Percutaneous coronary intervention (PCI) is a broadly used therapy for treating coronary artery disease, with over 2 million procedures performed globally annually.[1] Dual antiplatelet therapy (DAPT) with aspirin and a P2Y12 inhibitor is recommended for 6 to 12 months post-PCI. However, shorter durations may be considered, particularly in patients at high bleeding risk, in light of the improved safety profile of new-generation drug-eluting stent (DES) platforms.[2] Afterward, all patients should remain on single antiplatelet therapy lifelong, with most patients continuing aspirin. The need for patients post-PCI to remain on antiplatelet therapy represents a challenge when they require noncardiac surgery (NCS).[3,4] Discontinuation of antiplatelet treatment will expose patients to an increased risk of a thrombotic complication, which can be exacerbated with premature discontinuation of DAPT and the enhanced pro-thrombotic or inflammatory milieu of certain surgeries.[3,4] In turn, continuation of therapy increases the risk of surgical bleeding. With up to 20% of patients requiring NCS within 2 years of their PCI, providing unambiguous recommendations on their antiplatelet management becomes crucial.[3,4]
In the largest, randomized, placebo-controlled trial of perioperative aspirin in patients (n = 10,010) undergoing NCS, administration of aspirin before surgery and throughout the early postsurgical period had no significant effect on the rate of a composite of death or nonfatal myocardial infarction but increased major bleeding.[5] However, in a post hoc analysis of 470 patients who had undergone previous PCI, aspirin use was associated with a significant reduction in death or myocardial infarction, without a significant increase in major bleeding.[6] Guidelines recommend deferring NCS until the required duration of DAPT has been completed. Once the P2Y12 inhibitor has been discontinued, NCS should be performed while on aspirin.[7,8] Aspirin discontinuation should be reserved for patients with high bleeding risk and a comparably low ischemic risk, with procedures performed in PCI-capable hospitals so patients can immediately be treated in case of a perioperative thrombotic event.[7] However, no randomized trial selectively conducted in patients with prior PCI had directly addressed this question. Much of the existing data derive from earlier-generation stent platforms, and some observational studies with newergeneration DES suggest no association between antiplatelet discontinuation and periprocedural adverse cardiac events, raising uncertainty about the robustness of the current guideline recommendations.[9,10]
In this issue of JACC, Kang et al[11] report the results of the ASSURE DES (Aspirin in Patients with Drug- Eluting Stents Undergoing Noncardiac Surgery) trial, which compared a strategy of continuing aspirin monotherapy vs temporarily (5 days) holding all antiplatelet therapy before NCS in patients at least 1 year after PCI with DES.[11] The study tested the hypothesis that continuing would be safer than discontinuing aspirin. Antiplatelet therapy was recommended to be resumed in all participants no later than 48 hours after NCS, unless contraindicated. The primary outcome was a composite of death from any cause, myocardial infarction, stent thrombosis, or stroke between 5 days before to 30 days after NCS. A total of 1,010 patients were randomized. Most surgeries were considered low-to-moderate risk. Among 926 patients in the modified intention-totreat population (462 patients in the aspirin monotherapy group and 464 patients in the no-antiplatelet therapy group), the primary composite outcome occurred in 3 patients (0.6%) in the aspirin monotherapy group and 4 patients (0.9%) in the no antiplatelet group (95% CI: -1.3 to 0.9; P > 0.99). There was no occurrence of stent thrombosis in either group. The incidence of major bleeding did not differ significantly between groups (6.5% vs 5.2%; P = 0.39), while minor bleeding was significantly more frequent in the aspirin group (14.9% vs 10.1%; P = 0.027).
Kang et al[11] should be commended for the execution of the ASSURE DES trial, which deals with a clinically relevant topic that practitioners address on a daily basis. The trial is also the best-randomized evidence available in modern-day PCI practice. However, there are important considerations. The event rate was very low, with events occurring only in 7 patients. The observed incidence of the primary endpoint (0.6% in the aspirin monotherapy group and 0.9% in the no antiplatelet group) were far discordant (ie, approximately 10-fold difference) from the hypothesized assumptions (6.0% for the aspirin monotherapy group and 11.5% for the no antiplatelet therapy group).[11] These assumptions were drawn from a substudy of another clinical trial in which there was postoperative screening of events using biomarkers.[6]
Periprocedural adverse cardiac events in PCI patients undergoing NCS depends on a multitude of factors. In addition to patient-related risk (eg, age, risk factors, comorbidities, functional capacity), angiographic characteristics (eg, PCI complexity, number and length of stents, bifurcation lesions, left main stenting, vessel size, extent of disease, residual disease), time interval from PCI to surgery (ie, increased risk with short interval), and compliance to antiplatelet treatment, the type of surgery also carries important prognostic impact on both ischemic and bleeding events.[12] Indeed, the favorable safety profile of new-generation DES with very low rates of stent thrombosis as shown in this study are encouraging observations. However, in the ASSURE DES trial, most patients underwent low-to-intermediate risk NCS at a median time from PCI of 5.1 years, which could have contributed to the far lower than expected event rates. Moreover, the study was mostly conducted in East-Asian patients, who have a lower risk of ischemic events and higher risk of bleeding compared with other populations.[13] Also, the use of intravascular imaging for guiding PCI procedures is higher in East- Asian countries and could have been a contributing factor in yielding more favorable post-PCI outcomes. These observations underscore that study assumptions should be reflective of anticipated event rates according to the ethnicity of the population under investigation, which was not the case of ASSURE DES.[6,11]
Although minor bleeding was increased in the aspirin monotherapy group, there were no differences in major bleeding or fatal bleeding events. This could be attributed to low-to-intermediate risk of the procedures, more commonly performed with lessinvasive techniques, but also to the fact that the duration of aspirin discontinuation in the no antiplatelet therapy group was only 5 days, which could have mitigated some of the ischemic risk but also hampered any differences in major bleeding complications. Ultimately, the open-label nature of the study, particularly considering that it tested aspirin, should not be dismissed as an important limitation.
In conclusion, the low rate of thrombotic complications observed in ASSURE DES in which low-tomoderate risk NCS were performed after 1 year in PCI patients mostly treated with latest-generation DES are encouraging and are a testament to important advancements in stent safety. However, because of the important considerations on the very low event rates, study design, and type of surgeries performed in ASSURE DES, changes in our routine approach of antiplatelet treatment management in PCI patients undergoing NCS are not yet recommended. Therefore, with few exceptions, maintaining aspirin therapy and abiding by practice guidelines should remain the approach of choice for most PCI patients undergoing NCS until further high-quality data emerge.
J Am Coll Cardiol. 2025;84(24) © 2025 American College of Cardiology Foundation