Photo courtesy of the CDC
A new study suggests less is more when it comes to antithrombotic therapy for higher-risk older patients with atrial fibrillation who have a heart attack and undergo percutaneous coronary intervention (PCI).
At 2 years of follow-up, patients who had received triple therapy—warfarin, aspirin, and P2Y12 inhibitor—after PCI had similar rates of major adverse cardiac events (MACE) as patients who received dual antiplatelet therapy (DAPT)—aspirin and P2Y12 inhibitor.
But patients on triple therapy had a higher incidence of intracranial hemorrhage and bleeding that required hospitalization.
These results appear in the Journal of the American College of Cardiology alongside a related editorial.
Researchers examined data from the National Cardiovascular Data Registry ACTION Registry-GWTG linked with Centers for Medicare and Medicaid Services data, looking at records from January 2007 through December 2010.
They identified 4959 patients aged 65 and older with a history of atrial fibrillation who presented with acute myocardial infarction (MI) and underwent PCI. Most patients (72.4%, n=3589) were discharged on DAPT, but 27.6% (n=1370) were discharged on triple therapy.
In the DAPT arm, 97.2% of patients (n=3490) received clopidogrel, 2.5% (n=89) received prasugrel, and 0.3% (n=10) received ticlopidine. In the triple therapy arm, 98.2% of patients (n=1346) received clopidogrel, 1.4% (n=19) received prasugrel, and 0.4% (n=5) received ticlopidine.
Patients receiving triple therapy were more likely to be male, have a history of either angioplasty or coronary artery bypass surgery, and have a history of stroke. These patients were frequently already on warfarin before they were admitted to the hospital.
Patients who were released on DAPT were more likely to have had an in-hospital major bleeding event.
Incidence of MACE
Two years after discharge, the risk of MACE—death, hospital readmission for MI, or stroke readmission—was similar between the DAPT and triple therapy arms. The unadjusted cumulative incidence rate of MACE was 32.6% in the triple therapy arm and 32.7% in the DAPT arm (P=0.99).
The unadjusted cumulative incidence rates of the individual MACE components were also similar between the triple therapy and DAPT arms. All-cause mortality occurred in 23.8% and 24.8%, respectively (P=0.70), MI readmission occurred in 8.5% and 8.1%, respectively (P=0.54), and stroke readmission occurred in 4.7% and 5.3%, respectively (P=0.23).
After the researchers adjusted for patient, treatment, and hospital characteristics, there was still no significant difference between the arms with regard to the incidence of MACE or MACE components.
The adjusted hazard ratio (HR) was 0.99 for MACE (P=0.94), 0.98 for all-cause mortality (P=0.82), 1.03 for MI readmission (P=0.83), and 0.85 for stroke readmission (P=0.38).
Bleeding incidence
The cumulative incidence of bleeding requiring hospitalization within 2 years of discharge after PCI was significantly higher for the triple therapy arm than the DAPT arm—17.6% and 11.0%, respectively (P<0.0001).
The difference remained significant after the researchers adjusted for patient, treatment, and hospital characteristics. The adjusted HR was 1.61 (P<0.0001).
Similarly, the unadjusted cumulative incidence of intracranial hemorrhage was significantly higher for the triple therapy arm than the DAPT arm—3.4% and 1.5%, respectively (P<0.001).
This difference remained significant after adjustment. The adjusted HR was 2.04 (P<0.01).
“The increased risk of bleeding without apparent benefit of triple therapy observed in this study suggests that clinicians should carefully consider the risk-to-benefit ratio of triple therapy use in older atrial fibrillation patients who have had a heart attack treated with angioplasty,” said Connie N. Hess, MD, of the Duke University School of Medicine in Durham, North Carolina.
“Further prospective studies of different combinations of anticlotting agents are needed to define the optimal treatment regimen for this population.”
