SAN FRANCISCO, Calif.—One-year rates of stroke, bleeding and net adverse clinical events for patients with STEMI receiving triple antithrombotic therapy were significantly increased compared with patients receiving dual antiplatelet therapy, according to findings from the HORIZONS AMI trial presented here.

For patients with STEMI, warfarin is prescribed to those at high risk for systemic emboli, said Eugenia Nikolsky, MD, PhD, of the Cardiovascular Research Foundation, New York, N.Y. When undergoing percutaneous coronary intervention (PCI) using stents, these patients may receive triple antithrombotic therapy.

The large-scale randomized HORIZONS AMI trial included 3,317 patients; of those, 105 received triple antithrombotic therapy (aspirin, thienopyridine and warfarin) and 3,212 received dual antiplatelet therapy (aspirin plus thienopyridine).

One-year stroke, bleeding risk

Patients receiving triple antithrombotic therapy had a higher overall incidence of stroke, net adverse clinical events and bleeding (by several definitions) at one year (Table 1).

The one-year ischemic stroke risk was 2.9% vs. 0.08% in patients on dual antiplatelet therapy (P=.03). The hemorrhagic stroke risk was 1% for triple antithrombotic therapy vs. 0% for dual antiplatelet therapy (P=.0002).

"We know from previous trials that it is actually patients who receive warfarin for various indications who have increased bleeding complications, and one of the most dramatic of them is hemorrhagic stroke," Nikolsky said.

Patients on triple antithrombotic therapy also had significantly increased gastrointestinal bleeding compared with patients on dual antiplatelet therapy (4.0% vs. 0.9%, P=.009), Nikolsky said.

Surprisingly, patients in the triple therapy group had a comparatively lower than expected rate of ischemic complications. "This is a high-risk population at baseline because they have poor ejection fraction, larger infarcts and arrhythmia. I would expect these patients to have a worse prognosis compared to patients who are treated with dual antiplatelet therapy."

Similar one-year mortality

However, at one year, the triple and dual therapy groups had similar rates of death, cardiac mortality, reinfarction, stent thrombosis and major adverse coronary event (Table 2).

Nevertheless, Nikolsky cautioned that when prescribing triple therapy, physicians should be aware of the risks. It is critical, she said, to follow the International Normalized Ratio in these patients and not allow them to reach very high anticoagulation levels.

Bleeding is a significant issue in contemporary PCI trials, Nikolsky said. "We know that due to advances in interventional cardiology the rates of ischemic complications like death, myocardial infarctions and target vessel revascularization have decreased, but these are accompanied by a rise in bleeding complications," she said.

This study also raises an important question about drug-eluting stents. Approximately 60% of patients in HORIZONS AMI received a drug-eluting stent, Nikolsky said. With these devices, patients with indications for warfarin must take triple antithrombotic therapy for at least six months. With bare-metal stents, one month would be sufficient.

Nikolsky said that she wonders if drug-eluting stents are necessary in every patient with an MI. “Maybe in this specific group of patients [we should implant] bare-metal stents and not drug-eluting stents,” she said. "If we are going to give them warfarin, we should understand that this combination is more prone to bleeding complications."

Disclosures:

• Dr. Nikolsky reports no relevant conflicts of interest.