A new analysis suggests that patients who receive dual antiplatelet therapy (DAPT) for at least 1 year after coronary stenting are more likely to experience ischemic events than bleeding events, but both types of events are associated with a high risk of death.
Researchers performed a secondary analysis of data from the DAPT study and found that 4% of patients had ischemic events and 2% had bleeding events between 12 and 33 months after stenting.
Both types of events incurred a serious mortality risk—an 18-fold increase after any bleeding event and a 13-fold increase after any ischemic event.
These findings were published in JAMA Cardiology.
“We know from previous trials that continuing dual antiplatelet therapy longer than 12 months after coronary stenting is associated with both decreased ischemia and increased bleeding risk, so these findings reinforce the need to identify individuals who are likely to experience more benefit than harm from continued dual antiplatelet therapy,” said study author Eric Secemsky, MD, of Massachusetts General Hospital in Boston.
For this study, Dr Secemsky and his colleagues analyzed data collected in the DAPT trial, which was designed to determine the benefits and risks of continuing DAPT for more than a year.
The trial enrolled 25,682 patients who were set to receive a drug-eluting or bare-metal stent. After stent placement, they received DAPT—aspirin plus thienopyridine (clopidogrel or prasugrel)—for at least 12 months.
After 12 months of therapy, patients who were treatment-compliant and event-free (no myocardial infarction, stroke, or moderate or severe bleeding) were randomized to continued DAPT or aspirin alone for an additional 18 months. At month 30, patients discontinued randomized treatment but remained on aspirin and were followed for 3 months.
For the present secondary analysis, Dr Secemsky and his colleagues examined data from all 11,648 randomized patients.
During the study period, 478 patients (4.1%) had 502 ischemic events, including 306 myocardial infarctions, 113 cases of stent thrombosis, and 83 ischemic strokes.
The death rate among patients with ischemic events was 10.9% (n=52), and 78.8% of these deaths (n=41) were attributable to cardiovascular causes. The death rate was 0.7% among patients without a cardiovascular event (82/11,082, P<0.001).
The cumulative incidence of death after ischemic events was 0.5% (0.3% with myocardial infarction, 0.1% with stent thrombosis, and 0.1% with ischemic stroke) among the more than 11,600 randomized patients.
The unadjusted annualized mortality rate after an ischemic event was 27.2 per 100 person-years.
When the researchers controlled for demographic characteristics, comorbid conditions, and procedural factors, having an ischemic event was associated with a 12.6-fold increased risk of death (hazard ratio=14.6 for stent thrombosis, 13.1 for ischemic stroke, and 9.1 for myocardial infarction).
Deaths after ischemic stroke or stent thrombosis usually occurred soon after the event, but the increased risk of death from a myocardial infarction persisted throughout the study period.
A total of 232 patients (2.0%) had 235 bleeding events—155 moderate and 80 severe bleeds.
The death rate among patients with bleeding events was 17.7% (n=41), compared to 1.6% among patients without a bleed (181/11,416, P<0.001). However, more than half of the deaths occurring after a bleeding event were attributable to cardiovascular causes (53.7%, n=22).
The cumulative incidence of death after a bleeding event was 0.3% (0.1% with moderate and 0.2% with severe bleeding) in the randomized study population.
The unadjusted annualized mortality rate after a bleeding event was 21.5 per 100 person-years.
When the researchers controlled for demographic characteristics, comorbid conditions, and procedural factors, a bleeding event was associated with an 18.1-fold increased risk of death (hazard ratio=36.3 for a severe bleed and 8.0 for a moderate bleed).
Deaths following bleeding events primarily occurred within 30 days of the event.
“Since our analysis found that the development of both ischemic and bleeding events portend a particularly poor overall prognosis, we conclude that we must be thoughtful when prescribing any treatment, such as dual antiplatelet therapy, that may include bleeding risk,” Dr Secemsky said.
“In order to understand the implications of therapies that have potentially conflicting effects—such as decreasing ischemic risk while increasing bleeding risk—we must understand the prognostic factors related to these events. Our efforts now need to be focused on individualizing treatment and identifying those who are at the greatest risk of developing recurrent ischemia and at the lowest risk of developing a bleed.”
In a previous study, Dr Secemsky and his colleagues developed a risk score using DAPT data that can help determine whether or not DAPT should continue past the 1-year mark.
The tool has recently been included in American College of Cardiology(ACC)/American Heart Association guidelines on the duration of DAPT and is available on the ACC website.