SEATTLE — Low-dose aspirin did not reduce the beneficial effects of ACE inhibitors in patients with atrial fibrillation and a history of heart failure, a subset analysis of 2,031 patients found.
The analysis addressed recurring concerns that aspirin use attenuates the effects of ACE inhibitors in heart failure patients and supported the use of both low-dose aspirin and an ACE inhibitor when indications for both treatments exist, Dr. Akshay S. Desai said at the annual meeting of the Heart Failure Society of America.
Dr. Desai and associates studied data from the Atrial Fibrillation Clopidogrel Trial with Irbesartan for Prevention of Vascular Events (ACTIVE-W). The prospective, open-label study randomized patients with atrial fibrillation to combination antiplatelet therapy with clopidogrel and 75–100 mg/day of aspirin or to oral anticoagulation with warfarin. ACTIVE-W was discontinued early because warfarin clearly reduced the risk of MI, vascular events, or death.
Compared with all ACTIVE-W patients, the 2,031 patients with prior heart failure were more likely to be hypertensive or diabetic; have left ventricular dysfunction, a prior MI, or coronary disease; and be on an ACE inhibitor or angiotensin receptor blocker at baseline. Patients with prior heart failure in ACTIVE-W were twice as likely to develop MI, vascular events, or death, as those with no such history.
Notably, however, the relative benefits of antiplatelet or anticoagulant therapy to prevent thromboembolic events did not differ significantly either in ACTIVE-W patients as a whole or in the subset of patients with heart failure, said Dr. Desai of Brigham and Women's Hospital, Boston. The risk of bleeding complications also did not differ between treatment groups.
Looking at the composite end point of death or hospitalization for heart failure, patients with a history of heart failure carried triple the risk, compared with non-heart failure patients, but again there was no significant difference between the antiplatelet and anticoagulant treatment groups.
The investigators stratified patients with heart failure based on whether they did or did not use an ACE inhibitor at baseline, expecting to see a greater relative benefit in the warfarin group if aspirin attenuated the effects of ACE inhibitors. They found no statistically significant differences between the antiplatelet and anticoagulation groups, suggesting no interaction between aspirin and ACE inhibitors.
Some heart failure patients in the warfarin group also were on ACE inhibitors at baseline, which might have limited the power to detect an aspirin-ACE inhibitor interaction, so they repeated the analyses after excluding patients on an ACE inhibitor at baseline who were randomized to warfarin. Again, they found no significant aspirin-ACE inhibitor interaction.
Concerns about such an interaction began with a 1992 hemodynamic study, later confirmed by others, that showed that coadministration of enalapril and aspirin in 18 patients with severe heart failure attenuated some of the hemodynamic effects of ACE inhibitors on vascular resistance. A retrospective analysis of the SOLVD trial suggested that patients on enalapril were more likely to die if they also took aspirin. A similar finding came from a retrospective analysis of the Scandinavian CONSENSUS II study. A large meta-analysis of ACE inhibitor trials, however, found no significant increase in death or hospitalization for heart failure with concurrent use of aspirin, said Dr. Desai, who has no relationships with the companies that make the drugs he discussed.