By Jeffrey Zimmet, MD, PhD

Associate Professor of Medicine, University of California, San Francisco; Director, Cardiac Catheterization Laboratory, San Francisco VA Medical Center

Dr. Zimmet reports no financial relationships relevant to this field of study.

SYNOPSIS: Approximately one in eight patients who undergo successful percutaneous coronary intervention will suffer myocardial infarction, stent thrombosis, or a clinically relevant bleeding event within two years.

SOURCE: Brener SJ, Kirtane AJ, Stuckey TD, et al. The impact of timing of ischemic and hemorrhagic events on mortality after percutaneous coronary intervention: The ADAPT-DES study. J Am Coll Cardiol Interv 2016. pii: S1936-8798(16)30491-5. doi: 10.1016/j.jcin.2016.04.037. [Epub ahead of print].

Among patients undergoing percutaneous coronary intervention (PCI) in the contemporary era, some will experience serious ischemic or bleeding events in the subsequent two years, according to the ADAPT-DES study. ADAPT enrolled 8,582 patients following successful PCI from 11 sites in the United States and Germany. All patients were placed on dual antiplatelet therapy with aspirin and clopidogrel, and platelet reactivity was measured with the VerifyNowpoint-of-care assay. The primary purpose of the study, which has been published previously, was to detect differences in stent thrombosis in patients with high on-treatment platelet reactivity. The purpose of the analysis of the ADAPT-DES study was to assess the importance of the timing of the adverse events after PCI on outcomes.

Patients were followed by office or phone visits out to two years, and events, including myocardial infarction (MI), stent thrombosis, and clinically relevant bleeding, were tracked and adjudicated. After two years of follow-up, 1,060 patients (12.4% of the original 8,582) had experienced one or more of these events, 691 experienced serious bleeding (of which 261 occurred prior to hospital discharge), 294 suffered a MI not related to stent thrombosis, and 75 had definite or probable stent thrombosis. Patients who experienced events presented with more risk factors for coronary disease than those who did not. Overall, these patients underwent more complex procedures, with more stents implanted per patient, and more vessels and lesions treated. Unsurprisingly, patients with interrupted dual antiplatelet therapy at one and two years were more likely to experience clinically important bleeding at these time points.

Each of the tracked complications carried an increased risk of death, with the highest mortality (27.2%) observed among patients with stent thrombosis. An intermediate risk of death was noted in patients with either MI or significant bleeding (12.4% and 10.5%, respectively), while the lowest mortality (2.7%) occurred in patients without any events. Among patients with stent thrombosis, event timing clearly was related to mortality risk, with 38.5% of patients who developed early stent thrombosis (≤ 30 days) dying within 30 days of the event vs. 15.3% of those whose events occurred late (30-365 days) and 20.0% of those whose events occurred very late (beyond 365 days). Investigators observed a reverse pattern among patients with MI that was not associated with stent thrombosis, with only a 0.8% mortality risk with early MI, vs. 5.1% and 7.5% mortality in patients with late and very late MI. By stepwise, multivariate modeling, all three types of event — stent thrombosis, clinically important bleeding, and MI — were independent predictors of death within two years of the index PCI.

The study concluded that post-PCI ischemic and hemorrhagic events are associated with an increased mortality risk, which is highest in those with stent thrombosis. With regard to event timing, the risk of death is greatest in those with early stent thrombosis and in those with very late spontaneous MI.

COMMENTARY

There is nothing particularly groundbreaking about this study. Indeed, it should not surprise clinicians that bleeding, stent thrombosis, and MI occur after PCI and are associated with an elevated risk of death. Rather, the main utility of this study is to provide remarkably clear insight into the risks and timing of adverse events following MI in the contemporary era. In this study, which included a real-world mix of patients and procedures, just over 12% of patients experienced a major bleeding or ischemic event within two years of their PCI procedure. Bleeding accounted for a majority of events, and two-thirds of bleeding episodes occurred after hospital discharge.

When counseling patients following PCI, it is important clinicians have accurate data to convey. In particular, the concept that significant risk remains in the years following PCI is important. The devastating consequences of early stent thrombosis suggests a need for close follow-up in the early period, but with continued monitoring of lower intensity over time. The one-in-eight risk of serious events is something to which a majority of patients can relate in an intuitive manner.