart failure showed a non-significant trend in favour of irbesartan over placebo.
However, a significant benefit for irbesartan was achieved when the secondary endpoint of reducing heart failure hospitalisation was considered alone (HR 0.86, 95% CI 0.76-0.98, p=0.018).
Post hoc analyses suggested, first, that the commonest complication in the group was not stroke, but heart failure. Further, there was a reduction in strokes in the irbesartan group of up to 40% when primary haemorrhagic and secondary transformation of ischemic stroke were considered together. “Maybe even a small lowering of blood pressure will prevent intracranial bleeds,” Yusuf said.
“Although we did not reach our primary endpoint,” he continued, “the study shows that in this population where 80% of patients have hypertension, it makes sense to use an ARB because it reduces heart failure, the commonest complication. And perhaps it also reduces the risk of intracranial bleeds which is a devastating complication when we use antithrombotic therapy.”
Yusuf stressed the need for “total management” of the patient: “So far we have only focused on preventing strokes through antithrombotic drugs. We need to reduce stroke, but we also need to reduce heart failure and control blood pressure - as well as prevent rate and rhythm problems. In the future, this may be a package for these patients.”