Could the PARIS Risk Scores Be Useful for the Choice of Triple versus Dual Antithrombotic Therapy in Patients with Atrial Fibrillation Undergoing Percutaneous Coronary Intervention?

Current guidelines and consensus documents recommend dual antithrombotic therapy (DAT; an oral anticoagulant plus one antiplatelet) for the majority of patients with atrial fibrillation (AF) undergoing percutaneous coronary intervention (PCI) and suggest a short course of triple antithrombotic therapy (TAT; an oral anticoagulant plus dual antiplatelet therapy) for those at very high risk for recurrent ischemic events but without features associated with major bleeding events [1, 2]. Nevertheless, because ischemic and hemorrhagic risks often share predictors, it can be difficult to identify the ideal antithrombotic strategy in daily practice. The Patterns of non-Adherence to Anti-Platelet Regimen in Stented Patients (PARIS) risk score has recently been developed and validated as a tool to help physicians in stratifying post-discharge coronary thrombotic risk (TR) and bleeding risk (BR) in patients with acute coronary syndromes (ACS) treated with PCI [3].

The aim of this analysis was to analyze if the PARIS ischemic-hemorrhagic scale could be useful in patients with ACS and concomitant AF treated with coronary stenting enrolled in the prospective, observational, nationwide Management of Antithrombotic TherApy in Patients with Chronic or DevelOping AtRial Fibrillation During Hospitalization for PCI (MATADOR-PCI) registry [4, 5].

The MATADOR-PCI study [4, 5] was aimed to assess the antithrombotic management and clinical events of patients with AF admitted to Italian cardiology intensive care units (CCUs) for an ACS and undergoing PCI with stent implantation. The design and the main results of the MATADOR-PCI registry have been published previously [4, 5]. Briefly, the MATADOR-PCI was a prospective, observational, nationwide registry conducted in 76 Italian cardiology intensive care units between August 2018 and December 2019. All consecutive patients with AF and a confirmed diagnosis of ACS [non-ST elevation-ACS or ST-elevation myocardial infarction] undergoing PCI with at least 1 stent implantation have been included [4, 5]. A clinical follow-up at 6 months was also planned for all patients.

Patients admitted with a diagnosis of ACS at the time of enrollment but not confirmed during hospitalization, ACS treated medically, with surgical revascularization or with percutaneous coronary balloon angioplasty without stent implantation, and those not giving informed consent were excluded from the survey [4, 5].

Data were collected using a Web-based, electronic CRF with the central database located at the Associazione Nazionale Medici Cardiologi Ospedalieri (ANMCO) Research Center. By using a validation plan, integrated in the data entry software, data were checked for missing or contradictory entries and values out of the normal range.

The PARIS scores were calculated according to the definitions used in the developmental cohort [3]. The PARIS scoring system ranged from 0 to 10 for coronary thrombotic events (definite or probable stent thrombosis and spontaneous myocardial infarction; MI) and from 0 to 14 points for major bleedings (grade 3 or 5, according to the classification of the Bleeding Academic Research Consortium; BARC). Therefore, it classifies patients into three risk strata for TR (low: 0–2, intermediate: 3–4, and high: ≥5 points) and BR (low: 0–3, moderate: 4–7, and high: ≥8 points) [3].

We assessed in our cohort the use of TAT and DAT at discharge and the rates of coronary thrombotic events (stent thrombosis and MI) and major bleedings (BARC 3 or 5) at 6-month follow-up, according to PARIS risk strata.

Seventy-six cardiology centers, well representing the Italian cardiology reality in terms of geographical distribution and level of hospital technology, participated in the study [4, 5]. Each site started patient enrollment after local IRB approval. Between August 2018 and December 2019, 598 consecutive patients have been enrolled: the mean age was 73 ± 10 years, 30% were female, 54% had a final diagnosis of non-ST elevation ACS, 42% had prior episodes of AF, 11% a history of stroke/TIA, 33% were diabetics, and 20% had a chronic kidney disease [4]. The mean CHA₂DS₂-VASc score was 3.3 ± 1.7, while the HAS-BLED was 2.3 ± 1.1. At the time of coronary angiography, a radial approach was used in 86% of cases and a multivessel disease was present in 51% of the population. PCI was performed on left anterior descending coronary artery in the majority of cases (55%) and a drug-eluting stent was implanted in 98% of patients.

