Antithrombotic Treatment Regimens in Patients Undergoing Percutaneous Coronary Revascularization Requiring Oral Anticoagulation: What Real-World Evidence Shows Us

In patients undergoing percutaneous coronary intervention (PCI), dual antiplatelet therapy (DAPT) with aspirin and P2Y12 inhibitor is the standard of care for the prevention of thrombotic complications.1 However, there are a growing number of patients undergoing PCI who are at risk of thromboembolic events, such as those with atrial fibrillation (AF), pulmonary embolism, or mechanical prosthetic valves, who also require oral anticoagulation (OAC).2 This poses a critical therapeutic dilemma on the optimal antithrombotic treatment for these patients. In fact, although the theoretical need for adding an OAC to DAPT, known as “triple antithrombotic therapy” (TAT), may provide overall greater antithrombotic protection, it inevitably leads to an increased risk of bleeding.3 Importantly, bleeding carries relevant prognostic implications, including increased mortality, underscoring the need for antithrombotic treatment regimens associated with reduced bleeding while preserving efficacy.4 Results from randomized clinical trials have consistently shown that early discontinuation (eg, from hospital discharge up to 1 week post-PCI) of aspirin and starting dual antithrombotic therapy (DAT) consisting in the combination of an OAC (preferably a direct-acting OAC or DOAC), plus a P2Y12 inhibitor (most commonly clopidogrel), to be associated with reduced bleeding compared with TAT.3 Although there was no apparent increase in ischemic events with this treatment regimen, these studies were not individually powered to detect differences. However, meta-analyses suggest an increase in thrombotic complications in patients on DAT, which may be accentuated in those presenting with an acute coronary syndrome (ACS).3 In light of these observations, recent guidelines recommend a “short” TAT duration (eg, up to 1 week) in most patients, with the exception of those with a thrombotic risk that outweighs the bleeding risk, for whom TAT up to 1 month can be considered.5,6 However, in real-world practice, patients are of greater complexity than those enrolled in clinical trials and understanding how these recommendations are applied are of utmost interest. In this issue of the Journal, Sciahbasi and coauthors aimed at evaluating contemporary real-world data on antithrombotic regimens and outcomes in patients on OAC undergoing PCI with stent implantation.7 The study is a prospective, observational registry conducted at 25 centers in Italy. The primary end point was net adverse clinical events (NACE), defined as a composite of major bleeding and major adverse cardiac and cerebral events (MACCE), including unplanned target vessel revascularization, myocardial infarction, stent thrombosis, stroke, or transient ischemic attack, and all cause death in patients on vitamin-K antagonists versus DOAC at 1-year follow-up. The secondary prespecified end point was NACE with DAT versus TAT at follow-up. The study included 1234 patients, of whom 6 died during hospitalization. Most patients presented with ACS (n = 783 [64%]), of whom 22% of the total population were admitted with an ST-segment elevation acute myocardial infarction. Of patients discharged alive (n = 1228), 86% had AF as the reason for using OAC, and 1006 (82%) were on a DOAC. Clopidogrel was the P2Y12 inhibitor of choice being used in 99% of patients. The authors found that the rate of NACE was significantly higher with vitamin-K antagonists compared with a DOAC (23% vs. 16%, P = 0.013), a result which was mainly driven by MACCE (19% vs. 13%, P = 0.031), particularly by all-cause death (16% vs. 9%, P = 0.003). At discharge, only 97 patients were on DAT versus 1028 patients on TAT. The median TAT duration was 39 days (interquartile range 30–154 days). Of interest, TAT and DAT did not differ regarding NACE (17% vs. 19%, P = 0.864) at follow-up, despite a lower rate of major bleeding (2% vs. 5%, P= 0.014) and a higher rate of MACCE (13% vs. 19%, P = 0.021) observed among patients on DAT versus TAT. Of note, the mean CHA2DS2-VASc and HAS-BLED scores were higher in the DAT versus TAT groups (4.6 ± 1 vs. 4.1 ± 2, P < 0.001 and 3.8 ± 1 vs. 3.6 ± 1, P = 0.001, respectively), underscoring a possible higher clinical complexity among the former (Fig. 1).FIGURE 1.: Antithrombotic treatment regimens and outcomes in patients on OAC undergoing PCI in the study by Sciahbasi and co. IHD, ischemic heart disease; LV, left ventricle; VKA, vitamin-K antagonists.The study by Sciahbasi and coauthors provides important information on patterns of antithrombotic treatment regimens being used in patients undergoing PCI also requiring OAC in real-world clinical practice. The study results show how AF is the most frequent patient cohort incurring this issue. Indeed, the frequent overlap in risk factors for AF and coronary artery disease and the growing prevalence of AF can be important contributing factors. Notably, as per guideline recommendations, a DOAC was used in most of these patients, and the current registry confirms the overall superiority of a DOAC-based regimen. However, most patients were discharged on TAT rather than DAT and the duration of TAT was rather long (median 39 days; interquartile range 30–154 days), frequently exceeding that recommended by guidelines. Trial data have shown that, although prolongation of TAT up to 30 days reduces ischemic events at the expense of increase bleeding (ie, trade-off model), beyond 30 days there is no ischemic benefit while the risk of bleeding continues to increase.8 The more favorable safety profile of a DAT regimen is confirmed in this analysis and may represent an opportunity for those centers prolonging TAT to revisit their treatment recommendations. Indeed, it may be argued that in this registry, a considerable proportion of patients needing TAT presented with an ACS (64% of the overall study population). It cannot also be excluded that the angiographic complexity of these patients was greater than patients enrolled in clinical trials. Despite this, clopidogrel was used in 99% of patients and, although being the preferred P2Y12 inhibitor in PCI patients requiring OAC, a higher use of prasugrel or ticagrelor would have been expected. The high use of clopidogrel, known to be associated with less potent and predictable antiplatelet effects, could also explain why TAT duration was particularly prolonged in this registry. Ongoing studies will further determine if DAT with a potent P2Y12 inhibitor for 1 month, followed by an unguided de-escalation to clopidogrel will reduce the ischemic events without an increase in bleeding in patients with AF with ACS undergoing PCI (NCT04981041). Moreover, whether a precision medicine approach with a tailored selection of oral P2Y12 inhibitor in PCI patients requiring OAC can optimize outcomes is a topic of ongoing investigation.9 Novel therapeutics aimed at inhibiting factor XI (FXI), which has the potential to uncouple thrombosis from hemostasis, represents an area of ongoing investigation and be of potential interest for high bleeding and high ischemic risk patients, which may include patients with AF undergoing PCI.10 In summary, real-world registry data on antithrombotic treatment regimens being used among PCI patients also requiring OAC show patterns that are divergent from guideline recommendations, which may stem from differences in the complexity of patients being treated from those enrolled in clinical trials. Such divergences between guideline recommendations and real-world clinical practice are not novel.11 Real-world registries such as this by Sciahbasi et al are indeed informative to understand such discrepancies, not only to identify potential opportunities for improvement but also confirm strategies that reinforce findings from randomized trial data and others that may not. The latter may set the foundations for dedicated research in more complex clinical scenarios that will ultimately inform on the optimal management of these patients.