A large analysis shows that beyond the first year, adverse events continue to accrue at a rate of approximately 2% per year for up to 5 years after PCI, whether with bare-metal stents or first- or second-generation drug-eluting stents.
An analysis of patient-level data from 19 randomized trials of metallic drug-eluting stents (DES) found that very late stent-related ischemic events continued to accrue at a rate of approximately 2% per year between 1 and 5 years after percutaneous coronary intervention (PCI).
The study by Mahesh V. Madhavan, MD, of New York-Presbyterian Hospital/Columbia University Irving Medical Center, and colleagues, also showed that the rate of very late stent-related ischemic events did not meaningfully improve as stent technology evolved from bare-metal stents to contemporary DES, with no plateau evident for ongoing risk, signifying a lifelong patient concern.
However, major adverse cardiac events (MACE) and target lesion failure, defined as cardiac death, target-vessel MI, or ischemia-driven target lesion revascularization, did progressively fall over the first year post-procedure as technology evolved.
While stent-related MACE within the first year following PCI is well-studied, the authors sought to shed light on very late events post-PCI. Before Madhavan and colleagues’ paper, what long-term follow-up was available came from studies like TAXUS or SIRTAX, both with early drug-eluting stents, which the authors said lacked the power to demonstrate differences in very late hard events.
To gain the size that would permit event analysis, Madhavan and colleagues pooled individual patient data from 19 randomized metallic stent trials to evaluate very late MACE, a composite of cardiac death, myocardial infarction (MI), or ischemia-driven target lesion revascularization (TLR) that occur beyond 1 year post-procedure. Their results were published in the Feb. 18 issue of the Journal of the American College of Cardiology.
Among 25,032 total patients, 47% (n = 11,686) received devices used in contemporary practice.
Beyond the Target
While the study authors called for improvements in stent technology and implantation technique, that will likely have minimal impact on very late risk, according to Manel Sabaté, MD, PhD (Hospital Clínic de Barcelona), and Michael Mack, MD (Baylor Scott & White Health, Dallas). In an accompanying editorial commentary, Sabaté and Mack estimated that only up to 40% of all events occurring between 1 and 5 years could be considered stent-related.
The editorialists based this estimate on the predictors of very late events, which include the following: use of first-generation DES, age, coronary risk factors such as diabetes or smoking, and variables associated with extensive disease (previous revascularization either by PCI or coronary artery bypass graft surgery, calcified vessels, multivessel treatment, and small vessels).
Given that list, Sabaté and Mack differentiated potentially stent-related events from those probably not related to the device. The first category would include cardiac death, target-vessel MI, and ischemia-driven TLR; among the latter, the list includes noncardiac death, nontarget vessel MI, and nontarget vessel revascularization.
Thus, the majority of very late events occur remote from the PCI site, suggesting a need for a more a systemic approach. Targeting coronary risk factors would include greater use of high-intensity statin therapy, even further lowering of low-density lipoprotein cholesterol (as suggested by improved outcomes when PCSK9 inhibitors are added to statin therapy), prolongation of dual antiplatelet therapy when appropriate, and new agents (like SGLT2 inhibitors) that improve metabolic control in patients with diabetes but have a greater impact on improving cardiovascular outcomes than explained by metabolic control alone.
Sabaté and Mack added in their editorial that the results reported by Madhavan and colleagues suggest a reassessment of how outcomes should be reported in future trials.
“It becomes clear from this pooled patient analysis that there is currently a need for assessing outcomes on a patient level rather than on a lesion level,” Sabaté and Mack wrote.
Therefore, they said, future trials should focus more on the overall clinical strategy than on a specific device, and “outcomes should be clearly defined as target, nontarget, and overall, and as device- or technique-related and nondevice- or nontechnique-related.”
Madhavan MV, Kirtane AJ, Redfors B, et al. Stent-Related Adverse Events >1 Year After Percutaneous Coronary Intervention. J Am Coll Cardiol 2020;75:590-604.
Sabaté M, Mack M. Very Late Outcomes After Stent Implantation: It Is Time to Target the Nontarget Sites. J Am Coll Cardiol 2020;75:605-7.