Among the 588 patients discharged alive, a TAT was prescribed in 381 (64.8%) and DAT in 52 (8.8%) patients [4]. The use of TAT was more frequent in North and South versus Central (65.4%, 69.1%, 54.3%), while DAT was more used in Central versus North and South Italy (17.1%, 7.6%, 6.4%); p = 0.01. DAT was also more frequently uses in non-urban versus urban (15.9% vs. 4.9%; p < 0.0001) and in non-academic versus academic participating centers (9.6% vs. 3.0%; p = 0.01). Among patients discharged on DAT, acetylsalicylic acid was used in 7.7%, clopidogrel in 78.9%, and ticagrelor in 13.4% of cases; in the TAT group, clopidogrel was used in 98.2%, prasugrel in 0.3%, and ticagrelor in 1.5% of patients, in addition to acetylsalicylic acid. Direct oral anticoagulants were largely used in both patients receiving TAT (84.3%) and DAT (84.6%). According to the PARIS scoring system, 142 (24.2%) were classified as low, 244 (41.5%) as intermediate and 202 (34.3%) as high TR. In parallel, 87 (14.8%) were categorized into low, 260 (44.2%) in the intermediate, and 241 (41.0%) in the high-risk stratum for major bleedings. Crossing the various strata of the two PARIS risk scores, the largest group of patients consisted of those at high TR and BR (n = 130, 22%), followed by those at intermediate risk according to both scores (n = 122, 21%). At discharge, TAT was mainly used in patients at intermediate to high BR, while DAT in those at low BR, according to the PARIS score (Fig. 1).

At 6 months follow-up, the rates of thrombotic events (low: 0; intermediate: 0.8%; high: 2.0%; p = 0.18) and major bleedings (low: 1.2%; intermediate: 2.3%; high: 3.7%; p = 0.38) consistently increased, according to the PARIS strata.

The present analysis, including a nationwide, contemporary, real-world cohort of patients with concomitant ACS and AF, suggests that some known clinical variables associated with increased post-PCI TR or BR are poorly considered in the daily choice of antithrombotic strategies for ACS patients with concomitant AF.

Multiple guidelines and consensus documents have been published over the past decade to inform clinicians on the optimal antithrombotic strategy for AF patients undergoing PCI [1, 6, 7]. All documents agree in suggesting DAT as a default strategy, based on results of randomized trials that showed a more favorable safety profile compared with TAT [1, 6, 7]. However, the same documents indicate that TAT for up to 1 month can be considered in patients who have high TR and low BR [1, 6, 7]. Our data suggest that TAT is still largely used in Italy. These findings may be related to the ESC guidelines available during the conduction of our registry that did not consider all the recently published evidence [8], to the absence of updated hospital protocols, therapeutic inertia or to the lack of validated risk scores for the identification of patients who could benefit more from TAT or DAT. Indeed, the definition of the risk is not based on validated risk scores, as happens for the evaluation of the dual antiplatelet therapy duration after PCI, but on generic clinical factors that often overlap in the determination of the TR and BR. In this regard, the use of the PARIS scales, as proposed in this analysis, could help clinical judgment in properly identifying both patient risk and the ideal antithrombotic strategy at the time of discharge of patients with AF undergoing PCI.

Local Institutional Review Boards (IRBs) approved the study protocol according to the current Italian rules. The IRB of the coordinator center (A.O. San Camillo - Forlanini) approved the study on January 24th, 2018 (reference number: 151/CS). Written informed consent from participants was not required for the study presented in this article in accordance with local/national guidelines.

De Luca and Rubboli report lecture fees from Bayer, Boehringer Ingelheim, Daiichi Sankyo, and Pfizer/BMS outside the submitted work; all other authors have reported that no potential conflicts of interest exist with any companies/organizations whose products or services may be discussed in this article. Colivicchi is an Associate Editor of this journal. Lucci is an employee of Heart Care Foundation, which conducted the study with an unrestricted grant of research from Boehringer Ingelheim and Pharma GmbH & CoKG.

The sponsor of the study was the Heart Care Foundation, a non-profit independent organization, which also owns the database. Database management, quality control of the data, and data analyses were under the responsibility of the ANMCO Research Centre of the Heart Care Foundation. The study was partially supported by an unrestricted grant by Boehringer Ingelheim and Pharma GmbH & CoKG. No compensations were provided to participating sites, investigators, nor members of the Steering Committee. The Steering Committee of the study had full access to all the data in this study and takes complete responsibility for the integrity of the data and the accuracy of the data analysis.

The Steering Committee designed the study. All authors participated in the conduct of the study and contributed to the interpretation of the results. L.D.L., L.B., and A.R. drafted the manuscript; D.G., F.C., and M.M.G. revised it critically; D.L. analyzed the data.

Data are available upon reasonable request to ANMCO Research Center, Florence, Italy.

Clinical Trial Registration: URL, http://www.clinicaltrials.gov; unique identifier, NCT03656523.